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.
* 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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
2 injections of 90Y-DOTA- hLL2 IgG- hLL2 IgG at day -21 and day -14. (The 2 drugs are mixted in the same infusion)
Between the last injection of 90Y-DOTA- hLL2 IgG/hLL2 IgG (J-14) and the allogeneic stem cell transplantation
At Day 0
Determination of the maximum tolerated dose (MTD)
Patient toxicity will be evaluated according to NTCAE V4 criteria.
Time frame: 6 weeks
Overall survival
Time frame: Month 12
Disease free survival at one year post-transplant
Time frame: Month 12
Incidence of relapse at 1 year post-transplant
Time frame: Month 12
Non relapse mortality at day 100 post-transplant
Time frame: Day 100
Non relapse mortality at one year post-transplant
Time frame: Month 12
Hematologic reconstitutions post-transplant
Biological follow-up
Time frame: Month 3
Immune reconstitutions post-transplant
Biological follow-up
Time frame: Month 3
Incidence of acute and chronic GVHD
Time frame: Month 3 and 12
Chimerism post-transplant
Blood sample and/or bone marrow analysis by molecular biology
Time frame: Month 3
Residual disease post-transplant
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Between the last injection of 90Y-DOTA- hLL2 IgG/hLL2 IgG (J-14) and the allogeneic stem cell transplantation
Between the last injection of 90Y-DOTA- hLL2 IgG/hLL2 IgG (J-14) and the allogeneic stem cell transplantation
by flow cytometry analysis
Time frame: Month 3 and Month 12
Toxicity of RIT
biological follow up and physical examination
Time frame: Week 6 and Month 12
Tolerance of RIT
biological follow up and physical examination
Time frame: Week 6 and Month 12
Immunization analysis : detection of antibody anti epratuzumab
By ELISA assay
Time frame: Month 12
90Y-DOTA-Epratuzumab blood pharmacokinetics
Detection of the radioactivity within the patient's blood samples
Time frame: Month 2
Dosage of FLT3-ligand in plasma and correlation with efficacy and toxicity of RIT
by biological assay
Time frame: Month 12