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

NCT ID: NCT03091933

Last Updated: 2017-12-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-02-06

Study Completion Date

2019-03-31

Brief Summary

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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

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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.

Conditions

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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

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

exploratory, open-label
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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GLIDE

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

Group Type EXPERIMENTAL

GLIDE

Intervention Type BIOLOGICAL

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

Interventions

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GLIDE

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

Intervention Type BIOLOGICAL

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ciusss de L'Est de l'Île de Montréal

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Denis-Claude Roy, MD PhD

Role: PRINCIPAL_INVESTIGATOR

CIUSSS d l'Est-de-l'Île-de-Montréal

Jean-Sébastien Delisle, MD PhD

Role: PRINCIPAL_INVESTIGATOR

CIUSSS d l'Est-de-l'Île-de-Montréal

Silvy Lachance, MD

Role: PRINCIPAL_INVESTIGATOR

CIUSSS d l'Est-de-l'Île-de-Montréal

Locations

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CIUSSS d l'Est-de-l'Île-de-Montréal

Montreal, Quebec, Canada

Site Status RECRUITING

Countries

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Canada

Central Contacts

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Jean-Guy Némorin, PhD

Role: CONTACT

Phone: (514) 252-3400

Email: [email protected]

Stéphanie Thiant, PhD

Role: CONTACT

Phone: (514) 252-3400

Email: [email protected]

Facility Contacts

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Jean-Guy Némorin, PhD

Role: primary

Stéphanie Thiant, PhD

Role: backup

Other Identifiers

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CR-MIHA-001

Identifier Type: -

Identifier Source: org_study_id