NCT00524784

Open-Label Study Designed to Evaluate the Safety and Preliminary Efficacy of ApoCell for the Prevention of Acute GvHD

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)

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 12 (estimated)
• Sponsor: Hadassah Medical Organization · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

Bone marrow transplantation (BMT) has revolutionized the treatment of hematopoietic malignancies.Unfortunately, graft versus host disease (GvHD) remains a major toxicity that greatly limits the application and efficacy of BMT.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. 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 GVHD.

Detailed description

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.

Conditions

• Graft Versus Host Disease
• Hematological Malignancies

Interventions

Type	Name	Description
BIOLOGICAL	ApoCell	Three subjects per cohort will be treated with ApoCell according to an escalating schedule of doses starting at a single dose of 35 million apoptotic cells/kg in the first cohort of three subjects. Unless a DLT is experienced by subjects in a given cohort, the dose in the subsequent cohort will be increased by two-fold. The second cohort will receive 70 millions cells/kg, and the third cohort 140 millions cells/kg. The final fourth cohort will receive 210 millions cells/kg.

Timeline

• Start date: 2009-06-01
• Primary completion: 2012-12-01
• Completion: 2016-04-01
• First posted: 2007-09-05
• Last updated: 2015-06-11

Locations

1 site across 1 country: Israel