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

Ciusss de L'Est de l'Île de Montréal

Status and phase

Unknown

Phase 2

Phase 1

Conditions

Relapsed CLL

Relapsed Adult AML

Hematologic Cancer

Relapsed Myelodysplastic Syndromes

Relapsed Adult ALL

Relapsed Multiple Myeloma

Relapsed Non Hodgkin Lymphoma

Relapsed Hodgkin's Lymphoma

Relapse Leukemia

Treatments

Biological: GLIDE

Study type

Interventional

Funder types

Other

Identifiers

NCT03091933

CR-MIHA-001

Details and patient eligibility

About

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.

Full 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.

Enrollment

20 estimated patients

Sex

All

Ages

18 to 65 years old

Volunteers

No 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.