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

December 4, 2017 updated by: Ciusss de L'Est de l'Île de Montréal

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H1T 2M4
        • Recruiting
        • CIUSSS d l'Est-de-l'Île-de-Montréal
        • Contact:
        • Contact:
        • Principal Investigator:
          • Denis-Claude Roy, MD PhD
        • Sub-Investigator:
          • Jean-Sébastien Delisle, MD PhD
        • Sub-Investigator:
          • Silvy Lachance, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: GLIDE
GLIDE single infusion at a target dose of 4x107 viable T-cells/m2
Biological: GLIDE
Gudide Lymphocyte by Immunopeptide Derived Expansion (GLIDE) is an anti- Minor histocompatibility (MiHA) cell line

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ciusss de L'Est de l'Île de Montréal

Investigators

  • Principal Investigator: Denis-Claude Roy, MD PhD, CIUSSS d l'Est-de-l'Île-de-Montréal
  • Principal Investigator: Jean-Sébastien Delisle, MD PhD, CIUSSS d l'Est-de-l'Île-de-Montréal
  • Principal Investigator: Silvy Lachance, MD, CIUSSS d l'Est-de-l'Île-de-Montréal

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 6, 2017

Primary Completion (Anticipated)

March 31, 2018

Study Completion (Anticipated)

March 31, 2019

Study Registration Dates

First Submitted

March 21, 2017

First Submitted That Met QC Criteria

March 21, 2017

First Posted (Actual)

March 27, 2017

Study Record Updates

Last Update Posted (Actual)

December 6, 2017

Last Update Submitted That Met QC Criteria

December 4, 2017

Last Verified

December 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR-MIHA-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

IPD Plan Description

De-identified individual participant data for all primary and secondary outcome measures will be made available within 6 months of study end

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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