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

Sponsor

Ciusss de L'Est de l'Île de Montréal (Other)

Overall Status

Unknown status

CT.gov ID

NCT03091933

Collaborator

(none)

Enrollment

Location

Arm

25.7

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
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	Biological: GLIDE	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

exploratory, open-labelexploratory, open-label

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Feb 6, 2017

Anticipated Primary Completion Date :

Mar 31, 2018

Anticipated Study Completion Date :

Mar 31, 2019

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Non-hematologic toxicity related to GLIDE post injection [6 months]
No death or other toxic events directly related to GLIDE injection

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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-B44:03, HLA-A01:01; HLA-A03:01; HLA-A11:01;HLA A24:02; HLA-A29:02; HLA-A32:01; HLA-B07:02; HLA-B08:01; HLA B13:02; HLA-B14:02; HLA-B15:01; HLA-B18:01; HLA-B27:05; HLA B35:01; HLA-B40:01; 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CIUSSS d l'Est-de-l'Île-de-Montréal	Montreal	Quebec	Canada	H1T 2M4

Sponsors and Collaborators

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