Clinical Trials /

Safety and Efficacy of ATIR101 as Adjunctive Treatment to Blood Stem Cell Transplantation From a Haploidentical Family Donor Compared to Post-transplant Cyclophosphamide in Patients With Blood Cancer

NCT02999854

Description:

The primary objective of this study is to compare safety and efficacy of a haploidentical T-cell depleted HSCT and adjunctive treatment with ATIR101 versus a haploidentical T cell replete HSCT with post-transplant administration of high dose cyclophosphamide (PTCy) in patients with a hematologic malignancy. An additional objective of the study is to compare the effect of the two treatments on quality of life.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Safety and Efficacy of ATIR101 as Adjunctive Treatment to Blood Stem Cell Transplantation From a Haploidentical Family Donor Compared to Post-transplant Cyclophosphamide in Patients With Blood Cancer
  • Official Title: A Phase III, Multicenter, Randomized Controlled Study to Compare Safety and Efficacy of a Haploidentical HSCT and Adjunctive Treatment With ATIR101, a T-lymphocyte Enriched Leukocyte Preparation Depleted ex Vivo of Host Alloreactive T-cells, Versus a Haploidentical HSCT With Post-transplant Cyclophosphamide in Patients With a Hematologic Malignancy

Clinical Trial IDs

  • ORG STUDY ID: CR-AIR-009
  • SECONDARY ID: 2016-004672-21
  • NCT ID: NCT02999854

Conditions

  • Acute Myeloid Leukemia
  • Acute Lymphoblastic Leukemia
  • Myelodysplastic Syndrome

Interventions

DrugSynonymsArms
ATIR101ATIR101
CyclophosphamidePTCy

Purpose

The primary objective of this study is to compare safety and efficacy of a haploidentical T-cell depleted HSCT and adjunctive treatment with ATIR101 versus a haploidentical T cell replete HSCT with post-transplant administration of high dose cyclophosphamide (PTCy) in patients with a hematologic malignancy. An additional objective of the study is to compare the effect of the two treatments on quality of life.

Detailed Description

      Study CR-AIR-009 is a Phase III randomized controlled multicenter open-label study comparing
      two parallel groups. After signing informed consent, a total of 250 patients will be
      randomized in a 1:1 fashion to receive either a T-cell depleted hematopoietic stem cell
      transplantation (HSCT; CD34 selection) from a related, haploidentical donor, followed by
      ATIR101 infusion, or a T-cell replete HSCT, followed by a high dose of post-transplant
      cyclophosphamide (PTCy).

      Randomization will use minimization to balance treatment groups with respect to underlying
      disease (AML, ALL, or MDS), Disease Risk Index (DRI; intermediate risk, high risk, or very
      high risk) and center. A stochastic treatment allocation procedure will be used so that the
      treatment assignment is random for all patients entered in the study.

      Patients randomized in the ATIR101 group will receive a single ATIR101 dose of 2×10E6 viable
      T-cells/kg between 28 and 32 days after the HSCT. Patients randomized in the PTCy group will
      receive cyclophosphamide 50 mg/kg/day at 3 and 4/5 days after the HSCT. All patients will be
      followed up for at least 24 months post HSCT.
    

Trial Arms

NameTypeDescriptionInterventions
ATIR101ExperimentalT-cell depleted HSCT from a related, haploidentical donor, followed by IV infusion with ATIR101 at a single dose of 2×10E6 viable T-cells/kg body weight between 28 and 32 days after the HSCT
    PTCyActive ComparatorT-cell replete HSCT from a related, haploidentical donor, followed by IV infusion of post-transplant cyclophosphamide (PTCy) 50 mg/kg/day at 3 and 4/5 days after the HSCT
    • Cyclophosphamide

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Any of the following hematologic malignancies:
    
                   -  Acute myeloid leukemia (AML) in first cytomorphological remission (with < 5%
                      blasts in the bone marrow) with Disease Risk Index (DRI) intermediate or above,
                      or in second or higher cytomorphological remission (with < 5% blasts in the bone
                      marrow)
    
                   -  Acute lymphoblastic leukemia (ALL) in first or higher remission (with < 5% blasts
                      in the bone marrow)
    
                   -  Myelodysplastic syndrome (MDS): transfusion-dependent (requiring at least one
                      transfusion per month), or intermediate or higher Revised International
                      Prognostic Scoring System (IPSS-R) risk group
    
              -  Clinical justification of allogeneic stem cell transplantation where a suitable HLA
                 matched sibling or unrelated donor is unavailable in a timely manner
    
              -  Availability of a related haploidentical donor with one fully shared haplotype and 2
                 to 4 mismatches at the HLA-A, -B, -C, and -DRB1 loci of the unshared haplotype, as
                 determined by high resolution human leukocyte antigen (HLA)-typing
    
              -  Karnofsky Performance Status (KPS) ≥ 70%
    
              -  Male or female, age ≥ 18 years and ≤ 70 years. Patients aged ≥ 65 years must have a
                 Sorror score ≤ 3
    
              -  Patient weight ≥ 25 kg and ≤ 130 kg
    
              -  Availability of a donor aged ≥ 16 years and ≤ 75 years who is eligible according to
                 local requirements and regulations. Donors aged < 16 years are allowed if they are the
                 only option for an HSCT, if they are permitted by local regulations, and if the
                 IRB/IEC approves participation in the study.
    
              -  For females of childbearing potential who are sexually active and males who have
                 sexual contact with a female of childbearing potential: willingness to use of reliable
                 methods of contraception (oral contraceptives, intrauterine device, hormone implants,
                 contraceptive injection or abstinence) during study participation
    
              -  Given written informed consent (patient and donor)
    
            Exclusion Criteria:
    
              -  Diagnosis of chronic myelomonocytic leukemia (CMML)
    
              -  Availability of a suitable HLA-matched sibling or unrelated donor in a donor search
    
              -  Prior allogeneic hematopoietic stem cell transplantation
    
              -  Diffusing capacity for carbon monoxide (hemoglobin corrected DLCO) < 50% predicted
    
              -  Left ventricular ejection fraction < 45% (evaluated by echocardiogram or MUGA scan)
    
              -  Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2.5 × upper
                 limit of normal (CTCAE grade 2)
    
              -  Creatinine clearance < 50 ml/min (calculated or measured)
    
              -  Positive pregnancy test or breastfeeding of patient or donor (women of childbearing
                 age only)
    
              -  Estimated probability of surviving less than 3 months
    
              -  Known allergy to any of the components of ATIR101 (e.g., dimethyl sulfoxide)
    
              -  Known hypersensitivity to cyclophosphamide or any of its metabolites
    
              -  Any contraindication for GVHD prophylaxis with mycophenolate mofetil, cyclosporine A,
                 or tacrolimus
    
              -  Known presence of HLA antibodies against the non-shared donor haplotype
    
              -  Positive viral test of the patient or donor for human immunodeficiency virus (HIV)-1,
                 HIV-2, hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum, human
                 T-lymphotropic virus (HTLV)-1 (if tested), HTLV-2 (if tested), West Nile virus (WNV;
                 if tested), or Zika virus (if tested)
    
              -  Any other condition that, in the opinion of the investigator, makes the patient or
                 donor ineligible for the study
          
    Maximum Eligible Age:70 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Graft-versus-host disease-free, relapse-free survival (GRFS)
    Time Frame:Through study completion, at least two years post HSCT
    Safety Issue:
    Description:Time from randomization until grade III/IV acute GVHD, chronic GVHD requiring systemic immunosuppressive treatment, disease relapse, or death, whichever occurs first

    Secondary Outcome Measures

    Measure:Overall survival (OS)
    Time Frame:Through study completion, at least two years post HSCT
    Safety Issue:
    Description:Time from randomization until death from any cause
    Measure:Progression-free survival (PFS)
    Time Frame:Through study completion, at least two years post HSCT
    Safety Issue:
    Description:Time from randomization until relapse, disease progression, or death, whichever occurs first
    Measure:Relapse-related mortality (RRM)
    Time Frame:Through study completion, at least two years post HSCT
    Safety Issue:
    Description:Time from randomization to death due to disease relapse or disease progression
    Measure:Transplant-related mortality (TRM)
    Time Frame:Through study completion, at least two years post HSCT
    Safety Issue:
    Description:Time from randomization to death due to causes other than disease relapse or disease progression

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Kiadis Pharma

    Trial Keywords

    • Haploidentical stem cell transplantation
    • Graft-versus-host disease
    • Immune reconstitution
    • Alloreactive T-cells
    • Photodynamic treatment
    • Hematologic malignancy
    • Transplant-related mortality
    • Overall survival
    • GRFS
    • GVHD

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