Lymphocyte B CD22 Positive Acute Lymphoblastic Leukemia
Conditions
Keywords
CD22 positive- lymphoblastic leukemia-RIT-Yttrium
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
Interventions
DRUG90Y-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)
DRUGBusulfan
Between the last injection of 90Y-DOTA- hLL2 IgG/hLL2 IgG (J-14) and the allogeneic stem cell transplantation
BIOLOGICALallogeneic stem cell transplantation.
At Day 0
DRUGFludarabine
Between the last injection of 90Y-DOTA- hLL2 IgG/hLL2 IgG (J-14) and the allogeneic stem cell transplantation
BIOLOGICALThymoglobulines
Between the last injection of 90Y-DOTA- hLL2 IgG/hLL2 IgG (J-14) and the allogeneic stem cell transplantation
Sponsors
Nantes University Hospital
Gilead Sciences
Institut Cancerologie de l'Ouest
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determination of the maximum tolerated dose (MTD) | 6 weeks | Patient toxicity will be evaluated according to NTCAE V4 criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Month 3 | Biological follow-up |
| Immune reconstitutions post-transplant | Month 3 | Biological follow-up |
| Incidence of acute and chronic GVHD | Month 3 and 12 | — |
| Chimerism post-transplant | Month 3 | Blood sample and/or bone marrow analysis by molecular biology |
| Residual disease post-transplant | Month 3 and Month 12 | by flow cytometry analysis |
| Toxicity of RIT | Week 6 and Month 12 | biological follow up and physical examination |
| Tolerance 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 |
| 90Y-DOTA-Epratuzumab blood pharmacokinetics | Month 2 | Detection of the radioactivity within the patient's blood samples |
| Dosage of FLT3-ligand in plasma and correlation with efficacy and toxicity of RIT | Month 12 | by biological assay |
Outcome results
None listed