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 (EPRALLO)

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.

Study Overview

• Status: Withdrawn
• Conditions: Lymphocyte B CD22 Positive Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: 90Y-DOTA-Epratuzumab IgG/Epratuzumab IgG; Drug: Busulfan; Biological: allogeneic stem cell transplantation.; Drug: Fludarabine; Biological: Thymoglobulines

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 Type: Interventional
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Collaborators: Gilead Sciences; Institut Cancerologie de l'Ouest

Study record dates

Study Major Dates

• Primary Completion (ACTUAL): January 1, 2017
• Study Completion (ACTUAL): January 1, 2017

Study Registration Dates

• First Submitted: October 2, 2015
• First Submitted That Met QC Criteria: October 13, 2015
• First Posted (ESTIMATE): October 16, 2015

Study Record Updates

• Last Update Posted (ESTIMATE): January 19, 2017
• Last Update Submitted That Met QC Criteria: January 17, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: CD22 positive- lymphoblastic leukemia-RIT-Yttrium
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Epratuzumab; Fludarabine; Busulfan; Thymoglobulin
• Other Study ID Numbers: RC14_0429