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

Primary Purpose

Hematologic Cancer, Relapse Leukemia, Relapsed Adult ALL

Status

Unknown status

Phase

Phase 1

Locations

Canada

Study Type

Interventional

Intervention

GLIDE

About this trial

This is an interventional treatment trial for Hematologic Cancer focused on measuring allogeneic hematopoietic stem cell transplantation, relapsed hematopoietic malignancy, HLA matched donor, minor histocompatibilty antigen (MiHA)

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept 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-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.

Sites / Locations

CIUSSS d l'Est-de-l'Île-de-MontréalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

GLIDE

Arm Description

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

Outcomes

Primary Outcome Measures

Non-hematologic toxicity related to GLIDE post injection

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

Disease progression following GLIDE injection

Incidence and severity of acute and chronic graft versus host disease (GvHD)

Progression (if any) or induction of GvHD

Persistence of GLIDE in the host and homing to peripheral blood, bone marrow and other tissues

Monitoring of GLIDE product persistence in host

Non-Relapse mortality (NRM)

Time to deaths without relapse/recurrence

Relapse-incidence (RI)

Time to relapse

Overall survival (OS)

Time to death, irrespective of the cause

Progression-free survival (PFS)

It is time to any of the following: OS, RI, NRM, Time to relapse, Relapse free survival

Full Information

NCT ID

NCT03091933

First Posted

March 21, 2017

Last Updated

December 4, 2017

Sponsor

Ciusss de L'Est de l'Île de Montréal

1. Study Identification

Unique Protocol Identification Number

NCT03091933

Brief Title

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

Acronym

GLIDE

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2017

Overall Recruitment Status

Unknown status

Study Start Date

February 6, 2017 (Actual)

Primary Completion Date

March 31, 2018 (Anticipated)

Study Completion Date

March 31, 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Ciusss de L'Est de l'Île de Montréal

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Model Description

exploratory, open-label

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

GLIDE

Arm Type

Experimental

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

GLIDE

Intervention Description

Gudide Lymphocyte by Immunopeptide Derived Expansion (GLIDE) is an anti- Minor histocompatibility (MiHA) cell line

Primary Outcome Measure Information:

Title

Non-hematologic toxicity related to GLIDE post injection

Description

No death or other toxic events directly related to GLIDE injection

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Response of hematologic malignancy (acute leukemia (ALL, AML, biphenotypic), CLL, HL, NHL, MM or MDS) post-injection

Description

Disease progression following GLIDE injection

Time Frame

up to 12 months

Title

Incidence and severity of acute and chronic graft versus host disease (GvHD)

Description

Progression (if any) or induction of GvHD

Time Frame

up to 12 months

Title

Persistence of GLIDE in the host and homing to peripheral blood, bone marrow and other tissues

Description

Monitoring of GLIDE product persistence in host

Time Frame

up to 12 months

Title

Non-Relapse mortality (NRM)

Description

Time to deaths without relapse/recurrence

Time Frame

up to 12 months

Title

Relapse-incidence (RI)

Description

Time to relapse

Time Frame

up to 12 months

Title

Overall survival (OS)

Description

Time to death, irrespective of the cause

Time Frame

up to 12 months

Title

Progression-free survival (PFS)

Description

It is time to any of the following: OS, RI, NRM, Time to relapse, Relapse free survival

Time Frame

up to 12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jean-Guy Némorin, PhD

Phone

(514) 252-3400

Ext

6247

jgnemorin@centrec3i.com

First Name & Middle Initial & Last Name or Official Title & Degree

Stéphanie Thiant, PhD

Phone

(514) 252-3400

Ext

4681

sthiant.hmr@ssss.gouv.qc.ca

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Denis-Claude Roy, MD PhD

Organizational Affiliation

CIUSSS d l'Est-de-l'Île-de-Montréal

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Jean-Sébastien Delisle, MD PhD

Organizational Affiliation

CIUSSS d l'Est-de-l'Île-de-Montréal

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Silvy Lachance, MD

Organizational Affiliation

CIUSSS d l'Est-de-l'Île-de-Montréal

Official's Role

Principal Investigator

Facility Information:

Facility Name

CIUSSS d l'Est-de-l'Île-de-Montréal

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H1T 2M4

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jean-Guy Némorin, PhD

Phone

514-252-3400

Ext

6247

jgnemorin@centrec3i.com

First Name & Middle Initial & Last Name & Degree

Stéphanie Thiant, PhD

Phone

214-252-3400

Ext

4681

sthiant.hmr@ssss.gouv.qc.ca

First Name & Middle Initial & Last Name & Degree

Denis-Claude Roy, MD PhD

First Name & Middle Initial & Last Name & Degree

Jean-Sébastien Delisle, MD PhD

First Name & Middle Initial & Last Name & Degree

Silvy Lachance, MD

12. IPD Sharing Statement

Plan to Share IPD

Undecided

IPD Sharing Plan Description

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

Learn more about this trial

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

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