Testing a Reduced Conditioning Regimen FB2A2 Preceded by a Fractionated Radio-immunotherapy (RIT) With 90Y-Epratuzumab Before Allogeneic Stem Cell Transplantation for Patients With Lymphocyte B CD22 Positive Acute Lymphoblastic Leukemia

Phase 1

Withdrawn

• Conditions: Lymphocyte B CD22 Positive Acute Lymphoblastic Leukemia

• Registration Number: NCT02577094
• Lead Sponsor: Nantes University Hospital

Brief Summary

Determination of the maximum tolerated dose (MTD) of fractionated RIT with epratuzumab radiolabeled with yttrium-90 (90Y-epratuzumab) preceding a reduced conditioning regimen FB2A2 before allogeneic stem cell transplantation.

Detailed Description

* Physical examination (screening and follow-up)

* Complete blood counts (screening and follow-up)

* Dosage of FLT3-ligand in plasma (screening and follow-up)

* Blood ionogramme, creatinine hepatic work-up (screening and follow-up)

* Left ventricular ejection fraction at pre-implant assessment

* Immunization test (screening and follow-up)

* Bone marrow aspiration or/and blood CD 22 immunophenotype for minimal residual disease evaluation (screening and follow-up)

* All exams which were initially abnormal and which are necessary for response evaluation and All exams which are needed in case of relapse suspicion.

* Pharmacokinetic of 90Y-hLL2

Study Timeline

• Study First Submitted: 2015-10-02
• Study First Submitted QC: 2015-10-13
• Study First Posted: 2015-10-16
• Status Verified: 2017-01
• Primary Completion: 2017-01
• Study Completion: 2017-01
• Last Update Submitted: 2017-01-17
• Last Update Posted: 2017-01-19

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Age ≥ 18
• Acute lymphoblastic Leukemia (ALL) CD22 + B-type in RC1 with high risk
• B-Cell Acute Lymphoblastic Leukemia (ALL) CD22+ beyond RC1.
• Expression of CD22 ≥ 30% in tumor population evaluated by flow cytometry or immunohistochemistry at diagnosis stage or relapse stage.
• HLA-identical donor intra family or not, without major HLA mismatch (9 / 10th accepted) without contra-indication for stem cell mobilization
• ECOG (Eastern Cooperative Oncology Group) ≤ 2
• Having or not received previously Epratuzumab
• Eligible for an allograft with reduced conditioning regimen
• With a signed informed consent
• Patient in age of children bearing with adequate contraception
• Patient affiliated to or beneficiary of the National Health Service

Exclusion Criteria

• T-cell ALL
• Known hypersensibility to 90Y-DOTA-hLL2
• Immunization against hLL2 for patients having already received one or several injections of this antibody
• Patient eligible for myeloablative conditioning regimen
• Other prior malignancies must have had at least a 2-year disease-free interval with the exception of successfully treated carcinoma skin cancer or carcinoma in situ of the cervix.
• Patient with progressive psychiatric condition.
• HIV positive, hepatitis B-antigen positive, or hepatitis C positive patients who need a treatment
• Pregnant or breast-feeding women
• Women with childbearing potential without effective contraception
• Serious concomitant and uncontrolled infection
• Usual contraindications in the allogeneic transplant:
• Adult patient protected by the French law

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Determination of the maximum tolerated dose (MTD)	6 weeks	Patient toxicity will be evaluated according to NTCAE V4 criteria.

Secondary Outcome Measures

Name	Time	Method
Incidence of relapse at 1 year post-transplant	Month 12
Hematologic reconstitutions post-transplant	Month 3	Biological follow-up
Residual disease post-transplant	Month 3 and Month 12	by flow cytometry analysis
Overall survival	Month 12
Non relapse mortality at day 100 post-transplant	Day 100
Disease free survival at one year post-transplant	Month 12
Non relapse mortality at one year post-transplant	Month 12
Immune reconstitutions post-transplant	Month 3	Biological follow-up
Incidence of acute and chronic GVHD	Month 3 and 12
Toxicity of RIT	Week 6 and Month 12	biological follow up and physical examination
Immunization analysis : detection of antibody anti epratuzumab	Month 12	By ELISA assay
Dosage of FLT3-ligand in plasma and correlation with efficacy and toxicity of RIT	Month 12	by biological assay
Chimerism post-transplant	Month 3	Blood sample and/or bone marrow analysis by molecular biology
Tolerance of RIT	Week 6 and Month 12	biological follow up and physical examination
90Y-DOTA-Epratuzumab blood pharmacokinetics	Month 2	Detection of the radioactivity within the patient's blood samples