Phase 1/2a, Multicenter, Open-Label Study Designed to Evaluate the Safety, Tolerability and Preliminary Efficacy of ApoCell Administration, a Donor Apoptotic Cell-Based Product, for the Prevention of Acute Graft Versus Host Disease (GvHD) in Subjects With Hematologic Malignancies Undergoing Allogeneic Sibling HLA-Matched Hematopoietic Stem Cell Transplantation (HSCT)
Allogeneic hematopoietic stem-cell transplantation (HSCT) has revolutionized the treatment
of hematopoietic malignancies, inherited hematopoietic disorders, aplastic anemia, and other
severe diseases. Unfortunately, graft versus host disease (GvHD) remains a major toxicity
that greatly limits the application and efficacy of allogeneic HSCT, occurring commonly
after the procedure and affecting 30 to 80% of patients. Acute GvHD occurs within 100 days
in up to 50% of allogeneic HLA-matched HSCT recipients despite prophylactic
immunosuppressive drugs.
The most efficient treatment for GvHD prevention is T cell depletion. However, most
clinicians avoid that modality due to the crucial effect of T cells in prevention of tumor
relapse. Current standard prophylaxis and therapy for acute GvHD include mainly the use of
immunosuppressive drugs that help less than 50% of the patients and are associated with
increased infection risk. New strategies of GvHD prophylaxis are examined and this study
uses a physiological strategy of antigen presenting cell (APC) tolerance induction that will
modulate effector cells either directly or via T regulatory cells.
ApoCell treatment is anticipated to be a prophylactic measure for acute GvHD by inducing
tolerance in the donor effector cells, leading to a potentially significant decrease in the
immune response of the donor cells against the recipient. The effects of apoptotic cells on
preventing GvHD may involve the following mechanisms: inhibit pro-inflammatory cytokine
production, promote anti-inflammatory cytokines production, induce tolarogenic APCs,
decrease ability to stimulate T-cell responses, delete CD8 T-effector cells, induce
regulatory T-cells, and inhibit response to inflammatory cytokines and LPS.
Tolarex Ltd. is proposing a novel cell-based approach of donor apoptotic cells treatment,
ApoCell, for a Phase I-IIa study of patients undergoing sibling HSCT with high risk of
developing acute GvHD. The ApoCell product is composed of HLA-matched donor mononuclear
enriched leukocytes in the form of liquid suspension that will be injected intravenously to
the patient 24 hours prior to HSCT. The ApoCell suspension contains at least 55% of early
apoptotic cells. The cell suspension is prepared under cGMP conditions with PBS solution
within 8 hours prior to intravenous injection and should be stored at 2-8oC until
administered.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
Determine the safety profile and tolerability [dose limiting toxicity (DLT)] of ascending doses of ApoCell in subjects undergoing allogeneic sibling HLA-matched HSCT within 180 days post-transplantation.
180 days
Yes
Reuven Or, Professor
Principal Investigator
Hadassah Medical Organization
Israel: Ethics Commission
TLX-APO-101IL-HMO-CTIL
NCT00524784
June 2009
June 2012
Name | Location |
---|