Clinical trial NCT03091933: Antiminor Histocompatibility Complex (MiHA) T Cells for Patients With Relapsed Hematologic Malignancies Following Matched HSCT (Guided Lymphocyte Immunopeptide Derived Expansion)
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
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: 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)
Lead sponsor: Ciusss de L'Est de l'Île de Montréal
Sponsor class: OTHER
First posted: 2017-03-27
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: exploratory, open-label
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Non-hematologic toxicity related to GLIDE post injection
timeFrame: 6 months
Secondary outcomes:
measure: Response of hematologic malignancy (acute leukemia (ALL, AML, biphenotypic), CLL, HL, NHL, MM or MDS) post-injection
timeFrame: up to 12 months
measure: Incidence and severity of acute and chronic graft versus host disease (GvHD)
timeFrame: up to 12 months
measure: Persistence of GLIDE in the host and homing to peripheral blood, bone marrow and other tissues
timeFrame: up to 12 months
measure: Non-Relapse mortality (NRM)
timeFrame: up to 12 months
measure: Relapse-incidence (RI)
timeFrame: up to 12 months
measure: Overall survival (OS)
timeFrame: up to 12 months
measure: Progression-free survival (PFS)
timeFrame: up to 12 months
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: CIUSSS d l'Est-de-l'Île-de-Montréal
state: Quebec
Study officials:
affiliation: CIUSSS d l'Est-de-l'Île-de-Montréal
name: Denis-Claude Roy, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: CIUSSS d l'Est-de-l'Île-de-Montréal
name: Jean-Sébastien Delisle, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: CIUSSS d l'Est-de-l'Île-de-Montréal
name: Silvy Lachance, MD
role: PRINCIPAL_INVESTIGATOR
References: