BioLineRx Ltd. has announced that it has commenced a Phase 1/2 trial for BL-8040, in combination with standard of care immunosuppressive therapy, as a novel treatment for two bone marrow failure conditions: hypoplastic myelodysplastic syndrome (hMDS) and aplastic anemia (AA).
The open-label trial, conducted in collaboration with MD Anderson Cancer Center in Houston, will examine BL-8040’s ability to improve bone marrow cellularity and peripheral blood counts in up to 25 patients suffering from these bone marrow failure conditions.
The study’s primary endpoint is to evaluate the safety and tolerability of treatment with BL-8040 on top of the standard immunosuppressive regimen of Anti-Thymocyte Globulin (hATG), Cyclosporine and Methylprednisolone (steroids) in hMDS and AA patients. Secondary endpoints include assessment of the clinical efficacy (response rate), time and duration of response to the treatment, and overall survival following treatment.
Safety and efficacy will be assessed at defined time points throughout the study. Duration of response and overall survival will also be assessed as part of the study’s long term follow up protocol.
Study patients will initially receive BL-8040 as a monotherapy for ten days. From Day 11 through Day 14, patients will receive hATG, Methylprednisolone and Cyclosporine. Subsequently, during the first month of treatment, from Day 15 until Day 30, patients will continue treatment only with Methylprednisolone and Cyclosporine.
Beginning in the second month, patients will continue daily treatments with Cyclosporine through the end of the sixth month, which is the end of the study treatment. In addition, beginning in the second month, BL-8040 will be administered daily as part of the maintenance period for the first 5 days of each month, also until the end of the six-month study period.
Both hMDS and AA are characterized by a T cell-driven autoimmune attack on the bone marrow that results in depletion of hematopoietic precursors, leading to anemia and low white blood cell counts. In this regard, high CXCR4 expression on pathogenic T cells has been suggested to facilitate infiltration to the bone marrow. BL-8040, a CXCR4 antagonist, is expected to inhibit migration of pathogenic T cells to the bone marrow, thereby mitigating the severe depletion of hematopoietic stem and progenitor cells.
In addition, BL-8040 may directly affect the number of hematopoietic precursors. Preclinical studies in mice showed that multiple doses of BL-8040 led to a marked increase in the number of hematopoietic progenitor cells and hematopoietic stem cells in both the bone marrow and peripheral blood. BL-8040 also promoted production of megakaryocytes in the bone marrow, leading to a prolonged increased platelet production. These direct effects of BL-8040, along with the exclusion of the pathogenic T cells from the bone marrow, may improve bone marrow cellularity and peripheral blood counts.
Dr. Kinneret Savitsky, CEO of BioLineRx, stated, “We are very pleased to commence an additional clinical trial for BL-8040, our unique oncology platform, in these two orphan designations that represent significant unmet medical needs. This study expands our existing successful collaboration with the MD Anderson Cancer Center, where we are already running a Phase 2 trial in relapsed/refractory AML. The hMDS/AA trial will assess BL-8040 in combination with standard of care immunosuppressive therapy, with interim results expected by the end of 2016. We are very hopeful that BL-8040, as part of a novel treatment regimen, will significantly improve bone marrow cellularity and peripheral blood counts in patients suffering from these difficult bone marrow failure conditions.”