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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)

Primary Purpose

Lymphocyte B CD22 Positive Acute Lymphoblastic Leukemia

Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
90Y-DOTA-Epratuzumab IgG/Epratuzumab IgG
Busulfan
allogeneic stem cell transplantation.
Fludarabine
Thymoglobulines
Sponsored by
Nantes University Hospital
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphocyte B CD22 Positive Acute Lymphoblastic Leukemia focused on measuring CD22 positive- lymphoblastic leukemia-RIT-Yttrium

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Outcomes

    Primary Outcome Measures

    Determination of the maximum tolerated dose (MTD)
    Patient toxicity will be evaluated according to NTCAE V4 criteria.

    Secondary Outcome Measures

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

    Full Information

    First Posted
    October 2, 2015
    Last Updated
    January 17, 2017
    Sponsor
    Nantes University Hospital
    Collaborators
    Gilead Sciences, Institut Cancerologie de l'Ouest
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02577094
    Brief Title
    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
    Acronym
    EPRALLO
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2017
    Overall Recruitment Status
    Withdrawn
    Study Start Date
    undefined (undefined)
    Primary Completion Date
    January 2017 (Actual)
    Study Completion Date
    January 2017 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Nantes University Hospital
    Collaborators
    Gilead Sciences, Institut Cancerologie de l'Ouest

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    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

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Lymphocyte B CD22 Positive Acute Lymphoblastic Leukemia
    Keywords
    CD22 positive- lymphoblastic leukemia-RIT-Yttrium

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Intervention Type
    Drug
    Intervention Name(s)
    90Y-DOTA-Epratuzumab IgG/Epratuzumab IgG
    Other Intervention Name(s)
    90Y-DOTA- hLL2 IgG and hLL2 IgG
    Intervention Description
    2 injections of 90Y-DOTA- hLL2 IgG- hLL2 IgG at day -21 and day -14. (The 2 drugs are mixted in the same infusion)
    Intervention Type
    Drug
    Intervention Name(s)
    Busulfan
    Intervention Description
    Between the last injection of 90Y-DOTA- hLL2 IgG/hLL2 IgG (J-14) and the allogeneic stem cell transplantation
    Intervention Type
    Biological
    Intervention Name(s)
    allogeneic stem cell transplantation.
    Intervention Description
    At Day 0
    Intervention Type
    Drug
    Intervention Name(s)
    Fludarabine
    Intervention Description
    Between the last injection of 90Y-DOTA- hLL2 IgG/hLL2 IgG (J-14) and the allogeneic stem cell transplantation
    Intervention Type
    Biological
    Intervention Name(s)
    Thymoglobulines
    Intervention Description
    Between the last injection of 90Y-DOTA- hLL2 IgG/hLL2 IgG (J-14) and the allogeneic stem cell transplantation
    Primary Outcome Measure Information:
    Title
    Determination of the maximum tolerated dose (MTD)
    Description
    Patient toxicity will be evaluated according to NTCAE V4 criteria.
    Time Frame
    6 weeks
    Secondary Outcome Measure Information:
    Title
    Overall survival
    Time Frame
    Month 12
    Title
    Disease free survival at one year post-transplant
    Time Frame
    Month 12
    Title
    Incidence of relapse at 1 year post-transplant
    Time Frame
    Month 12
    Title
    Non relapse mortality at day 100 post-transplant
    Time Frame
    Day 100
    Title
    Non relapse mortality at one year post-transplant
    Time Frame
    Month 12
    Title
    Hematologic reconstitutions post-transplant
    Description
    Biological follow-up
    Time Frame
    Month 3
    Title
    Immune reconstitutions post-transplant
    Description
    Biological follow-up
    Time Frame
    Month 3
    Title
    Incidence of acute and chronic GVHD
    Time Frame
    Month 3 and 12
    Title
    Chimerism post-transplant
    Description
    Blood sample and/or bone marrow analysis by molecular biology
    Time Frame
    Month 3
    Title
    Residual disease post-transplant
    Description
    by flow cytometry analysis
    Time Frame
    Month 3 and Month 12
    Title
    Toxicity of RIT
    Description
    biological follow up and physical examination
    Time Frame
    Week 6 and Month 12
    Title
    Tolerance of RIT
    Description
    biological follow up and physical examination
    Time Frame
    Week 6 and Month 12
    Title
    Immunization analysis : detection of antibody anti epratuzumab
    Description
    By ELISA assay
    Time Frame
    Month 12
    Title
    90Y-DOTA-Epratuzumab blood pharmacokinetics
    Description
    Detection of the radioactivity within the patient's blood samples
    Time Frame
    Month 2
    Title
    Dosage of FLT3-ligand in plasma and correlation with efficacy and toxicity of RIT
    Description
    by biological assay
    Time Frame
    Month 12

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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

    12. IPD Sharing Statement

    Learn more about this trial

    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

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