A Randomized Study Comparing Blinatumomab Alternating With Low-intensity Chemotherapy Versus Standard of Care Chemotherapy for Older Adults With Newly Diagnosed Philadelphia-negative B-cell Precursor Acute Lymphoblastic Leukemia with Safety Run-in (Golden Gate Study)

Start 17 Feb 2022 · Status Ongoing, recruitment ended · 17 EU/EEA countries · 90 sites · Protocol 20190360

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)

Status Ongoing, recruitment ended

Participants planned 307

Countries 17

Sites 90

Newly diagnosed Philadelphia-negative B-cell precursor Acute Lymphoblastic Leukemia in older adults

Safety Run In (SRI): To evaluate the safety and tolerability of blinatumomab alternating with low-intensity chemotherapy Phase 3 (Ph3): To compare event-free survival (EFS) of subjects receiving blinatumomab alternating with low-intensity chemotherapy to EFS of subjects receiving standard of care (SOC) chemotherapy Ph…

Key facts

Sponsor: Amgen Inc.
Participant type: Patients
Age range: 18-64 years, 65+ years
Gender: Male and Female
Therapeutic area: Diseases [C] - Neoplasms [C04]
Trial duration: 17 Feb 2022 → ongoing
Decision date (initial): 2024-04-23
Transition trial: Yes
Low-intervention: No
Rare-disease indication: No
Vulnerable population: Yes
Funding sources: Amgen Inc.

External identifiers

EU CT number: 2023-503640-14-00
EudraCT number: 2020-004498-29
WHO UTN: U1111-1301-7654
ClinicalTrials.gov: NCT04994717

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety

Safety Run In (SRI): To evaluate the safety and tolerability of blinatumomab alternating with low-intensity chemotherapy
Phase 3 (Ph3): To compare event-free survival (EFS) of subjects receiving blinatumomab alternating with low-intensity chemotherapy to EFS of subjects receiving standard of care (SOC) chemotherapy
Ph3: To compare overall survival (OS) of blinatumomab alternating with low-intensity chemotherapy to SOC chemotherapy

Secondary objectives 16

SRI: To evaluate efficacy endpoints of blinatumomab alternating with low-intensity chemotherapy
SRI: To characterize the pharmacokinetics (PK) of blinatumomab alternating with low-intensity chemotherapy
Ph3: To compare patient-reported fatigues with blinatumomab alternating with low-intensity chemotherapy to SOC chemotherapy
Ph3: To compare patient-reported pain with blinatumomab alternating with low-intensity chemotherapy to SOC chemotherapy
Ph3: To compare additional patient-reported outcomes (PROs) and global health status as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQC30)
Ph3: To compare other efficacy endpoints of blinatumomab alternating with low-intensity chemotherapy to SOC chemotherapy
Ph3: To compare the safety of blinatumomab alternating with low-intensity chemotherapy to SOC chemotherapy
Ph3: To characterize relapses by cluster of differentiation (CD)19 expression, lineage switch and relapse localization in both treatment arms.
Ph3: To evaluate non-relapse mortality in both treatment arms
Ph3: To evaluate the proportion of allogeneic and autologous HSCT in continuous first CR after receiving blinatumomab alternating with low-intensity chemotherapy compared to SOC chemotherapy
Ph3: To evaluate non-relapse mortality following autologous and allogeneic HSCT in both treatment arms
Ph3: To evaluate relapse rate following autologous and allogeneic HSCT in both treatment arms
Ph3: To compare patient-reported fatigues with blinatumomab alternating with low-intensity chemotherapy to SOC chemotherapy
Ph3: To compare patient-reported pain with blinatumomab alternating with low-intensity chemotherapy to SOC chemotherapy
Ph3: To compare additional PROs and global health status as measured by the EORTC QLQ-C30
Ph3: To evaluate the PK of blinatumomab

Conditions and MedDRA coding

Newly diagnosed Philadelphia-negative B-cell precursor Acute Lymphoblastic Leukemia in older adults

Version	Level	Code	Term	System organ class
21.0	LLT	10000844	Acute lymphoblastic leukaemia	10029104

Study design 2 periods

#	Title	Allocation	Blinding	Roles blinded	Arms
1	Safety Run-in The safety run-in will be performed prior to initiating the phase 3 randomized part of the study. This safety run-in is to evaluate the safety and tolerability of blinatumomab alternating with low-intensity chemotherapy. The safety run-in also evaluates a shorter dose step interval from (4 days instead of 7 days) and a 1-week (instead of 2-week) drug free interval between blinatumomab cycles. Blinatumomab will be infused at a lower dose for 4 days and increase to a higher dose on Day 5 of the infusion for the remainder of the infusion. The safety run-in will enroll approximately 10 subjects and will include continuous adverse event monitoring, intensive pharmacokinetic (PK) and pharmacodynamic (PD) sampling	Not Applicable	None		Experimental: Safety Run-in: Blinatumomab alternating with low-intensity chemotherapy
2	Phase 3 Part The phase 3 part of the study aims to compare event-free survival (EFS) and overall survival (OS) of participants receiving blinatumomab alternating with low-intensity chemotherapy to EFS and (OS) of participants receiving standard of care (SOC) chemotherapy. In the phase 3 portion of the study, after completing the screening period, eligible subjects will be randomized 1:1 between the experimental arm consisting of blinatumomab alternating with low intensity chemotherapy versus SOC chemotherapy (GMALL regimen or hyperCVAD regimen). Approx. 274 subjects will be randomized in the phase 3 part of the study.	Randomised Controlled	None		Experimental Phase 3: Blinatumomab alternating with low-intensity chemotherapy: Participants will receive blinatumomab alternating with low-intensity chemotherapy. Active Comparator Phase 3: Standard of care (SOC) chemotherapy: Participants will receive 1 of 2 SOC chemotherapy regimens (GMALL or HyperCVAD) per investigator's choice.

Regulatory references

Scientific advice from competent authorities: European Medicines Agency
Plan to share IPD: Yes
IPD plan description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request. Information on IPD sharing Access Criteria, Time Frame and Supporting Information Type is available on ClinicalTrials.gov

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

Subject has provided informed consent prior to initiation of any study specific activities/procedures OR Where permitted by local law, subject’s legally acceptable representative has provided informed consent prior to any study-specific activities/procedures being initiated when the subject has any kind of condition that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent.
Age ≥ 55 years at the time of informed consent OR Age 40 to < 55 years of age if at least 1 of the following comorbidities at the time of informed consent: - history of grades 3 and 4 pancreatitis - diabetes mellitus with end-organ damage - severe liver disease such as cirrhosis stage 2 with portal hypertension or history of esophageal variceal bleeding and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 10 x upper limit of normal (ULN) (liver cirrhosis must be confirmed by biopsy) - body mass index (BMI) ≥ 40 combined with relevant comorbidities such as metabolic syndrome - Any further combination of documented severe comorbidities that the investigator judges to be incompatible with administering an intensive pediatric-based, adult adapted standard chemotherapy regimen but still compatible with the suggested protocol for older subjects in both the experimental and the SOC arm. The subject history needs to be reviewed by the medical monitor during screening to determine enrollment acceptability based on a standard list with types of comorbidities allowed.
Subjects with newly diagnosed Philadelphia (Ph)-negative B-cell precursor acute lymphoblastic leukemia (ALL) per WHO criteria
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, higher ECOG score allowed if due to underlying leukemia.
All subjects must have adequate organ function as defined below: - renal: estimated glomerular filtration rate based on Modification of Diet in Renal Disease (MDRD) calculation ≥ 50 mL/min/1.73 m2 - liver function: total bilirubin ≤ 2x upper limit of normal (ULN; unless Gilbert’s Disease or if liver involvement with leukemia); exception for subjects 40 to < 55 years of age if comorbidity is per inclusion 102: severe liver disease such as cirrhosis stage 2 with portal hypertension or history of esophageal variceal bleeding and AST/ALT >10 x ULN (liver cirrhosis must be confirmed by biopsy) - cardiac: left ventricular ejection fraction (LVEF) ≥ 50% and no clinically significant, uncontrolled, or active cardiovascular disease (eg, myocardial infarction or stroke within 3 months). Consult with medical monitor as needed.

Exclusion criteria 9

Active CNS leukemia (i.e, CNS 3 leukemia, confirmed by lumbar puncture) not resolved with IT chemotherapy during screening
History of other malignancy within the past 3 years, with the following exceptions: - Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before enrollment and felt to be at low risk for recurrence by the treating physician. - Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. - Adequately treated cervical carcinoma in situ without evidence of disease. - Adequately treated breast ductal carcinoma in situ without evidence of disease. - Prostatic intraepithelial neoplasia without evidence of prostate cancer. - Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ.
History or presence of clinically relevant CNS pathology or eventsuch as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's diease, cerebellar disease, organic brain syndrome, or psychiatric conditions that preclude the use of high dose of corticosteroids. Consult with medical monitor as needed.
Current autoimmune disease or history of autoimmune disease with potential CNS involvement
Known infection with human immunodeficiency virus (HIV)
Known infection with chronic or active hepatitis B (eg, hepatitis b surface [HBs] antigen reactive or quantifiable hepatitis b virus [HBV] viral load) or hepatitis C virus (HCV) (eg, HCV RNA [qualitative] is detected). Active hepatitis B and C based on the following results: - Positive for hepatitis B surface antigen (HepBsAg) (indicative of chronic hepatitis B or recent acute hepatitis B) - Negative HepBsAg and positive for hepatitis B core antibody: negative HBV DNA by PCR result is necessary to enroll. - Positive Hepatitis C virus antibody (HepCAb): negative hepatitis C virus RNA by PCR result is necessary to enroll.
Subject with symptoms and/or clinical signs and/or radiographic and/or sonographic signs that indicate an acute or uncontrolled chronic infection.
Cancer chemotherapy for this newly diagnosed B cell ALL before the start of protocol-required therapy with the exception of IT chemotherapy or pre-phase chemotherapy. Radiation to a spot lesion such as chloroma or lytic lesion of bone or vertebrae for pain or vertebral stabilization is allowed.
Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

SRI: Treatment-emergent adverse events, treatment-related adverse events, and adverse events of interest
Ph3: EFS: time from randomization until treatment failure, relapse, or death from any cause, whichever is earlier. Subjects without an event will be censored at their last evaluable disease assessment date.
Ph3: OS: time from randomization until death due to any cause. Subjects alive will be censored at the date last known to be alive.

Secondary endpoints 30

SRI: Complete remission (CR) by the end of the initial disease assessment period
SRI: Minimal residual disease (MRD) response < 10-4 by the end of the initial disease assessment period
SRI: Relapse-free survival (RFS): in subjects who achieve CR, the time from first achievement of this response until date of the first relapse including hematologic relapse, extramedullary relapse, or death due to any cause, whichever occurs first. Subjects without an event will be censored at their last evaluable disease assessment date.
SRI: MRD RFS in subjects who achieve CR with MRD response, the time from first achievement of this response until date of the first relapse including molecular relapse, hematologic relapse, and/or extramedullary relapse, or death due to any cause, whichever occurs first. Molecular relapse will be defined 2 ways: MRD ≥ 10-3 and MRD 10-4. Subjects without an event will be censored at their last evaluable disease assessment date.
SRI: PK parameters for blinatumomab including, but not limited to, steady state concentration (Css) and clearance (CL)
Ph3: Change from baseline to end of the initial disease assessment period in fatigue score measured by Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue – Short Form 7a
Ph3: Change from baseline to end of the initial disease assessment period in pain score measured by Brief Pain Inventory – Short Form (BPI-SF); Item 3: pain at its worst in the last 24 hours
Ph3: Change from baseline to end of the initial disease assessment period in global health status measured by the QLQ-C30 global health status quality of life scale
Ph3: Change from baseline to end of the initial disease assessment period in physical function measured by the QLQ-C30 functional scale
Ph3: Change from baseline to end of the initial disease assessment period in nausea/vomiting measured by the QLQ-C30 symptom scale
Ph3: CR by the end of the initial disease assessment period
Ph3: MRD response < 10-4 by the end of the initial disease assessment period
Ph3: RFS: in subjects who achieve CR, the time from first achievement of this response until date of the first relapse including hematologic relapse, extramedullary relapse, or death due to any cause, whichever occurs first. Subjects without an event will be censored at their last evaluable disease assessment date.
Ph3: MRD RFS in subjects who achieve CR with MRD response, the time from first achievement of this response until date of the first relapse including molecular relapse, hematologic relapse, and/or extramedullary relapse, or death due to any cause, whichever occurs first. Molecular relapse will be defined 2 ways: MRD ≥ 10-3 and MRD 10-4. Subjects without an event will be censored at their last evaluable disease assessment date.
Ph3: MRD level over time
Ph3: treatment-emergent adverse events, treatment related adverse events, and adverse events of interest
Ph3: CD19 positive relapse and CD19 negative relapse identified by flow cytometry or immunocytochemistry for bone marrow (mandatory)
Ph3: CD19 positive relapse and CD19 negative relapse identified by flow cytometry or immunohistochemistry for cerebrospinal fluid (mandatory)
Ph3: CD19 positive relapse and CD19 negative relapse for extramedullary sites other than cerebrospinal fluid (optional - if data is available)
Ph3: Lineage switch to acute myeloid leukemia (AML)
Ph3: Localization of relapse by clinical assessment
Ph3: Mortality in CR
Ph3: Autologous and allogeneic HSCT in continuous first CR*
Ph3: Mortality in CR after autologous and allogeneic HSCT*
Ph3: Relapse after autologous and allogeneic HSCT
Ph3: Time to deterioration and time to improvements for fatigue score measured by PROMIS Fatigue – Short Form 7a
Ph3: Time to deterioration and time to improvements for pain score measured by BPI-SF; Item 3: pain at its worst in the last 24 hours
Ph3: Change from baseline in all other subscales of QLQ-C30 (role, cognitive, emotional, and social scales; pain and fatigue scales; single items: dyspnea, loss of appetite, insomnia, constipation, diarrhea, and perceived financial impact)
Ph3: Time to deterioration and time to improvements for global health status, physical function, and nausea/vomiting scales.
Ph3: Css and CL

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 10

Blinatumomab

SUB35403 · Substance

Active substance: Blinatumomab
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENOUS USE
Max daily dose: 28 µg microgram(s)
Max total dose: 5355 µg microgram(s)
Max treatment duration: 28 Week(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: Yes
Orphan designation number: EU/3/09/650
Modified vs. Marketing Authorisation: No

Methotrexate Sodium

SUB03225MIG · Substance

Active substance: Methotrexate Sodium
Pharmaceutical form: SOLUTION FOR INJECTION
Route of administration: INTRAVENOUS USE
Max daily dose: 1 mg/m2 milligram(s)/square meter
Max total dose: 2250 mg/m2 milligram(s)/square meter
Max treatment duration: 3 Day(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Methotrexate Sodium

SUB03225MIG · Substance

Active substance: Methotrexate Sodium
Pharmaceutical form: TABLET
Route of administration: ORAL USE
Max daily dose: 20 mg/m2 milligram(s)/square meter
Max total dose: 960 mg/m2 milligram(s)/square meter
Max treatment duration: 48 Day(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Mercaptopurine

SUB12149MIG · Substance

Active substance: Mercaptopurine
Pharmaceutical form: TABLETS
Route of administration: ORAL USE
Max daily dose: 60 mg/m2 milligram(s)/square meter
Max total dose: 20160 mg/m2 milligram(s)/square meter
Max treatment duration: 48 Week(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Cyclophosphamide

SUB06859MIG · Substance

Active substance: Cyclophosphamide
Pharmaceutical form: POWDER FOR SOLUTION FOR INJECTION
Route of administration: INTRAVENOUS
Max daily dose: 150 mg/m2 milligram(s)/square meter
Max total dose: 900 mg/m2 milligram(s)/square meter
Max treatment duration: 6 Day(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Cytarabine

SUB06880MIG · Substance

Active substance: Cytarabine
Pharmaceutical form: SOLUTION FOR INJECTION/INFUSION
Route of administration: INTRAVENOUS USE
Max daily dose: 1000 mg/m2 milligram(s)/square meter
Max total dose: 2000 mg/m2 milligram(s)/square meter
Max treatment duration: 2 Day(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Rituximab

SUB12570MIG · Substance

Active substance: Rituximab
Pharmaceutical form: CONCENTRATE FOR SOLUTION FOR INFUSION
Route of administration: INTRAVENOUS USE
Max daily dose: 375 mg/m2 milligram(s)/square meter
Max total dose: 3000 mg/m2 milligram(s)/square meter
Max treatment duration: 8 Day(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Vincristine Sulfate

SUB05101MIG · Substance

Active substance: Vincristine Sulfate
Pharmaceutical form: SOLUTION FOR INJECTION/INFUSION
Route of administration: INTRAVENOUS USE
Max daily dose: 8 mg milligram(s)
Max total dose: 2 mg milligram(s)
Max treatment duration: 4 Day(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Dexamethasone

SUB07017MIG · Substance

Active substance: Dexamethasone
Pharmaceutical form: SOLUTION FOR INJECTION
Route of administration: INTRAVENOUS USE
Max daily dose: 10 mg/m2 milligram(s)/square meter
Max total dose: 40 mg/m2 milligram(s)/square meter
Max treatment duration: 4 Day(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Dexamethasone

SUB07017MIG · Substance

Active substance: Dexamethasone
Pharmaceutical form: TABLET
Route of administration: ORAL USE
Max daily dose: 10 mg/m2 milligram(s)/square meter
Max total dose: 40 mg/m2 milligram(s)/square meter
Max treatment duration: 4 Day(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Comparator 17

Asparaginase

SUB12950MIG · Substance

Active substance: Asparaginase
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENOUS USE
Max daily dose: 6000 U unit(s)
Max total dose: 162000 U unit(s)
Max treatment duration: 27 Day(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Mercaptopurine

SUB12149MIG · Substance

Active substance: Mercaptopurine
Pharmaceutical form: TABLETS
Route of administration: ORAL USE
Max daily dose: 60 mg/m2 milligram(s)/square meter
Max total dose: 50400 mg/m2 milligram(s)/square meter
Max treatment duration: 120 Week(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Rituximab

SUB12570MIG · Substance

Active substance: Rituximab
Pharmaceutical form: CONCENTRATE FOR SOLUTION FOR INFUSION
Route of administration: INTRAVENOUS USE
Max daily dose: 375 mg/m2 milligram(s)/sq. meter
Max total dose: 3000 mg/m2 milligram(s)/sq. meter
Max treatment duration: 8 Day(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Crisantaspase

SUB33789 · Substance

Active substance: Crisantaspase
Pharmaceutical form: POWDER FOR SOLUTION FOR INJECTION/INFUSION
Route of administration: INTRAVENOUS USE
Max daily dose: 50 mg/m2 milligram(s)/square meter
Max total dose: 3600 mg/m2 milligram(s)/square meter
Max treatment duration: 36 Day(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Idarubicin

SUB08111MIG · Substance

Active substance: Idarubicin
Pharmaceutical form: POWDER FOR SOLUTION FOR INJECTION
Route of administration: INTRAVENOUS USE
Max daily dose: 10 mg milligram(s)
Max total dose: 70 mg milligram(s)
Max treatment duration: 7 Day(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Prednisone

SUB10020MIG · Substance

Active substance: Prednisone
Pharmaceutical form: TABLET
Route of administration: ORAL USE
Max daily dose: 200 mg milligram(s)
Max total dose: 30000 mg milligram(s)
Max treatment duration: 150 Day(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Methotrexate Sodium

SUB03225MIG · Substance

Active substance: Methotrexate Sodium
Pharmaceutical form: SOLUTION FOR INJECTION
Route of administration: INTRAVENOUS USE
Max daily dose: 1 mg/m2 milligram(s)/square meter
Max total dose: 12 mg/m2 milligram(s)/square meter
Max treatment duration: 6 Day(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Methotrexate Sodium

SUB03225MIG · Substance

Active substance: Methotrexate Sodium
Pharmaceutical form: TABLET
Route of administration: ORAL USE
Max daily dose: 20 mg milligram(s)
Max total dose: 2400 mg milligram(s)
Max treatment duration: 120 Day(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Prednisolone

SUB10018MIG · Substance

Active substance: Prednisolone
Pharmaceutical form: TABLET
Route of administration: ORAL USE
Max daily dose: 200 mg milligram(s)
Max total dose: 30000 mg milligram(s)
Max treatment duration: 150 Day(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Vincristine Sulfate

SUB05101MIG · Substance

Active substance: Vincristine Sulfate
Pharmaceutical form: SOLUTION FOR INJECTION/INFUSION
Route of administration: INTRAVENOUS USE
Max daily dose: 2 mg milligram(s)
Max total dose: 76 mg milligram(s)
Max treatment duration: 36 Day(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Cytarabine

SUB06880MIG · Substance

Active substance: Cytarabine
Pharmaceutical form: SOLUTION FOR INJECTION/INFUSION
Route of administration: INTRAVENOUS USE
Max daily dose: 60 mg/m2 milligram(s)/square meter
Max total dose: 840 mg/m2 milligram(s)/square meter
Max treatment duration: 12 Day(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Pegaspargase

SUB03666MIG · Substance

Active substance: Pegaspargase
Pharmaceutical form: SOLUTION FOR INJECTION/INFUSION
Route of administration: INTRAVENOUS USE
Max daily dose: 1000 U unit(s)
Max total dose: 6000 U unit(s)
Max treatment duration: 6 Day(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Doxorubicin

SUB06391MIG · Substance

Active substance: Doxorubicin
Pharmaceutical form: CONCENTRATE FOR SOLUTION FOR INFUSION
Route of administration: INTRAVENOUS USE
Max daily dose: 50 mg/m2 milligram(s)/square meter
Max total dose: 200 mg/m2 milligram(s)/square meter
Max treatment duration: 4 Day(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Dexamethasone

SUB07017MIG · Substance

Active substance: Dexamethasone
Pharmaceutical form: TABLET
Route of administration: ORAL USE
Max daily dose: 40 mg/m2 milligram(s)/square meter
Max total dose: 1280 mg/m2 milligram(s)/square meter
Max treatment duration: 12 Day(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Dexamethasone

SUB07017MIG · Substance

Active substance: Dexamethasone
Pharmaceutical form: SOLUTION FOR INJECTION
Route of administration: INTRAVENOUS USE
Max daily dose: 40 mg milligram(s)
Max total dose: 1280 mg milligram(s)
Max treatment duration: 32 Day(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Blinatumomab

SUB35403 · Substance

Active substance: Blinatumomab
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENOUS USE
Max daily dose: 28 µg microgram(s)
Max total dose: 448 µg microgram(s)
Max treatment duration: 16 Week(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: Yes
Orphan designation number: EU/3/09/650
Modified vs. Marketing Authorisation: No

Cyclophosphamide

SUB06859MIG · Substance

Active substance: Cyclophosphamide
Pharmaceutical form: POWDER FOR SOLUTION FOR INJECTION
Route of administration: INTRAVENOUS USE
Max daily dose: 500 mg/m2 milligram(s)/square meter
Max total dose: 1200 mg/m2 milligram(s)/square meter
Max treatment duration: 12 Day(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amgen Inc.

Sponsor organisation: Amgen Inc.
Address: 1 Amgen Center Drive
City: Thousand Oaks
Postcode: 91320-1799
Country: United States

Scientific contact point

Organisation: Amgen Inc.
Contact name: Medical Information

Public contact point

Organisation: Amgen Inc.
Contact name: Medical Information

Third parties 14

Organisation	City, country	Duties
Amgen Research (Munich) GmbH ORG-100008176	Munich, Germany	Laboratory analysis
Adaptive Biotechnologies Corp. ORG-100044428	Seattle, United States	Laboratory analysis
Excelya Greece CRO Single Member S.A. ORG-100009224	Nea Filadelfia, Greece	On site monitoring, Other
Amgen Limited ORG-100008433	Uxbridge, United Kingdom	Laboratory analysis
Fortrea Inc. ORG-100012602	Bannockburn, United States	Other
Almac Clinical Technologies LLC ORG-100043036	Souderton, United States	Interactive response technologies (IRT)
Labcorp Central Laboratory Services SARL ORG-100011524	Meyrin, Switzerland	Other
The Childrens Hospital Los Angeles ORG-100048201	Los Angeles, United States	Laboratory analysis
Universitaetsklinikum Schleswig-Holstein AöR ORG-100023619	Kiel, Germany	Laboratory analysis
Altasciences Compagnie Inc. ORG-100037610	Laval, Canada	Laboratory analysis
Signant Health LLC ORG-100040732	Blue Bell, United States	Other
Amgen Inc. ORG-100002102	Thousand Oaks, United States	Laboratory analysis
Eurofins Panlabs Inc. ORG-100044318	Saint Charles, United States	Laboratory analysis
Q Squared Solutions Limited ORG-100042527	Reading, United Kingdom	Laboratory analysis

Locations

17 EU/EEA countries · 90 investigational sites

By country

Country	MS status	Planned subjects	Sites
Austria	Ended	4	4
Belgium	Ongoing, recruitment ended	14	10
Bulgaria	Ongoing, recruitment ended	2	1
Czechia	Ongoing, recruitment ended	3	3
Denmark	Ongoing, recruitment ended	8	4
Estonia	Ended	2	2
Finland	Ongoing, recruitment ended	5	2
France	Ongoing, recruitment ended	50	14
Greece	Ongoing, recruitment ended	10	8
Hungary	Ongoing, recruitment ended	5	6
Italy	Ongoing, recruitment ended	34	13
Netherlands	Ongoing, recruitment ended	3	1
Portugal	Ongoing, recruitment ended	6	5
Romania	Ongoing, recruitment ended	8	6
Slovakia	Authorised, recruiting	2	2
Spain	Ongoing, recruitment ended	14	8
Sweden	Ongoing, recruitment ended	3	1
Rest of world Canada, United States, Mexico, Taiwan, Switzerland, Australia, United Kingdom, Japan, Turkey	—	134	—

Investigational sites

Austria

4 sites · Ended

Medizinische Universitaet Innsbruck

Department if Internal Medicine V, Hematology & Oncology, Anichstrasse 35, 6020, Innsbruck

Hanusch Krankenhaus Der Wiener Gebietskrankenkasse

3. Medical Department - Hematology and Oncoloy, Heinrich-Collin-Strasse 30/1100, Penzing, Vienna

Medical University Of Graz

Department of Internal Medicine, Division of Hematology, Neue Stiftingtalstrasse 6, 8010, Graz

Ordensklinikum Linz GmbH

Department of Hematology, hemostaseology and medical oncology; Hemato-oncological center, Fadingerstrasse 1, 4020, Linz

Belgium

10 sites · Ongoing, recruitment ended

Jessa Ziekenhuis

Hematology, Salvatorstraat 20, 3500, Hasselt

Institut Jules Bordet

Hematology, Mijlenmeersstraat 90, 1070, Anderlecht

Grand Hopital De Charleroi

Hematologie, Grand'rue 3, 6000, Charleroi

Az St-Jan Brugge-Oostende A.V.

Hematology, Ruddershove 10, 8000, Brugge

Algemeen Ziekenhuis Delta

Hematology, Deltalaan 1, 8800, Roeselare

Universitair Ziekenhuis Gent

Hematology, Corneel Heymanslaan 10, 9000, Gent

Cliniques Universitaires Saint-Luc

Hematology, Hippokrateslaan 10, Batiment 54, Sint-Lambrechts-Woluwe

Antwerp University Hospital

Hematology, Drie Eikenstraat 655, 2650, Edegem

Cabinet Medical Van Houte Cornejo Montero

Hematology, Avenue Dr-Gaston-Therasse 1, 5530, Yvoir

Centre hospitalier universitaire de Liege

Hematology, Avenue De L'hopital 1, 4000, Liege

Bulgaria

1 site · Ongoing, recruitment ended

University Multiprofile Hospital For Active Treatment Saint Georgi EAD

Clinic of Clinical Hematology, Bulevard Vasil Aprilov 15a, 4002, Plovdiv

Czechia

3 sites · Ongoing, recruitment ended

Fakultni Nemocnice Brno

Interni hematologicka a onkologicka klinika, Jihlavska 340/20, Bohunice, Brno

Fakultni Nemocnice Hradec Kralove

IV. Interni hematologicka klinika, Sokolska 581, Novy Hradec Kralove, Hradec Kralove

Ustav Hematologie A krevni Transfuze

Ustav hematologie a krevni transfuze, Katerinska 521/19, Nove Mesto, Prague 2

Denmark

4 sites · Ongoing, recruitment ended

Odense University Hospital

Hematology, J B Winsloews Vej 4, 5000, Odense C

Rigshospitalet

Hematology, Blegdamsvej 9, 2100, Copenhagen Oe

Aalborg University Hospital

Hematology, Moelleparkvej 4, 9000, Aalborg

Region Midtjylland

Hematology, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N

Estonia

2 sites · Ended

North Estonia Medical Centre Foundation

North Estonia Medical Centre, J. Sutiste Tee 19, Mustamae Linnaosa, Tallinn

Tartu University Hospital

Department of Haematology and Bone Marrow Transplantation, A006, L. Puusepa Tn 8, Tartu Linn

Finland

2 sites · Ongoing, recruitment ended

Turku University Hospital

Hematology, Hameentie 11, 20520, Turku

HUS-Yhtymae

Hematology, Haartmaninkatu 4, 00290, Helsinki

France

14 sites · Ongoing, recruitment ended

Institut Paoli-Calmettes

Service Hematologie, 232 Boulevard De Sainte Marguerite, Bp 156, Marseille

Centre Hospitalier Universitaire De Dijon

Service hematologie clinique, 14 Rue Paul Gaffarel, 21000, Dijon

Centre Hospitalier Universitaire De Nice

Service Hématologie, 151 Route De Saint Antoine, 06200, Nice

Centre Hospitalier Universitaire De Rennes

Hematologie, 2 Rue Henri Le Guilloux, 35000, Rennes

Centre Hospitalier De Versailles

Hematologie, 177 Rue De Versailles, 78150, Le Chesnay-Rocquencourt

Centre Hospitalier Universitaire De Lille

Service des Maladies du Sang, Rue Michel Polonowski, 59000, Lille

Institut Universitaire Du Cancer Toulouse-Oncopole

Service Hématologie, 1 Avenue Irene Joliot Curie, 31059, Toulouse Cedex 9

CHRU De Nancy

Service Hematologie et Medecine Interne, Rue Du Morvan, 54500, Vandoeuvre Les Nancy

Centre Hospitalier Lyon Sud

Hematology, 165 Chemin Du Grand Revoyet, 69310, Pierre-Benite

Hopital Saint Louis

Service des Maladies du Sang, 1 Avenue Claude Vellefaux, 75010, Paris

Hopital Saint Antoine

Service Hematologie Oncologie, 184 Rue Du Faubourg Saint Antoine, 75571, Paris Cedex 12

Hospital Hotel Dieu

Service Hematologie, 1 Place Alexis Ricordeau, 44000, Nantes

Assistance Publique Hopitaux De Paris

Service Hematologie, 51 Avenue Du Mal De Lattre De Tassigny, 94010, Creteil Cedex

University Hospital Of Bordeaux

Service Hematologie Clinique, 66 Avenue De Magellan, 33608, Pessac Cedex

Greece

8 sites · Ongoing, recruitment ended

General University Hospital Of Larissa

University Hematology Clinic, P. O. Box 1425, 411 10, Larissa

General University Hospital Of Patras

Bone Marrow Transplantation Unit, Rio, 265 04, Patras

University General Hospital Of Heraklion

Hematology Clinic, Stavrakia And Voutes, 715 00, Heraklion

Evangelismos S.A.

Hematology and Lymphoma Clinic, Ipsiladou 45-47, 106 76, Athens

Laiko General Hospital Of Athens

Hematology Clinic, Agiou Thoma (goudi) 17, 115 27, Athens

Geniko Nosokomeio Thessalonikis George Papanikolaou

Hematology Clinic and Bone Marrow Transplantation Unit, Exochi, 570 10, Thessaloniki

University General Hospital Of Ioannina

Hematology Clinic, Niarchou Stavrou Avenue, 455 00, Ioannina

University General Hospital Attikon General Hospital Of West Attica H Agia Varvara

2nd Department of Internal Medicine, Rimini 1, 124 61, Chaidari

Hungary

6 sites · Ongoing, recruitment ended

Semmelweis University

Belgyogyaszati es Hematologiai Klinika, Szentkiralyi Utca 46, VIII Kerulet, Budapest VIII

Del-Pesti Centrumkorhaz Orszagos Hematologiai Es Infektologiai Intezet

Haematologiai es Ossejt-transzplantacios Osztaly, Albert Florian Ut 5-7, 1097, Budapest IX

Szabolcs-Szatmar-Bereg Varmegyei Oktatokorhaz

Nyiregyhazi Josa Andras Tagkorhaz, Hematologia Osztaly, Szent Istvan Utca 68, 4400, Nyiregyhaza

Heves Varmegyei Markhot Ferenc Oktatokorhaz Es Rendelointezet

Belgyogyaszati Infektologiai Centrum, Belgyogyaszati Osztaly, Knezich Karoly Utca 1, 3300, Eger

University Of Szeged

Belgyogyaszati Klinika, Hematologia Centrum, Semmelweis Utca 8, 6725, Szeged

University Of Debrecen

Belgyogyaszati Klinika Hematologiai Tanszek, Nagyerdei Korut 98, 4032, Debrecen

Italy

13 sites · Ongoing, recruitment ended

Azienda Ulss 3 Serenissima

Ematologia, Mestre-Venezia, Via Don Federico Tosatto 147, Venice

IRCCS Ospedale Policlinico San Martino

Ematologia, Largo Rosanna Benzi 10, 16132, Genoa

Azienda Ospedaliera Universitaria Integrata Verona

Ematologia e Centro Trapianti Midollo Osseo, Piazzale Ludovico Antonio Scuro 10, 37134, Verona

Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino

Struttura Complessa Ematologia, Corso Bramante 88, 10126, Turin

Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico

Ematologia L e A Seragnoli, Via Pietro Albertoni 15, 40138, Bologna

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Ematologia, Via Francesco Sforza 28, 20122, Milan

Azienda Sanitaria Locale Di Pescara

Ematologia Clinica, Via Renato Paolini 47, 65124, Pescara

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII

Ematologia, Piazza Oms 1, 24127, Bergamo

Azienda Ospedaliero-Universitaria Policlinico Umberto I

Dipartimento di Biotecnologie Cellulari ed Ematologia, Viale Del Policlinico 155, 00161, Rome

Hospital Santa Maria Della Misericordia

Ematologia e Trapianto Midollo Osseo, Piazzale Giorgio Menghini 1, 06129, Perugia

Azienda Ospedaliera Di Rilievo Nazionale Antonio Cardarelli

Ematologia con Trapianto di Midollo Osseo, Via Antonio Cardarelli 9, 80131, Naples

University Hospital Consorziale Policlinico

Ematologia con Trapianto, Piazzale Giulio Cesare 11, 70124, Bari

Ospedale Vito Fazzi Lecce

Ematologia e Trapianto di cellule staminali, Piazza Filippo Muratore 1, 73100, Lecce

Netherlands

1 site · Ongoing, recruitment ended

Universitair Medisch Centrum Groningen

Hematology, Hanzeplein 1, 9713 GZ, Groningen

Portugal

5 sites · Ongoing, recruitment ended

Instituto Portugues De Oncologia De Lisboa Francisco Gentil E.P.E.

Serviço de Hematologia Clínica, Rua Professor Lima Basto, 1099-023, Lisbon

Centro Hospitalar E Universitario De Coimbra E.P.E.

Serviço de Oncologia Médica, Praceta Professor Mota Pinto, 3000-459, Coimbra

Instituto Portugues De Oncologia Do Porto Francisco Gentil E.P.E.

Serviço de Onco-Hematologia, Rua Dr. Antonio Bernardino De Almeida, 4200-072, Porto

Unidade Local De Saude De Santa Maria E.P.E.

Serviço de Hematologia Oncologica, Avenida Professor Egas Moniz, 1649-035, Lisbon

Centro Hospitalar Universitario Lisboa Central E.P.E.

Serviço de Hematologia, Rua Jose Antonio Serrano, 1150-199, Lisbon

Romania

6 sites · Ongoing, recruitment ended

Institute Of Oncology Prof. Dr. Ion Chiricuta Cluj-Napoca

Hematology, Strada Republicii 34-36, 400015, Cluj-Napoca

Institutul Clinic Fundeni

Hematology, Soseaua Fundeni 258, 022328, Bucharest

Spitalul Universitar De Urgenta Bucuresti

Hematology, Splaiul Independentei 169, 050098, Bucharest

Spitalul Clinic Judetean De Urgenta Sibiu

Hematology, Bulevardul Coposu Corneliu 2-4, 550245, Sibiu

Spitalul Clinic Municipal Filantropia Craiova

Hematology, Strada Filantropiei No 1, 200143, Craiova

Institutul Regional De Oncologie Iasi

Hematology, Strada G-Ral Berthelot 2-4, 700483, Iasi

Slovakia

2 sites · Authorised, recruiting

University Hospital Bratislava

klinika hematológie a transfuziológie, Antolska 11, Petrzalka, Bratislava

Narodny Onkologicky Ustav

Oddelenie Onkohematologie II, Klenova 1, Nove Mesto, Bratislava

Spain

8 sites · Ongoing, recruitment ended

Hospital Universitario Marques De Valdecilla

Servicio de Hematologia, Avenida Valdecilla Sn, 39008, Santander

Hospital Universitario Y Politecnico La Fe

Servicio de Hematologia, Avenida De Fernando Abril Martorell 106, 46026, Valencia

Hospital Universitario 12 De Octubre

Servicio de Hematologia, Avenida De Cordoba Sn, 28041, Madrid

Institut Catala D'oncologia

Servicio de Hematologia Clinica, Carretera Canyet S/n, 08916, Badalona

Hospital Universitari Vall D Hebron

Servicio de Hematologia, Edificio Materno-Infantil, Passeig De La Vall D'hebron 119-129, Barcelona

Hospital Universitario De Salamanca

Servicio de Hematologia, Paseo De San Vicente 58-182, 37007, Salamanca

Hospital General Universitario Reina Sofia

Servicio de Hematologia, Avenida Menendez Pidal S/n, 14004, Cordoba

Institut Catala D'oncologia

Servicio de Hematologia Clinica, Avinguda De La Gran Via De L'hospitalet 199-203, 08908, L'hospitalet De Llobregat

Sweden

1 site · Ongoing, recruitment ended

Sahlgrenska University Hospital-Vastra Gotalandsregionen

Department of Internal Medicine, Bla Straket 5, 413 46, Goteborg

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country	Trial start	Trial end	Recruitment start	Recruitment end
Austria	2023-09-20	2025-02-28	2024-01-22	2025-02-28
Belgium	2023-07-04		2023-07-26	2025-10-01
Bulgaria	2023-07-19		2024-05-20	2026-01-16
Czechia	2025-06-24		2025-08-18	2026-05-11
Denmark	2023-05-10		2023-12-11	2026-01-23
Estonia	2025-07-10
Finland	2023-10-12		2024-04-19	2026-05-11
France	2023-06-12		2023-06-29	2026-05-11
Greece	2023-07-18		2024-01-31	2026-05-11
Hungary	2023-04-26		2023-05-16	2026-05-11
Italy	2023-05-19		2023-08-31	2026-05-11
Netherlands	2023-11-17		2024-05-16	2025-07-01
Portugal	2023-10-10		2023-12-15	2026-05-11
Romania	2023-06-21		2023-07-31	2025-12-23
Slovakia	2025-07-04
Spain	2022-02-17		2023-05-29	2025-06-01
Sweden	2023-10-12		2024-02-27	2025-12-22

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Serious breach SB-85765

Sponsor became aware: 2025-05-30
Date of breach: 2025-05-16
Submission date: 2025-09-01
Member states concerned: Austria, Belgium, Bulgaria, Denmark, Finland, France, Greece, Hungary, Italy, Portugal, Romania, Spain, Sweden, Netherlands, Czechia, Estonia, Slovakia
Categories: Protocol
Areas impacted: Subject safety
Benefit-risk balance changed: No
Description: Brief description of the serious breach
This is a single occurrence of an infusion rate issue (2 times expected rate) with a centrally
provisioned QCore Sapphire pump during subject 36049004301 cIV blinatumomab Induction cycle 1.
Subject experienced events of low-grade fever (grade 1) and mild distal tremors in hands (grade 1)
for a duration of 1 day and was hospitalized (16May-20May2025) as a precaution as the events
occurred on a Friday and the PI wanted to closely monitor the patient over the weekend. Additionally,
blood cultures were obtained and the patient received empiric antibiotics until culture results were
available. After discharge, the subject resumed treatment with cIV blinatumomab on 02Jun2025
(Induction Cycle 2).
Sponsor actions: Impact assessment
Subject-level impact: Subject experienced events of low-grade fever (grade 1) and mild distal
tremors in hands (grade 1) for a duration of 1 day and was hospitalized as a precaution for
monitoring (16-20May2025). After discharge, the subject resumed treatment with cIV blinatumomab
on 02Jun2025 (Induction Cycle 2).
Study-level impact: no impact on other subjects in the study.
While the root cause investigation is ongoing, the sponsor cannot rule out a possible pump
malfunction. The concerned pump has been isolated and is no longer in use. With the current
information, there is no reason to believe that other pumps may pose a risk to the patients (no field
safety notices/alerts from the manufacturer, all pumps are regularly serviced and calibrated, pumps
used multiple times in the last few months at various sites/countries/patients without any untoward
events).
To date, there has been no occurrence of pump failure on this study or on prior cIV blinatumomab
studies. On this study, 132 subjects have received blinatumomab, with an average number of total
dosing days for each subject = 100.2 and an average number of total infusions for each subject =
15.5.
Program-level impact: no impact on other cIV blinatumomab studies in the program.
Root cause Investigation:
The root cause investigation for this incident is ongoing. No root cause has been determined yet.
To support determining the root cause for this incident, the Pump internal Event log is to be
downloaded and analyzed by the manufacturer to provide an understanding of the pump settings and
any change of pump settings over time. A pump physical examination by the manufacturer is also
required to confirm any mechanical and/or electronic failure. As of 4Jun2025, the pump return
process from site to manufacturer is ongoing.
Principal Investigator confirmed site procedures as adequate and followed. Site staff training on use
of pump was up to date prior before the subject starting treatment. The pump calibration was current,
and all previous infusions were completed without any issues. Interactions with the PI since the
incident have not been able to fully determine the pump settings – the manufacturer’s investigation
will clarify this.
Correction and preventative actions:
Immediate actions: 16May25 the patient was hospitalized and the blinatumomab infusion was
stopped. The patient was disconnected from the pump, and the pump was isolated from use. The
infusion bag was sent to the pharmacy to investigate the remaining volume to assess dosage given.
The patient recovered the same day as the events started (16May2025) but remained hospitalized as
a precaution until 20May25. The PI stated that since the events occurred on a Friday, the PI wanted
to closely monitor the patient over the weekend (17-18May2025), and the patient received empiric
antibiotics whilst awaiting blood culture results.
The sponsor has met with external pump vendor to arrange removal of the pump from the site and
initiation of manufacturer investigation.
A replacement pump was provided on 27May2025, and Study Nurse, Pharmacist and PI were
retrained by the pump training vendor, on pump procedures prior to restarting patient on Induction
cycle 2.
Further corrective and preventative actions will be assessed once the manufacturer's report is
available.
Actual Impact:
Subject experienced events of low-grade fever (grade 1) and mild distal tremors in hands (grade 1)
for a duration of 1 day. These are well characterized common side effects associated with
blinatumomab treatment (as described in the EU SmPC); subject was hospitalized for monitoring as
a precaution for a duration of 5 days (16-20May2025). After discharge, the subject resumed
treatment with cIV blinatumomab on 02Jun2025 (Induction Cycle 2).

Organisation	City	Country	Type
Centro Hospitalar E Universitario De Coimbra E.P.E.	Coimbra	Portugal	Clinical investigator

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 353 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Type	Title	Version
Clinical study report (for publication)	CSR_Synopsis Interim Analysis Protocol_2023-503640-14_For Publication	1
Clinical study report (for publication)	CSR_Synopsis Interim Analysis Report_2023-503640-14_For Publication	1
Clinical study report (for publication)	CSR_Synopsis Interim Analysis Synopsis_2023-503640-14_For Publication	1
Protocol (for publication)	D1_Protocol_ENG_2023-503640-14_20190360_CSS_For Publication	1
Protocol (for publication)	D1_Protocol_ENG_2023-503640-14_20190360_EEA CSS_For Publication	5
Protocol (for publication)	D1_Protocol_ENG_2023-503640-14_20190360_For Publication	8
Protocol (for publication)	D1_Protocol_ENG_2023-503640-14_20190360_SOC_For Publication	7
Protocol (for publication)	D4_Patient facing documents eCOA ePRO_ENG_2023-503640-14_20190360_For Publication	1
Protocol (for publication)	D4_Patient facing documents Placeholder_ENG_2023-503640-14_20190360_Not For Publication	1
Protocol (for publication)	D4_Patient facing documents Screen Report_CZ_2023-503640-14_20190360_Not For Publication	1
Protocol (for publication)	D4_Patient facing documents Screen Report_EE Russia_2023-503640-14_20190360_Not For Publication	1
Protocol (for publication)	D4_Patient facing documents Screen Report_EE_2023-503640-14_20190360_Not For Publication	1
Protocol (for publication)	D4_Patient facing documents Screen Report_SK_2023-503640-14_20190360_Not For Publication	1
Recruitment arrangements (for publication)	K1 Recruitment arrangements_For publication	1.0
Recruitment arrangements (for publication)	K1_ Recruitment arrangements	1.0
Recruitment arrangements (for publication)	K1_ Recruitment arrangements_For publication	2.0
Recruitment arrangements (for publication)	K1_Recruitment arrangement_Recruitment procedure_ For Publication	2
Recruitment arrangements (for publication)	K1_Recruitment arrangements	1.0
Recruitment arrangements (for publication)	K1_Recruitment arrangements FP	1
Recruitment arrangements (for publication)	K1_Recruitment arrangements Procedure fp	1.0
Recruitment arrangements (for publication)	K1_Recruitment arrangements Recruitment Procedure For Publication	1
Recruitment arrangements (for publication)	K1_Recruitment Arrangements_Austria_20190360_Dummy Document_for publication	1.0
Recruitment arrangements (for publication)	K1_Recruitment arrangements_For Publication	1
Recruitment arrangements (for publication)	K1_Recruitment arrangements_For Publication	1
Recruitment arrangements (for publication)	K1_Recruitment Arrangements_For Publication	1.0
Recruitment arrangements (for publication)	K1_Recruitment arrangements_For publication	1
Recruitment arrangements (for publication)	K1_Recruitment arrangements_For Publication	1
Recruitment arrangements (for publication)	K1_Recruitment arrangements_For Publication	1
Recruitment arrangements (for publication)	K1_Recruitment arrangements_FP	1
Recruitment arrangements (for publication)	K1_Recruitment arrangements_Recruitment and Informed consent procedure_FP	1.0
Recruitment arrangements (for publication)	K1_Recruitment procedure_For Publication	1
Recruitment arrangements (for publication)	K1_Recruitment procedure_For Publication	1.0
Recruitment arrangements (for publication)	K2_ Recruitment material HCP Study Fact Sheet_FP	3.0
Recruitment arrangements (for publication)	K2_Recruitement Arrangements_Referral letter_EN_FP	2.0
Recruitment arrangements (for publication)	K2_Recruitement Arrangements_Referral letter_FR_FP	2
Recruitment arrangements (for publication)	K2_Recruitement Arrangements_Referral letter_NL_FP	2
Recruitment arrangements (for publication)	K2_Recruitment material description_HCP Fact Sheet	4.0
Recruitment arrangements (for publication)	K2_Recruitment material description_HCP Referral Letter	2.0
Recruitment arrangements (for publication)	K2_Recruitment material Dr to Dr Letter_For Publication	1.0
Recruitment arrangements (for publication)	K2_Recruitment material Dr to Dr Referral Letter_FP	2.0
Recruitment arrangements (for publication)	K2_Recruitment material HCP Fact Sheet fp	2.0
Recruitment arrangements (for publication)	K2_Recruitment material HCP Referral letter fp	1.0
Recruitment arrangements (for publication)	K2_Recruitment material HCP study fact sheet FP	4
Recruitment arrangements (for publication)	K2_Recruitment material Patient Journey_GMALL Arm_FP	4
Recruitment arrangements (for publication)	K2_Recruitment material Patient Journey_HyperCVAD Arm_FP	4
Recruitment arrangements (for publication)	K2_Recruitment material Patient Journey_Investigational Arm_FP	4
Recruitment arrangements (for publication)	K2_Recruitment material Referral letter FP	3
Recruitment arrangements (for publication)	K2_Recruitment material Supportive Tool GMALL For Publication	4
Recruitment arrangements (for publication)	K2_Recruitment material Supportive Tool Investigational Arm For Publication	4
Recruitment arrangements (for publication)	K2_Recruitment material_Asseveration Certificate for Albanian documents_For Publication	1
Recruitment arrangements (for publication)	K2_Recruitment material_Dr to Dr referral letter_EN_FP	2
Recruitment arrangements (for publication)	K2_Recruitment material_Dr to Dr referral letter_For Publication	2.0
Recruitment arrangements (for publication)	K2_Recruitment material_Dr to Dr referral letter_FP	1.0
Recruitment arrangements (for publication)	K2_Recruitment material_Dr to Dr referral letter_FP	2
Recruitment arrangements (for publication)	K2_Recruitment Material_dummy document	1
Recruitment arrangements (for publication)	K2_Recruitment material_GMALL arm_For Publication	2.0
Recruitment arrangements (for publication)	K2_Recruitment material_HCP Referral Letter_For Publication	2
Recruitment arrangements (for publication)	K2_Recruitment material_HCP Study Fact Sheet	4.0
Recruitment arrangements (for publication)	K2_Recruitment material_HCP Study Fact Sheet_For Publication	4.0
Recruitment arrangements (for publication)	K2_Recruitment material_HCP Study Fact Sheet_FP	4.0
Recruitment arrangements (for publication)	K2_Recruitment material_HCP Study Fact Sheet_tracked changes	4.0
Recruitment arrangements (for publication)	K2_Recruitment material_HyperCVAD arm_For Publication	2.0
Recruitment arrangements (for publication)	K2_Recruitment material_Investigational arm_For Publication	2.0
Recruitment arrangements (for publication)	K2_Recruitment material_Patient Journey Schema_HyperCVAD_For Publication	4
Recruitment arrangements (for publication)	K2_Recruitment material_Patient Journey Schema_Investigational Arm_For Publication	4
Recruitment arrangements (for publication)	K2_Recruitment material_Patient Journey_GMALL Arm _For Publication	4.0
Recruitment arrangements (for publication)	K2_Recruitment material_Patient Journey_Hyper-CVAD Arm _For Publication	4.0
Recruitment arrangements (for publication)	K2_Recruitment material_Patient Journey_Investigational Arm_For Publication	4.0
Recruitment arrangements (for publication)	K2_Recruitment material_Physician Facing Material_HCP Referral Letter	2.0
Recruitment arrangements (for publication)	K2_Recruitment material_Physician Facing Material_HCP Referral Letter_FP	2.0
Recruitment arrangements (for publication)	K2_Recruitment material_Subject Facing Material GMALL_For Publication	4
Recruitment arrangements (for publication)	K2_Recruitment material_Subject Facing Material HyperCVAD_For Publication	4
Recruitment arrangements (for publication)	K2_Recruitment material_Subject Facing Material Investigational Arm_For Publication	4
Recruitment arrangements (for publication)	K2_Recruitment material_Subject Facing Material_patient journeys_EXP arm	4.0
Recruitment arrangements (for publication)	K2_Recruitment material_Subject Facing Material_patient journeys_EXP_FP	4.0
Recruitment arrangements (for publication)	K2_Recruitment material_Subject Facing Material_patient journeys_GMALL arm	4.0
Recruitment arrangements (for publication)	K2_Recruitment material_Subject Facing Material_patient journeys_GMALL arm_FP	4.0
Recruitment arrangements (for publication)	K2_Recruitment material_Subject Facing Supportive Tool_Investigational Arm_FI_For Publication	4
Recruitment arrangements (for publication)	K2_Recruitment material_Subject Facing Supportive Tool_Investigational Arm_SE_For Publication	4
Recruitment arrangements (for publication)	K2_Recruitment material_Subject Facing Supportive Tool_SoC Arm_GMALL_FI_For Publication	4
Recruitment arrangements (for publication)	K2_Recruitment material_Subject Facing Supportive Tool_SoC Arm_GMALL_SE_For Publication	4
Recruitment arrangements (for publication)	K2_Recruitment material_Subject Facing Supportive Tool_SoC Arm_HyperCVAD_FI_For Publication	4
Recruitment arrangements (for publication)	K2_Recruitment material_Subject Facing Supportive Tool_SoC Arm_HyperCVAD_SE_For Publication	4
Recruitment arrangements (for publication)	K2_Recruitment material_Supportive tool for consent process GMALL_For Publication	4
Recruitment arrangements (for publication)	K2_Recruitment material_Supportive tool for consent process HyperCVAD_For Publication	4
Recruitment arrangements (for publication)	K2_Recruitment material_Supportive tool for consent process Investigational Arm_Albanian_FP	4.0
Recruitment arrangements (for publication)	K2_Recruitment material_Supportive tool for consent process Investigational Arm_For Publication	4
Subject information and informed consent form (for publication)	L1 SIS and ICF Main ICF GMALL_For Publication	5.1
Subject information and informed consent form (for publication)	L1_ SIS and ICF Albanian Future Research GMALL_For Publication	5.0
Subject information and informed consent form (for publication)	L1_ SIS and ICF Albanian Genetic Research GMALL_For Publication	5.0
Subject information and informed consent form (for publication)	L1_ SIS and ICF Albanian Main GMALL_For Publication	6.0
Subject information and informed consent form (for publication)	L1_ SIS and ICF Future Research GMALL For Publication	8.0
Subject information and informed consent form (for publication)	L1_ SIS and ICF Future research HyperCVAD For Publication	7.0
Subject information and informed consent form (for publication)	L1_ SIS and ICF Genetic GMALL_For Publication	4
Subject information and informed consent form (for publication)	L1_ SIS and ICF Genetic HyperCVAD_For Publication	4
Subject information and informed consent form (for publication)	L1_ SIS and ICF Genetic Research GMALL For Publication	8.0
Subject information and informed consent form (for publication)	L1_ SIS and ICF Genetic Research HyperCVAD For Publication	7.0
Subject information and informed consent form (for publication)	L1_ SIS and ICF home healthcare service GMALL For Publication	7.0
Subject information and informed consent form (for publication)	L1_ SIS and ICF home healthcare service HyperCVAD For Publication	7.0
Subject information and informed consent form (for publication)	L1_ SIS and ICF Main GMALL For Publication	9.0
Subject information and informed consent form (for publication)	L1_ SIS and ICF Main GMALL_For Publication	6.0
Subject information and informed consent form (for publication)	L1_ SIS and ICF Main HyperCVAD For Publication	7.0
Subject information and informed consent form (for publication)	L1_ SIS and ICF Main HyperCVAD_For Publication	6.0
Subject information and informed consent form (for publication)	L1_ SIS and ICF Pregnancy Man_For Publication	1
Subject information and informed consent form (for publication)	L1_ SIS and ICF Pregnancy Woman_For Publication	1
Subject information and informed consent form (for publication)	L1_ SIS and ICF shipment of IP and home administration GMALL For Publication	7.0
Subject information and informed consent form (for publication)	L1_ SIS and ICF shipment of IP and home administration HyperCVAD For Publication	7.0
Subject information and informed consent form (for publication)	L1_ SIS and ICF Withdrawal_For Publication	1.1
Subject information and informed consent form (for publication)	L1_ SIS and ICF_Informed Consent Procedure	2.0
Subject information and informed consent form (for publication)	L1_ICF_HHC Addendum_GMALL_EN_For Publication	3.0
Subject information and informed consent form (for publication)	L1_ICF_HHC addendum_GMALL_FR_For Publication	3.0
Subject information and informed consent form (for publication)	L1_ICF_HHC addendum_GMALL_NL_For Publication	3.0
Subject information and informed consent form (for publication)	L1_ICF_HHC addendum_HCVAD_EN_For Publication	3.0
Subject information and informed consent form (for publication)	L1_ICF_HHC addendum_HCVAD_FR_For Publication	3.0
Subject information and informed consent form (for publication)	L1_ICF_HHC addendum_HCVAD_NL_For publication	3.0
Subject information and informed consent form (for publication)	L1_Informed Consent Procedure_For Publication	1.0
Subject information and informed consent form (for publication)	L1_Main_ICF_GMALL_EN_For Publication	4.1
Subject information and informed consent form (for publication)	L1_Main_ICF_GMALL_FR_For Publication	4.1
Subject information and informed consent form (for publication)	L1_Main_ICF_GMALL_NL_For Publication	4.1
Subject information and informed consent form (for publication)	L1_Main_ICF_HCVAD_EN_For Publication	4.1
Subject information and informed consent form (for publication)	L1_Main_ICF_HCVAD_FR_For Publication	4.1
Subject information and informed consent form (for publication)	L1_Main_ICF_HCVAD_NL_For Publication	4.1
Subject information and informed consent form (for publication)	L1_SIS and ICF adults GMALL_English_For Publication	4.0
Subject information and informed consent form (for publication)	L1_SIS and ICF adults GMALL_Translation Bulgarian_For Publication	4.0
Subject information and informed consent form (for publication)	L1_SIS and ICF adults hyperCVAD_English_For Publication	5.0
Subject information and informed consent form (for publication)	L1_SIS and ICF adults hyperCVAD_Translation Bulgarian_For Publication	5.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Albanian Future Research GMALL_for publication	7.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Albanian Genetic Research GMALL_for publication	7.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Albanian Main GMALL_for publication	8.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Asseveration Certificate for Albanian documents_For Publication	2.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Female Info release fp	2.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Female Participant Info fp	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Future GMALL fp	1.1
Subject information and informed consent form (for publication)	L1_SIS and ICF Future HyperCVAD fp	1.1
Subject information and informed consent form (for publication)	L1_SIS and ICF Future Research GMALL EE_EE_FP	29APR2025
Subject information and informed consent form (for publication)	L1_SIS and ICF Future Research GMALL EE_RU_FP	29APR2025
Subject information and informed consent form (for publication)	L1_SIS and ICF Future Research GMALL_For Publication	4.1
Subject information and informed consent form (for publication)	L1_SIS and ICF Future Research HyperCVAD EE_EE_FP	29APR2025
Subject information and informed consent form (for publication)	L1_SIS and ICF Future Research HyperCVAD EE_RU_FP	29APR2025
Subject information and informed consent form (for publication)	L1_SIS and ICF Future Research HyperCVAD_For Publication	4.1
Subject information and informed consent form (for publication)	L1_SIS and ICF Future Research Informed Consent_GMALL_FP	7.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Future Research Informed Consent_HCVAD_FP	7.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Future Research Legal Representative_FP	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Genetic fp	2.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Genetic HyperCVAD fp	2.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Genetic Research For Publication	8
Subject information and informed consent form (for publication)	L1_SIS and ICF Genetic Research GMALL EE_EE_FP	29APR2025
Subject information and informed consent form (for publication)	L1_SIS and ICF Genetic Research GMALL EE_RU_FP	29APR2025
Subject information and informed consent form (for publication)	L1_SIS and ICF Genetic Research HyperCVAD EE_EE_FP	29APR2025
Subject information and informed consent form (for publication)	L1_SIS and ICF Genetic Research HyperCVAD EE_RU_FP	29APR2025
Subject information and informed consent form (for publication)	L1_SIS and ICF Genetic Research Informed Consent_GMALL_FP	7.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Genetic Research Informed Consent_HCVAD_FP	7.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Genetic Research Legal Representative_FP	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF HHC GMALL fp	1.1
Subject information and informed consent form (for publication)	L1_SIS and ICF HHC HyperCVAD fp	1.1
Subject information and informed consent form (for publication)	L1_SIS and ICF HHC Informed Consent_GMALL_FP	7.0
Subject information and informed consent form (for publication)	L1_SIS and ICF HHC Informed Consent_HCVAD_FP	7.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Home Healthcare GMALL_For Publication	1
Subject information and informed consent form (for publication)	L1_SIS and ICF Home Healthcare HyperCVAD_For Publication	1
Subject information and informed consent form (for publication)	L1_SIS and ICF Home Healthcare Legal Representative_FP	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Home Healthcare Visits_FP	2.0
Subject information and informed consent form (for publication)	L1_SIS and ICF IP SHIPMENT GMALL fp	1.1
Subject information and informed consent form (for publication)	L1_SIS and ICF IP SHIPMENT HyperCVAD fp	1.1
Subject information and informed consent form (for publication)	L1_SIS and ICF IP-TO-HOME Informed Consent_GMALL_FP	7.0
Subject information and informed consent form (for publication)	L1_SIS and ICF IP-TO-HOME Informed Consent_HCVAD_FP	7.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Main For Publication	11
Subject information and informed consent form (for publication)	L1_SIS and ICF Main GMALL Estonian_FP	03NOV2025
Subject information and informed consent form (for publication)	L1_SIS and ICF Main GMALL fp	5.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Main GMALL Legal Representative_Redacted For Publication	2.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Main GMALL_For Publication	6.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Main GMALL_Russian_FP	03NOV2025
Subject information and informed consent form (for publication)	L1_SIS and ICF Main HyperCVAD Estonian_FP	03NOV2025
Subject information and informed consent form (for publication)	L1_SIS and ICF Main HyperCVAD fp	5.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Main HyperCVAD Legal Representative_Redacted For Publication	2.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Main HyperCVAD Russian_FP	03NOV2025
Subject information and informed consent form (for publication)	L1_SIS and ICF Main HyperCVAD_For Publication	6.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Main Informed Consent_GMALL_FP	7.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Main Informed Consent_HCVAD_FP	7.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Main Patient information sheet_FP	1
Subject information and informed consent form (for publication)	L1_SIS and ICF Main Patient information sheet_Translation_FP	1
Subject information and informed consent form (for publication)	L1_SIS and ICF Main Study _HyperCVAD _FP	6.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Main Study_GMALL_FP	6.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Main_GMALL_Eng_For Publication	6
Subject information and informed consent form (for publication)	L1_SIS and ICF Main_GMALL_Translation_For Publication	6
Subject information and informed consent form (for publication)	L1_SIS and ICF Main_hyperCVAD_Eng_For publication	6
Subject information and informed consent form (for publication)	L1_SIS and ICF Main_hyperCVAD_Translation_For publication	6
Subject information and informed consent form (for publication)	L1_SIS and ICF Site to Patient Shipment of IP Legal Representative_FP	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Site to Patient Shipment of IP_FP	2.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Withdrawal GMALL Legal Representative_FP	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF Withdrawal HyperCVAD Legal Representative_FP	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF_Asseveration Certificate for Albanian documents_For Publication	1
Subject information and informed consent form (for publication)	L1_SIS and ICF_Future research	8.0
Subject information and informed consent form (for publication)	L1_SIS and ICF_Future Research ICF Study _FP	2.0
Subject information and informed consent form (for publication)	L1_SIS and ICF_Future Research_for publication	8.2
Subject information and informed consent form (for publication)	L1_SIS and ICF_Future research_FP	8.1
Subject information and informed consent form (for publication)	L1_SIS and ICF_GDPR_FP	1.1
Subject information and informed consent form (for publication)	L1_SIS and ICF_Genetic GMALL ICF_For Publication	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF_Genetic Hyper-CVAD ICF_For Publication	4.0
Subject information and informed consent form (for publication)	L1_SIS and ICF_Genetic research	8.0
Subject information and informed consent form (for publication)	L1_SIS and ICF_Genetic Research ICF Study _FP	2.0
Subject information and informed consent form (for publication)	L1_SIS and ICF_Genetic Research_for publication	8.2
Subject information and informed consent form (for publication)	L1_SIS and ICF_Genetic Research_For Publication	22OCT2024
Subject information and informed consent form (for publication)	L1_SIS and ICF_Genetic Research_sub-study_FI_For Publication	8
Subject information and informed consent form (for publication)	L1_SIS and ICF_Genetic testing_FP	8.1
Subject information and informed consent form (for publication)	L1_SIS and ICF_Home Healthcare GMALL ICF_For Publication	0
Subject information and informed consent form (for publication)	L1_SIS and ICF_Home Healthcare Hyper-CVAD ICF_For Publication	3.0
Subject information and informed consent form (for publication)	L1_SIS and ICF_Informed Consent Procedure_For Publication	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF_IP ship to Home GMALL ICF_For Publication	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF_IP ship to Home Hyper-CVAD ICF_For Publication	3.0
Subject information and informed consent form (for publication)	L1_SIS and ICF_Leaflet_GMALL_FI_For Publication	11
Subject information and informed consent form (for publication)	L1_SIS and ICF_Leaflet_HyperCVAD_FI_For Publication	11
Subject information and informed consent form (for publication)	L1_SIS and ICF_Main GMALL ICF_Redacted version_For Publication	4.0
Subject information and informed consent form (for publication)	L1_SIS and ICF_Main GMALL_for publication	8.1
Subject information and informed consent form (for publication)	L1_SIS and ICF_Main Hyper-CVAD ICF_Redacted Version_For Publication	7.0
Subject information and informed consent form (for publication)	L1_SIS and ICF_Main hyperCVAD_for publication	8.1
Subject information and informed consent form (for publication)	L1_SIS and ICF_Main_Enrolled participants_For Publication	11.0
Subject information and informed consent form (for publication)	L1_SIS and ICF_Main_For Publication	27OCT2025
Subject information and informed consent form (for publication)	L1_SIS and ICF_Main_FP	11.0
Subject information and informed consent form (for publication)	L1_SIS and ICF_Main_GMALL_FI_For Publication	11
Subject information and informed consent form (for publication)	L1_SIS and ICF_Main_HyperCVAD_FI_For Publication	11
Subject information and informed consent form (for publication)	L1_SIS and ICF_Main_New Participants_For publication	11.0
Subject information and informed consent form (for publication)	L1_SIS and ICF_Pregnancy follow up program ICF_For Publication	1
Subject information and informed consent form (for publication)	L1_SIS and ICF_Pregnancy Partner follow up program ICF_For Publication	1
Subject information and informed consent form (for publication)	L1_SIS and ICF_Withdraw ICF _GMALL_FP	3.0
Subject information and informed consent form (for publication)	L1_SIS and ICF_Withdraw ICF _HyperCVAD _FP	3.0
Subject information and informed consent form (for publication)	L1_SIS and ICF_Withdrawal ICF_For Publication	1
Subject information and informed consent form (for publication)	L2_ Informed Consent Procedure_For Publication	1.0
Subject information and informed consent form (for publication)	L2_ Other subject information material_Informed consent procedure_For Publication	1.0
Subject information and informed consent form (for publication)	L2_ Other subject information material_Patient Journey on study_Subject facing_GMALL regimen	4.0
Subject information and informed consent form (for publication)	L2_ Other subject information material_Patient Journey on study_Subject facing_HyperCVAD regimen	4.0
Subject information and informed consent form (for publication)	L2_ Other subject information material_Patient Journey on study_Subject facing_Investigational Arm	4.0
Subject information and informed consent form (for publication)	L2_ Other subject information__Patient Diary _HyperCVAD arm_FP	4.0
Subject information and informed consent form (for publication)	L2_ Other subject information__Patient Diary_Investigational arm_FP	4.0
Subject information and informed consent form (for publication)	L2_ Other subject information_Patient Diary _GMALL arm_FP	4.0
Subject information and informed consent form (for publication)	L2_ Other subject information_Patient Diary for Dexamethasone_GMALL arm_FP	4.0
Subject information and informed consent form (for publication)	L2_Informed Consent Procedure For Publication	1
Subject information and informed consent form (for publication)	L2_Informed Consent Procedure fp	1.0
Subject information and informed consent form (for publication)	L2_Informed Consent Procedure_For Publication	1
Subject information and informed consent form (for publication)	L2_Informed consent procedure_For Publication	2
Subject information and informed consent form (for publication)	L2_Informed consent procedure_For Publication	1
Subject information and informed consent form (for publication)	L2_List of patient material documents fp	1.0
Subject information and informed consent form (for publication)	L2_Other subject info material_Patient Journey GMALL_FP	4
Subject information and informed consent form (for publication)	L2_Other subject info material_Patient Journey Inv Arm_FP	4
Subject information and informed consent form (for publication)	L2_Other subject information material GP Letter Albanian Investigational Arm For Publication	6.0
Subject information and informed consent form (for publication)	L2_Other subject information material GP Letter Investigational Arm For Publication	7.0
Subject information and informed consent form (for publication)	L2_Other subject information material GP Letter SOC GMALL Arm For Publication	7.0
Subject information and informed consent form (for publication)	L2_Other subject information material GP Letter SOC HyperCVAD Arm For Publication	7.0
Subject information and informed consent form (for publication)	L2_Other subject information material GP Letter_EXP arm blinatumomab	7.0
Subject information and informed consent form (for publication)	L2_Other subject information material GP Letter_SOC arm GMALL	7.0
Subject information and informed consent form (for publication)	L2_Other subject information material GP Letter_SOC arm HyperCVAD	7.0
Subject information and informed consent form (for publication)	L2_Other subject information material Informed consent procedure _For publication	1.0
Subject information and informed consent form (for publication)	L2_Other subject information material Informed consent procedure FP	1
Subject information and informed consent form (for publication)	L2_Other subject information material Informed Consent Procedure_FP	1
Subject information and informed consent form (for publication)	L2_Other subject information material Patient Journey GMALL_EE	4
Subject information and informed consent form (for publication)	L2_Other subject information material Patient Journey GMALL_RU	4
Subject information and informed consent form (for publication)	L2_Other subject information material Patient Journey HyperCVAD_EE	4
Subject information and informed consent form (for publication)	L2_Other subject information material Patient Journey HyperCVAD_RU	4
Subject information and informed consent form (for publication)	L2_Other subject information material Patient Journey Investigational Arm_EE	4
Subject information and informed consent form (for publication)	L2_Other subject information material Patient Journey Investigational Arm_RU	4
Subject information and informed consent form (for publication)	L2_Other subject information material_Albanian GP letter Investigational Arm_For Publication	5.0
Subject information and informed consent form (for publication)	L2_Other subject information material_CF for release of Pregnancy Lactation and Infant health_FP	1.0
Subject information and informed consent form (for publication)	L2_Other subject information material_GDPR	6.1
Subject information and informed consent form (for publication)	L2_Other subject information material_Informed consent procedure_For publication	1
Subject information and informed consent form (for publication)	L2_Other subject information material_Informed consent procedure_FP	1
Subject information and informed consent form (for publication)	L2_Other subject Information Material_Journey Schema_GMALL_EN_FP	4.0
Subject information and informed consent form (for publication)	L2_Other subject Information Material_Journey Schema_GMALL_FR_FP	4.0
Subject information and informed consent form (for publication)	L2_Other subject Information Material_Journey Schema_GMALL_NL_FP	4.0
Subject information and informed consent form (for publication)	L2_Other subject Information Material_Journey Schema_HCVAD_EN_FP	4.0
Subject information and informed consent form (for publication)	L2_Other subject Information Material_Journey Schema_HCVAD_FR_FP	4.0
Subject information and informed consent form (for publication)	L2_Other subject Information Material_Journey Schema_HCVAD_NL_FP	4.0
Subject information and informed consent form (for publication)	L2_Other subject Information Material_Journey Schema_Inv arm_EN_FP	4.0
Subject information and informed consent form (for publication)	L2_Other subject Information Material_Journey Schema_Inv arm_FR_FP	4.0
Subject information and informed consent form (for publication)	L2_Other subject Information Material_Journey Schema_Inv arm_NL_FP	4.0
Subject information and informed consent form (for publication)	L2_Other subject information material_Patient card_FP	2
Subject information and informed consent form (for publication)	L2_Other subject information material_Patient Diary_ GMALL Investigational Arm_For Publication	7.0
Subject information and informed consent form (for publication)	L2_Other subject information material_Patient Diary_GMALL Arm_For Publication	7.0
Subject information and informed consent form (for publication)	L2_Other subject information material_Patient Diary_HyperCVAD Arm_For Publication	7.0
Subject information and informed consent form (for publication)	L2_Other subject information material_Patient Diary_HyperCVAD Investigational Arm_For Publication	7.0
Subject information and informed consent form (for publication)	L2_Other subject information material_Subject facing_GMALL_EN_FP	4
Subject information and informed consent form (for publication)	L2_Other subject information material_Subject facing_GMALL_FP	4
Subject information and informed consent form (for publication)	L2_Other subject information material_Subject facing_hyperCVAD_EN_FP	4
Subject information and informed consent form (for publication)	L2_Other subject information material_Subject facing_hyperCVAD_FP	4
Subject information and informed consent form (for publication)	L2_Other subject information material_Subject facing_Inv arm_EN_FP	4
Subject information and informed consent form (for publication)	L2_Other subject information material_Subject facing_Inv arm_FP	4
Subject information and informed consent form (for publication)	L2_Other subject information material_Supportive tool Experimental Arm_For Publication	4.0
Subject information and informed consent form (for publication)	L2_Other subject information material_Supportive tool GMALL_For Publication	4.0
Subject information and informed consent form (for publication)	L2_Other subject information material_Supportive tool hyperCVAD_For Publication	3.0
Subject information and informed consent form (for publication)	L2_Other Subject information_Participant rights in a trial_For Publication	1
Subject information and informed consent form (for publication)	L2_Patient Card fp	1.0
Subject information and informed consent form (for publication)	L2_Patient Journey GMALL regimen fp	4.0
Subject information and informed consent form (for publication)	L2_Patient Journey HyperCVAD regimen fp	4.0
Subject information and informed consent form (for publication)	L2_Patient Journey Investigational arm fp	4.0
Subject information and informed consent form (for publication)	L2_Reimbursement agreement general fp	3.0
Subject information and informed consent form (for publication)	L2_Reimbursement agreement individual fp	3.0
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_Asparaginase IV_For Publication	1
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_Asparaginase IV_For Publication	2
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_Asparaginase IV_TC_For Publication	1
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_blincyto_For Publication	1
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_blincyto_For Publication	1
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_Cyclophosphamide IV_For Publication	1
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_Cyclophosphamide IV_For Publication	1
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_cytarabine IV_For Publication	1
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_cytarabine IV_For Publication	1
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_Dexamethasone IV_For Publication	1
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_Dexamethasone IV_For Publication	1
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_dexamethasone PO_For Publication	1
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_dexamethasone PO_For Publication	1
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_doxorubicin IV_For Publication	1
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_idarubicin IV _For Publication	2
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_mercaptopurine PO_For Publication	2
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_mercaptopurine PO_For Publication	2
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_mercaptopurine PO_TC_For Publication	1
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_mercaptopurine PO_TC_For Publication	1
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_Methotrexate IV_For Publication	2
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_Methotrexate IV_For Publication	2
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_methotrexate PO_For Publication	2
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_methotrexate PO_For Publication	2
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_PEG-asparaginase IV_For Publication	2
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_PEG-asparaginase IV_TC_For Publication	1
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_prednisolone PO_For Publication	1
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_prednisone PO_For Publication	1
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_rituximab IV_For Publication	2
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_rituximab IV_For Publication	2
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_rituximab IV_TC_For Publication	1
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_rituximab IV_TC_For Publication	1
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_vincristine IV_For Publication	2
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC_vincristine IV_For Publication	2
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_AT DE_2023-503640-14_20190360_PLPS_For Publication	1
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_BE DE_2023-503640-14_20190360_PLPS_For Publication	3
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_BE FR_2023-503640-14_20190360_PLPS_For Publication	3
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_BE NL_2023-503640-14_20190360_PLPS_For Publication	3
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_BG_2023-503640-14_20190360_PLPS_For Publication	3
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_CZ_2023-503640-14_20190360_PLPS_For Publication	3
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_DE_2023-503640-14_20190360_For Publication	1
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_DK_2023-503640-14_20190360_PLPS_For Publication	1
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_ENG_2023-503640-14_20190360_PLPS_For Publication	3
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_ES_2023-503640-14_20190360_PLPS_For Publication	3
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_FI_2023-503640-14_20190360_PLPS_For Publication	1
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_FR_2023-503640-14_20190360_For Publication	5
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_FR_2023-503640-14_20190360_PLPS_For Publication	3
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_GR_2023-503640-14_20190360_For Publication	1
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_GR_2023-503640-14_20190360_PLPS_For Publication	3
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_HU_2023-503640-14_20190360_PLPS_For Publication	3
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_IT_2023-503640-14_20190360_For Publication	3
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_IT_2023-503640-14_20190360_PLPS_For Publication	3
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_NL_2023-503640-14_20190360_PLPS_For Publication	3
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_PT_2023-503640-14_20190360_For Publication	1
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_PT_2023-503640-14_20190360_PLPS_For Publication	3
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_RO_2023-503640-14_20190360_For Publication	1
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_RO_2023-503640-14_20190360_PLPS_For Publication	3
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_SE_2023-503640-14_20190360_For Publication	1
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_SE_2023-503640-14_20190360_PLPS_For Publication	3
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_SK_2023-503640-14_20190360_PLPS_For Publication	3

Application history

11 submissions — initial application plus substantial / non-substantial modifications

#	Type	Code	Submitted	Reference MS	Conclusion	Decision date
1	INITIAL	IN	2024-02-22	Austria	Acceptable 2024-04-18	2024-04-18
2	NON SUBSTANTIAL MODIFICATION	NSM-1	2024-08-08	Austria	Acceptable 2024-04-18	2024-08-08
3	SUBSTANTIAL MODIFICATION	SM-1	2024-10-29	Austria	Acceptable with conditions 2025-02-17	2025-02-18
4	SUBSEQUENT ADDITION OF MSC	APP-4	2025-03-03			2025-05-29
5	SUBSEQUENT ADDITION OF MSC	APP-5	2025-03-03		Acceptable with conditions 2025-02-17	2025-06-02
6	SUBSEQUENT ADDITION OF MSC	APP-6	2025-03-03			2025-05-23
7	SUBSTANTIAL MODIFICATION	SM-2	2025-03-12		Acceptable with conditions	2025-04-25
8	SUBSTANTIAL MODIFICATION	SM-3	2025-03-13		Acceptable with conditions	2025-04-28
9	SUBSTANTIAL MODIFICATION	SM-4	2025-07-02		Acceptable 2025-10-06	2025-10-07
10	NON SUBSTANTIAL MODIFICATION	NSM-2	2025-10-23		Acceptable 2025-10-06	2025-10-23
11	SUBSTANTIAL MODIFICATION	SM-6	2025-11-13		Acceptable 2026-02-06	2026-02-09

A Randomized Study Comparing Blinatumomab Alternating With Low-intensity Chemotherapy Versus Standard of Care Chemotherapy for Older Adults With Newly Diagnosed Philadelphia-negative B-cell Precursor Acute Lymphoblastic Leukemia with Safety Run-in (Golden Gate Study)

Overview

Key facts

External identifiers

Trial design

Main objective

Secondary objectives 16

Conditions and MedDRA coding

Study design 2 periods

Regulatory references

Eligibility criteria

Inclusion criteria 5

Exclusion criteria 9

Endpoints

Primary endpoints 3

Secondary endpoints 30

Investigational products

Test 10

Comparator 17

Sponsors and contacts

Amgen Inc.

Scientific contact point

Public contact point

Third parties 14

Locations

By country

Investigational sites

Country notifications

Oversight and notifications

Serious breaches 1 · Art. 52 CTR

Results and documents

Documents 353 files

Application history

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