Clinical trial NCT02577094: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Lymphocyte B CD22 Positive Acute Lymphoblastic Leukemia
Keywords: CD22 positive- lymphoblastic leukemia-RIT-Yttrium
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
name: Institut Cancerologie de l'Ouest
First posted: 2015-10-16
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Determination of the maximum tolerated dose (MTD)
timeFrame: 6 weeks
Secondary outcomes:
measure: Overall survival
timeFrame: Month 12
measure: Disease free survival at one year post-transplant
timeFrame: Month 12
measure: Incidence of relapse at 1 year post-transplant
timeFrame: Month 12
measure: Non relapse mortality at day 100 post-transplant
timeFrame: Day 100
measure: Non relapse mortality at one year post-transplant
timeFrame: Month 12
measure: Hematologic reconstitutions post-transplant
timeFrame: Month 3
measure: Immune reconstitutions post-transplant
timeFrame: Month 3
measure: Incidence of acute and chronic GVHD
timeFrame: Month 3 and 12
measure: Chimerism post-transplant
timeFrame: Month 3
measure: Residual disease post-transplant
timeFrame: Month 3 and Month 12
measure: Toxicity of RIT
timeFrame: Week 6 and Month 12
measure: Tolerance of RIT
timeFrame: Week 6 and Month 12
measure: Immunization analysis : detection of antibody anti epratuzumab
timeFrame: Month 12
measure: 90Y-DOTA-Epratuzumab blood pharmacokinetics
timeFrame: Month 2
measure: Dosage of FLT3-ligand in plasma and correlation with efficacy and toxicity of RIT
timeFrame: Month 12
Other outcomes:
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