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

Relapsed Multiple Myeloma Clinical Trial

— GLIDE  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03091933
• Other study ID #: CR-MIHA-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: March 21, 2017
• Last updated: December 4, 2017
• Start date: February 6, 2017
• Est. completion date: March 31, 2019

Study information

• Verified date: December 2017
• Source: Ciusss de L'Est de l'Île de Montréal
• Contact: Jean-Guy Némorin, PhD
• Phone: (514) 252-3400
• Email: jgnemorin[@]centrec3i.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: March 31, 2019
• Est. primary completion date: March 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hematologic Cancer
• Hematologic Neoplasms
• Hodgkin Disease
• Lymphoma
• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Myelodysplastic Syndromes
• Neoplasms
• Preleukemia
• Recurrence
• Relapse Leukemia
• Relapsed Adult ALL
• Relapsed Adult AML
• Relapsed CLL
• Relapsed Hodgkin's Lymphoma
• Relapsed Multiple Myeloma
• Relapsed Myelodysplastic Syndromes
• Relapsed Non Hodgkin Lymphoma

Intervention

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

Locations

Country	Name	City	State
Canada	CIUSSS d l'Est-de-l'Île-de-Montréal	Montreal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Ciusss de L'Est de l'Île de Montréal

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Non-hematologic toxicity related to GLIDE post injection	No death or other toxic events directly related to GLIDE injection	6 months
Secondary	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
Secondary	Incidence and severity of acute and chronic graft versus host disease (GvHD)	Progression (if any) or induction of GvHD	up to 12 months
Secondary	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
Secondary	Non-Relapse mortality (NRM)	Time to deaths without relapse/recurrence	up to 12 months
Secondary	Relapse-incidence (RI)	Time to relapse	up to 12 months
Secondary	Overall survival (OS)	Time to death, irrespective of the cause	up to 12 months
Secondary	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