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

Study Overview
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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.

Official Title
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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

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

Intervention / Treatment
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* Biological: GLIDE


Participation Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: exploratory, open-label
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-hematologic toxicity related to GLIDE post injection | 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 | Disease progression following GLIDE injection | up to 12 months | 
| Incidence and severity of acute and chronic graft versus host disease (GvHD) | 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 | Monitoring of GLIDE product persistence in host | up to 12 months | 
| Non-Relapse mortality (NRM) | Time to deaths without relapse/recurrence | up to 12 months | 
| Relapse-incidence (RI) | Time to relapse | up to 12 months | 
| Overall survival (OS) | Time to death, irrespective of the cause | up to 12 months | 
| Progression-free survival (PFS) | It is time to any of the following: OS, RI, NRM, Time to relapse, Relapse free survival | up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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allogeneic hematopoietic stem cell transplantation, relapsed hematopoietic malignancy, HLA matched donor, minor histocompatibilty antigen (MiHA)