A phase 1/2 study of subcutaneous blinatumomab administration in children with R/R and MRD+ B-ALL

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amgen Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-02-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Amgen Inc.

External identifiers

EU CT number

2025-521671-31-00

WHO UTN

U1111-1320-7216

ClinicalTrials.gov

NCT07134088

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy

Phase 1b: To evaluate the safety and tolerability of SC blinatumomab in children below 12 years of age
Phase 2 Cohort Ph2-R & M: To evaluate the efficacy of SC blinatumomab

Secondary objectives 13

1. Phase 1b: To evaluate the efficacy of SC blinatumomab
2. Phase 1b: To evaluate the effect of SC blinatumomab on the rate of MRD negative response
3. Phase 1b: To evaluate the effect of SC blinatumomab on the duration of response (DOR)
4. Phase 1b: To evaluate the pharmacokinetics (PK) of SC blinatumomab
5. Phase 1b: To evaluate the immunogenicity of SC blinatumomab
6. Phase 2 Cohort Ph2-R Key Secondary: To evaluate the effect of SC blinatumomab on the rate of MRD negative response
7. Phase 2 Cohort Ph2-R & Ph2-M Key Secondary:To evaluate the effect of SC blinatumomab on the DOR
8. Phase 2 Cohort Ph2 -R & M: Evaluate the efficacy of SC blinatumomab
9. Phase 2 Cohort Ph2-R & M: To evaluate the effect of SC blinatumomab on overall survival (OS)
10. Phase 2 Cohort Ph2- R & M: To evaluate the safety of SC blinatumomab
11. Phase 2 Cohort Ph2 - R & M: To evaluate PK of SC blinatumomab
12. Phase 2 Cohort Ph2 - R & M: To evaluate the immunogenicity of SC blinatumomab
13. Phase 2 Cohort Ph2-M Key Secondary: To evaluate the efficacy of SC blinatumomab

Conditions and MedDRA coding

Relapsed/Refractory (R/R) and Minimal Residual Disease Positive (MRD+) B-Cell Precursor Acute Lymphoblastic Leukemia

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-000574-PIP03-23

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.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Participant’s legally authorized representative has provided informed consent when the participant is legally too young to provide informed consent, and the participant has provided written assent based on local regulations and/or guidelines before any study-specific activities/procedures being initiated.
2. Age 28 days to < 12 years at the time of consent
3. Lansky Performance Status (LPS) of ≥ 50%
4. Prior CD19-directed therapy such as blinatumomab or CD19 chimeric antigen receptor T cells (CAR-T) cells will be allowed (with demonstrated continued CD19+ expression) if treatment ended >4 weeks prior to start of protocol therapy and no prior central nervous system (CNS) complications (see CNS exclusion criteria below).
5. Any Philadelphia chromosome-positive (Ph+) participant intolerant or refractory to prior tyrosine kinase inhibitors (TKIs) are eligible.
6. For Phase 1b and Phase 2 cohort in participants with R/R B-ALL (Ph2-R): Participants with B-ALL relapsed after or refractory to any line of treatment including allogeneic HSCT  Refractory disease is defined as the failure to achieve CR.  Relapsed disease is defined as isolated hematological relapse or combined hematological and extramedullary (EM) relapse after achieving a CR. Greater than or equal to 5% blasts in the BM is considered as relapse in the BM.
7. For Phase 2 cohort in participants with MRD+ B-ALL (Ph2-M): Participants with MRD+ B-ALL must have between ≥ 0.1% and < 5% blasts in the BM. With a peripheral blood count as defined below: ANC (neutrophils) ≥ 500/μL; Platelets ≥ 50,000/μL (transfusion permitted)
8. For Phase 2 cohort in participants with MRD+ B-ALL (Ph2-M):Submission of an archival bone marrow specimen from primary diagnosis or relapse for clone-specific calibration of MRD. See section 8.2.9 and the lab manual for minimum sample requirements. For patients in the US and Canada that have a prior Adaptive clonoSEQ result from bone marrow testing that can be made available for use in this study for clone specific calibration, this may be acceptable in lieu of the archival bone marrow specimen with approval by the Medical Monitor. The participant must also provide consent to the use of the prior clonoSEQ result.

Exclusion criteria 17

1. Disease Related: Active ALL in the CNS. If CSF leukemia is present, participants must receive intrathecal therapy and have documented negative CSF prior to enrolling.
2. Other Medical Conditions: History of other malignancy within the past 3 years, with the following exception: 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.
3. Other Medical Conditions: History or presence of clinically relevant CNS pathology or event such as epilepsy, childhood seizure, paresis, aphasia, stroke, severe brain injuries, cerebellar disease, organic brain syndrome, psychosis, or severe (≥ grade 3) CNS events including ICANS from prior CAR-T or other T-cell engager therapies.
4. Other Medical Conditions: Isolated EMdisease
5. Other Medical Conditions: Current autoimmune disease or history of autoimmune disease with potential CNS involvement.
6. Other Medical Conditions: Patients with Down Syndrome are not eligible for this study
7. Prior/Concomitant Therapy: Known hypersensitivity to blinatumomab or to any component of the product formulation. Sensitivity to any of the products administered during dosing.
8. Prior/Concomitant Therapy: Active acute or chronic graft versus host disease requiring systemic treatment with immunosuppressive medication.
9. Prior/Concomitant Therapy: Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus or hepatitis C virus.
10. Prior/Concomitant Therapy: Symptoms and/or clinical signs and/or radiological and/or sonographic signs that indicate an acute or uncontrolled chronic infection, any other concurrent disease or medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol
11. Prior/Concomitant Therapy: Allogeneic HSCT within 12 weeks before the start of blinatumomab
12. Prior/Concomitant Therapy: Cancer chemotherapy within 2 weeks before the start of protocol specified therapy, with the exception of intrathecal chemotherapy and/or low dose maintenance therapy (for example vinca alkaloids, mercaptopurine, methotrexate, or hydroxyurea). Any low dose chemotherapy as stated above must be discontinued before starting pre-phase chemotherapy and/or dexamethasone.
13. Prior/Concomitant Therapy: Immunotherapy (eg, rituximab, alemtuzumab) within 4 weeks before start of protocol specified therapy
14. Prior/Concurrent Clinical Study Experience: Currently receiving treatment in another investigational device or drug study, or less than 30 days or 5 half-lives since ending treatment in another investigational device or drug study(ies). This does not apply to other investigational procedures or participation in observational research studies.
15. Diagnostic Assessments: Abnormal screening laboratory values as defined below: Direct bilirubin > 3.0 mg/dL prior to start of treatment; Estimated Glomerular Filtration Rate (eGFR) < 30 mL/min. per 1.73 m2 per the Revised Schwartz equation for children 2 to < 12 years. For children < 2 years of age, at least 50% of age and gender appropriate normal
16. Other Exclusions: Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, Clinical Outcome Assessments) to the best of the Participant, Participant’s legal guardian’s, and investigator’s knowledge. Completion of patient reported outcomes questionnaires is not required and will not be prohibitive to enrollment in case patient has intellectual disability or cognitive impairment or in case instrument is unavailable in subject’s language.
17. History or evidence of any other clinically significant disorder, condition, or disease (except for those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to participant safety, or interfere with the study evaluation, procedures or completion. Completion of patient reported outcomes questionnaires is not required and will not be prohibitive to enrollment in case patient has intellectual disability or cognitive impairment or in case instrument is unavailable in subject’s language.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Phase 1b: Dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAE), serious TEAE, treatment related TEAE, and adverse events of interest (EOI)
2. Phase 2 R/R B-ALL (Cohort Ph2-R): CR/CRh within the first 2 cycles
3. Phase 2 MRD+ B-ALL (Cohort Ph2-M): CR with MRD negative response (MRD <10-4 [0.01%]) within the first 2 cycles

Secondary endpoints 22

1. Phase 1b: Complete remission/complete remission with partial hematological recovery (CR/CRh) within the first 2 cycles
2. Phase 1b: CR within the first 2 cycles
3. Phase 1b: CR/CRh/CRi/Blast free hypoplastic or aplastic BM within the first 2 cycles
4. Phase 1b: MRD negative response (MRD level < 10-4 [0.01%]) within the first 2 cycles
5. Phase 1b: DOR is defined as the time from the first response of CR/CRh within the first 2 cycles until hematological relapse (Including EM relapse) per investigator’s assessment or death due to any cause, whichever occurs first
6. Phase 1b: PK parameters following SC blinatumomab administration including, but not limited to, maximum concentration (Cmax), time to maximum concentration (Tmax), and area under the concentration time curve (AUC)
7. Phase 1b: Incidence of anti-blinatumomab antibody formation
8. Phase 2 (Cohort Ph2-R) Key Secondary: CR/CRh with MRD negative response (MRD < 10-4 [0.01%]) within the first 2 cycles
9. Phase 2 (Cohort Ph2-R) Key Secondary: DOR is defined as the time from the first response of CR/CRh within the first 2 cycles until hematological relapse (Including EM relapse) per investigator’s assessment or death due to any cause, whichever occurs first
10. Phase 2 (Cohort Ph2-R): CR within the first 2 cycles
11. Phase 2 (Cohort Ph2-R): CR/CRh/CRi/Blast free hypoplastic or aplastic BM within the first 2 cycles
12. Phase 2 (Cohort Ph2-R): OS is defined as the time from the first dose until death due to any cause
13. Phase 2 (Cohort Ph2-R): Incidence of TEAE, serious TEAE, Treatment related TEAE, and EOI
14. Phase 2 (Cohort Ph2-R): Blinatumomab PK serum concentrations
15. Phase 2 (Cohort Ph2-R): Incidence of anti-blinatumomab antibody formation
16. Phase 2 (Cohort Ph2-M) Key Secondary: CR/CRh with MRD negative response (MRD < 10-4 [0.01%]) within the first 2 cycles
17. Phase 2 (Cohort Ph2-M) Key Secondary: DOR is defined as the time from the first response CR with MRD negative response (MRD < 10-4 [0.01%]) within the first 2 cycles until hematological relapse (including EM relapse) or MRD relapse (MRD ≥ 10-4 [0.01%]) per investigator’s assessment or death due to any cause, whichever occurs first
18. Phase 2 (Cohort Ph2-M): CR/CRh/CRi/Blast free hypoplastic or aplastic BM with MRD negative response (MRD < 10-4 [0.01%]) within the first 2 cycles
19. Phase 2 (Cohort Ph2-M): OS, defined as the time of the start of first dose of SC blinatumomab until death due to any cause
20. Phase 2 (Cohort Ph2-M): Incidence of TEAE, serious TEAE, Treatment related TEAE, and EOI
21. Phase 2 (Cohort Ph2-M): Blinatumomab PK serum concentrations
22. Phase 2 (Cohort Ph2-M): Incidence of anti-blinatumomab antibody formation

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amgen Inc.

Sponsor organisation

Amgen Inc.

Address

1 Amgen Center Drive

City

Thousand Oaks

Postcode

91320-1730

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 7

Locations

3 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Results and documents

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

Documents 25 files

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

Application history

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