Hematologic Cancer, Relapsed Adult ALL, Relapsed Adult AML, Relapsed CLL, Relapsed Hodgkin's Lymphoma, Relapsed Multiple Myeloma, Relapsed Myelodysplastic Syndromes, Relapsed Non Hodgkin Lymphoma, Relapse Leukemia
Conditions
Keywords
allogeneic hematopoietic stem cell transplantation, relapsed hematopoietic malignancy, HLA matched donor, minor histocompatibilty antigen (MiHA)
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.
Interventions
BIOLOGICALGLIDE
Gudide Lymphocyte by Immunopeptide Derived Expansion (GLIDE) is an anti- Minor histocompatibility (MiHA) cell line
Sponsors
Ciusss de L'Est de l'Île de Montréal
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
exploratory, open-label
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Non-hematologic toxicity related to GLIDE post injection | 6 months | No death or other toxic events directly related to GLIDE injection |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of acute and chronic graft versus host disease (GvHD) | up to 12 months | Progression (if any) or induction of GvHD |
| Persistence of GLIDE in the host and homing to peripheral blood, bone marrow and other tissues | up to 12 months | Monitoring of GLIDE product persistence in host |
| Non-Relapse mortality (NRM) | up to 12 months | Time to deaths without relapse/recurrence |
| Response of hematologic malignancy (acute leukemia (ALL, AML, biphenotypic), CLL, HL, NHL, MM or MDS) post-injection | up to 12 months | Disease progression following GLIDE injection |
| Overall survival (OS) | up to 12 months | Time to death, irrespective of the cause |
| Progression-free survival (PFS) | up to 12 months | It is time to any of the following: OS, RI, NRM, Time to relapse, Relapse free survival |
| Relapse-incidence (RI) | up to 12 months | Time to relapse |
Countries
Canada
Contacts
Primary ContactJean-Guy Némorin, PhD
Backup ContactStéphanie Thiant, PhD
Outcome results
None listed