Trial aimed at examinate the functionality and effectiveness of the drug "IO" in adult patients with a rare form of cancer that affect the cells from which the white blood cells (cells present in the blood) originate before being subjected to a medical procedure used in hematology known as transplantation, which leads to the replacement of the cells from which the blood originates.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Gimema Franco Mandelli Onlus

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

30 Oct 2019 → ongoing

Decision date (initial)

2024-12-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Fondazione GIMEMA Franco Mandelli Onlus · Pfizer S.R.L.

External identifiers

EU CT number

2023-510516-39-00

EudraCT number

2018-003006-32

ClinicalTrials.gov

NCT03610438

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety, Others

The primary objective of the study is to determine effectiveness of Inotuzumab in obtaining MRD negativity in MRD positive ALL patients.

Secondary objectives 3

1. Establish survival of the treatment population
2. Define treatment safety and incidence of adverse events in MRD positive population
3. Define the number of patient that will have a bridge to transplant with Inotuzumab (considering only patients that could be transplanted)

Conditions and MedDRA coding

Acute B-cell Lymphoblastic Leukemia with minimal residual positive disease prior to haematopoietic stem cell transplantation in adult patients

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. To be classified as having ALL according to WHO classification of haematological neoplasms, patients must have >20% blasts in bone marrow at the time of diagnosis
2. Blasts at the diagnosis or in any timepoint had to be CD22+
3. To have a measurable BCR-ABL1 fusion transcript (cohort 1) or a measurable IG/TCR specific rearrangement (cohort 2)
4. To have any measurable MRD positivity after at least: a. 3 months of therapy for Ph+ ALL, or the failure of at least 2nd line TKI (cohort 1) b. 2 courses of therapy for Ph- ALL (cohort 2)
5. and to not have more than 5% of bone marrow blasts. Patients has to be in 1st or 2nd complete remission.
6. Patients = 18 years old with no upper age limit
7. Patients with a life expectancy >12 weeks
8. Adequate hepatic function as defined by the following criteria: a. total serum bilirubin =1.5 x upper limit of normal (ULN), unless due to Gilbert’s syndrome b. alanine aminotransferase (ALT) =2.5 × ULN c. aspartate aminotransferase (AST) =2.5 × ULN
9. Adequate pancreatic function as defined by the following criterion: a. serum lipase and amylase =1.5 × ULN
10. For females of childbearing potential, a negative pregnancy test must be documented at Screening
11. Female and male patients who are fertile should use an effective form of contraception with their sexual partners from screening through 4 months after the end of treatment. As a precautionary measure, breast-feeding should be discontinued during treatment with Inotuzumab and should not be restarted after discontinuation of Inotuzumab. Male patients must agree to refrain from sperm donation, from initial treatment administration until 12 months after the last dose of study drug
12. Signed written informed consent according to ICH/EU/GCP and national local laws.

Exclusion criteria 21

1. More than 5% of BM blasts
2. WHO performance status = 50% (Karnofsky) or = 3 (ECOG)
3. Active HBV or HCV hepatitis, or AST/ALT = 2.5 x ULN and bilirubine = 1.5 x ULN
4. Evidence of liver fibrosis, portal hypertension or other clinically relevant liver abnormalities at screening liver ultrasonography
5. History of alcohol abuse
6. Burkitt lymphoma and active CNS leukemia. Patients with previuos neurological toxicitiy as well comorbidity will be carefully evaluated for enrolment
7. Ongoing or active infections
8. Uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL)
9. Clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to: a. any history of myocardial infarction, stroke, or revascularization b. unstable angina or transient ischemic attack within 6 months prior to enrollment c. congestive heart failure within 6 months prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards within 6 months prior to enrollment d. history of clinically significant (as determined by the treating physician) atrial arrhythmia e. any history of ventricular arrhythmia f. any history of venous thromboembolism including deep venous thrombosis or pulmonary embolism;
10. Uncontrolled hypertension (diastolic blood pressure >90 mm Hg; systolic >140 mm Hg). Patients with hypertension should be under treatment on study entry to effect blood pressure control
11. Creatinine level > 2.5mg/dl or Glomerular Filtration Rate (GFR) < 20 ml/min or proteinuria > 3.5 g/day
12. Documented inherited protrombotic disorders
13. Patients who have received any investigational drug = 4 weeks
14. Patients who have undergone major surgery = 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy;
15. Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention or with a life expectancy due to other malignancy <6 months
16. Patients that have received Inotuzumab or Anti CD22 directed therapies before
17. Patients with known hereditary coagulopathy
18. Patient that received during their life diagnosis of VOD or had ongoing VOD
19. Patients with hypersensitivity to the active substance or to any of the excipients (Sucrose, Polysorbate 80, Sodium chloride, tromethamine)
20. Patients who are pregnant or breast feeding and adults of reproductive potential not employing an effective method of birth control (women of childbearing potential must have a negative serum pregnancy test within 48 hrs prior to administration of induction therapy). Post menopausal women must be amenorrhoic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 4 months following discontinuation of study drugs. Fertile patients will be advised to adopt contraceptive methods while on treatment
21. Patients unwilling or unable to comply with the protocol

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary end point is % of MRD negativity after course 2 (or course 1 if will be performed only course1).

Secondary endpoints 10

1. Molecular Disease Progression: defined as the rise of more than 2 log in MRD from any previous determination
2. Disease Progression: this is also equivalent to Treatment Failure, Lack of Efficacy, or No Response.
3. Overall Survival (OS), defined as the number of days between the first study drug administration and death from any cause or lost to follow up.
4. Event Free Survival (EFS), defined as the number of days between the first study drug administration and any event including disease progressionor death.
5. DFS (Disease Free Survival), defined as the interval between the date of response achievement and the date of death, relapse or last follow-up.
6. Incidence time and nature of any adverse event.
7. Severe effect related to treatment safety is defined as an adverse event occurring within the first cycle, judged to be related to treatment and meeting any of the following criteria: o Grade 3 non-hematological toxicity lasting more than 7 days. o Grade 4 non-hematological toxicity.
8. Incidence, severity, seriousness and treatment-causality of Treatment Emergent Signs and Symptoms.
9. Frequency of clinically significant abnormalities in physical examination, safety laboratory tests, vital signs and 12-Lead ECG.
10. VOD occurred during or after protocol or transplant procedures for up to 2 years.

Investigational products

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

Test 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Gimema Franco Mandelli Onlus

Sponsor organisation

Fondazione Gimema Franco Mandelli Onlus

Address

Via Casilina 5

City

Rome

Postcode

00182

Country

Italy

Scientific contact point

Organisation

Fondazione Gimema Franco Mandelli Onlus

Contact name

CENTRO DATI

Public contact point

Organisation

Fondazione Gimema Franco Mandelli Onlus

Contact name

CENTRO DATI

Third parties 4

Locations

1 EU/EEA country · 41 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 17 files

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

Application history

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