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 Overview
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Brief Summary
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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
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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

Conditions
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Lymphocyte B CD22 Positive Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: 90Y-DOTA-Epratuzumab IgG/Epratuzumab IgG
* Drug: Busulfan
* Biological: allogeneic stem cell transplantation.
* Drug: Fludarabine
* Biological: Thymoglobulines


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: 90Y-DOTA-Epratuzumab IgG/Epratuzumab IgG|2 injections of 90Y-DOTA- hLL2 IgG- hLL2 IgG at day -21 and day -14. (The 2 drugs are mixted in the same infusion)|
|Drug: Busulfan|Between the last injection of 90Y-DOTA- hLL2 IgG/hLL2 IgG (J-14) and the allogeneic stem cell transplantation|
|Biological: allogeneic stem cell transplantation.|At Day 0|
|Drug: Fludarabine|Between the last injection of 90Y-DOTA- hLL2 IgG/hLL2 IgG (J-14) and the allogeneic stem cell transplantation|
|Biological: Thymoglobulines|Between the last injection of 90Y-DOTA- hLL2 IgG/hLL2 IgG (J-14) and the allogeneic stem cell transplantation|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of the maximum tolerated dose (MTD) | Patient toxicity will be evaluated according to NTCAE V4 criteria. | 6 weeks | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD22 positive- lymphoblastic leukemia-RIT-Yttrium