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Antiminor Histocompatibility Complex (MiHA) T Cells for Patients With Relapsed Hematologic Malignancies Following Matched HSCT (Guided Lymphocyte Immunopeptide Derived Expansion)

NCT03091933

Description:

This study will evaluate the safety of infusing an anti-MiHA T cell line in patients suffering from an hematologic malignancy that has relapsed following hematopoietic stem cell transplantation from a matched donor.

Related Conditions:
  • Acute Biphenotypic Leukemia
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Chronic Lymphocytic Leukemia
  • Hodgkin Lymphoma
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Antiminor Histocompatibility Complex (MiHA) T Cells for Patients With Relapsed Hematologic Malignancies Following Matched HSCT (Guided Lymphocyte Immunopeptide Derived Expansion)
  • Official Title: An Exploratory, Open-label, Multicenter Study to Evaluate the Safety and Efficacy of Anti-minor Histocompatibility Complex (MiHA) Donor T-lymphocytes Expanded ex Vivo, in Patients With a Hematologic Malignancy, With Molecular or Clinical Relapse After Hematopoietic Stem Cell Transplantation From a Matched Donor

Clinical Trial IDs

  • ORG STUDY ID: CR-MIHA-001
  • NCT ID: NCT03091933

Conditions

  • Hematologic Cancer
  • Relapse Leukemia
  • Relapsed Adult ALL
  • Relapsed Adult AML
  • Relapsed CLL
  • Relapsed Non Hodgkin Lymphoma
  • Relapsed Hodgkin's Lymphoma
  • Relapsed Myelodysplastic Syndromes
  • Relapsed Multiple Myeloma

Interventions

DrugSynonymsArms
GLIDEGLIDE

Purpose

This study will evaluate the safety of infusing an anti-MiHA T cell line in patients suffering from an hematologic malignancy that has relapsed following hematopoietic stem cell transplantation from a matched donor.

Detailed Description

      The GLIDE-201/44 trial primarily aims to test the safety of anti-MiHA T cell line in patients
      suffering from an hematologic malignancy that has relapsed following hematopoietic stem cell
      transplantation from a matched donor. The anti-MiHA T cell lines are derived from the matched
      donor for the patient, the original donor for a given patient. Both the patient and the
      matched donor will undergo screening to determine the expression of targetable MiHAs. Upon
      identification of the target MiHAs, donor cells will be collected through apheresis and
      primed against the selected MiHA. In this setting, the GLIDE 201/44 product will be
      cryopreserved, thawed and administered as a single infusion at a target dose of 4x10E+07
      viable T cells/m2 (range of dose is 0.4 4x10E+07 viable T cells/m2). A second infusion can be
      offered to the patients after an observation period of 42 days upon clinical evaluation by
      the treating physician. In the absence of secondary adverse events following the initial
      infusion, a second infusion of the GLIDE 201/44 product could be administered at a dose level
      up to 3-5 fold the original dose.
    

Trial Arms

NameTypeDescriptionInterventions
GLIDEExperimentalGLIDE single infusion at a target dose of 4x107 viable T-cells/m2

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Prior allogeneic HLA-matched stem cell transplantation
    
              -  Any of the following hematologic malignancies:
    
              -  Acute myeloid leukemia (AML)
    
              -  Acute lymphoblastic leukemia (ALL)
    
              -  Biphenotypic leukemia
    
              -  Chronic lymphoblastic leukemia (CLL)
    
              -  Hodgkin Lymphoma
    
              -  Non-Hodgkin Lymphoma (NHL)
    
              -  Multiple Myeloma (MM)
    
              -  Myelodysplastic syndrome (MDS)
    
              -  Presence of HLA2:01 and / or HLA44:02 and / or HLA-B*44:03, HLA-A*01:01; HLA-A*03:01;
                 HLA-A*11:01;HLA A*24:02; HLA-A*29:02; HLA-A*32:01; HLA-B*07:02; HLA-B*08:01; HLA
                 B*13:02; HLA-B*14:02; HLA-B*15:01; HLA-B*18:01; HLA-B*27:05; HLA B*35:01; HLA-B*40:01;
                 or HLA-B*57:01
    
              -  At least 6 months after allogeneic hematopoietic stem cell transplantation
    
              -  Presence of detectable malignant disease post-transplantation in the form of
                 molecular, cytogenetic or hematologic relapse of the malignant disorder.
    
              -  Eligible to receive cytoreductive chemotherapy
    
              -  Original stem cell donor available for leukocyte donation.
    
              -  ECOG performance status ≤2.
    
              -  Ability to provide written consent.
    
              -  Accessible for treatment and follow up.
    
              -  Presence of a targetable MiHA based on exome sequencing of the patient and donor
    
            Exclusion Criteria:
    
              -  Active acute GVHD > grade I
    
              -  Prior grade III-IV acute GVHD within the last year
    
              -  Uncontrolled chronic GVHD
    
              -  Prior administration of donor lymphocyte infusion (DLI)
    
              -  Use of T-cell depleting antibodies in the previous 30 days
    
              -  Treatment with immune suppressors (oral or parenteral steroids corresponding to a dose
                 of prednisone greater than 7.5 mg/day, calcineurine inhibitors, rapamycin,
                 mycophenolate mofetil, etc) during the last 30 days.
    
              -  Uncontrolled active infection
    
              -  Uncontrolled central nervous system involvement by leukemia cells (blasts).
    
              -  AST or ALT > 2.5 x ULN (CTCAE grade 2)
    
              -  Bilirubin > 1.5 x ULN (CTCAE grade 2)
    
              -  Creatinine clearance < 50 mL/min
    
              -  Positive test for human immunodeficiency virus (HIV)
    
              -  Positive pregnancy test (women of childbearing age only)
    
              -  Lactating women: the safety of this therapy on breast milk is not known.
    
              -  Estimated probability of surviving less than 3 months
    
              -  Known allergy to any of the components of GLIDE (e.g., dimethyl sulfoxide)
    
              -  Intercurrent illness or medical condition precluding safe administration of the
                 planned protocol treatment or required follow-up.
          
    Maximum Eligible Age:65 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Non-hematologic toxicity related to GLIDE post injection
    Time Frame:6 months
    Safety Issue:
    Description:No death or other toxic events directly related to GLIDE injection

    Secondary Outcome Measures

    Measure:Response of hematologic malignancy (acute leukemia (ALL, AML, biphenotypic), CLL, HL, NHL, MM or MDS) post-injection
    Time Frame:up to 12 months
    Safety Issue:
    Description:Disease progression following GLIDE injection
    Measure:Incidence and severity of acute and chronic graft versus host disease (GvHD)
    Time Frame:up to 12 months
    Safety Issue:
    Description:Progression (if any) or induction of GvHD
    Measure:Persistence of GLIDE in the host and homing to peripheral blood, bone marrow and other tissues
    Time Frame:up to 12 months
    Safety Issue:
    Description:Monitoring of GLIDE product persistence in host
    Measure:Non-Relapse mortality (NRM)
    Time Frame:up to 12 months
    Safety Issue:
    Description:Time to deaths without relapse/recurrence
    Measure:Relapse-incidence (RI)
    Time Frame:up to 12 months
    Safety Issue:
    Description:Time to relapse
    Measure:Overall survival (OS)
    Time Frame:up to 12 months
    Safety Issue:
    Description:Time to death, irrespective of the cause
    Measure:Progression-free survival (PFS)
    Time Frame:up to 12 months
    Safety Issue:
    Description:It is time to any of the following: OS, RI, NRM, Time to relapse, Relapse free survival

    Details

    Phase:Phase 1/Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Ciusss de L'Est de l'Île de Montréal

    Trial Keywords

    • allogeneic hematopoietic stem cell transplantation
    • relapsed hematopoietic malignancy
    • HLA matched donor
    • minor histocompatibilty antigen (MiHA)

    Last Updated