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Hematologic malignancies often require hematopoietic cell transplantation (HCT). Randomized trials demonstrated the advantages of hematopoietic stem/progenitor cells (HSPC) mobilized from the peripheral blood (PB) compared to bone marrow (BM) for HCT. The most commonly used mobilization regimen utilize G?CSF (-/+ Plerixafor), which requires 4-5 treatment days and often involves several apheresis sessions. In addition, the graft composition; CD34+, mesenchymal stem cells (MSCs), NK and T cell subsets may influence recipient outcomes in terms of engraftment, anti-tumor activity, GVHD, morbidity and mortality.

BL-8040 (BKT140) is a novel CXCR4 antagonist that binds the receptor with high affinity and long receptor occupancy. Studies in mice demonstrated that single BL-8040 injection mobilized long term repopulating cells sufficient for transplantation.  Results from a study in multiple myeloma patients showed that BL-8040 when combined with G-CSF enabled the collection of high number of CD34+ cells in a single aphaeresis procedure. The potential of BL-8040 monotherapy as a mobilizing agent and its derived graft composition and quality is currently evaluated in a phase I clinical study in healthy volunteers (NCT02073019). 

The first part of the study was randomized, double-blind, placebo-controlled dose escalation. Each cohort included 8 subjects in a 6+2 design (0.5, 0.75 and 1 mg/kg). After obtaining informed consent, BL-8040 was administered SC QD on 2 consecutive days. Frequent PB samples were tested for the number of WBC, CD34+, B, T, and NK cells, MSC, MSC colony forming cells and HPCs colony forming cells. In the second part, 8 subjects are receiving single injection of BL-8040 (1mg/kg) and 4 hours later undergo a standard leukapheresis (18 L) procedure. The composition of the collected graft is being tested for the number of CD34+ cells per kg, number and type of MSCs per kg, number and type of T, B, NK and dendritic cells. 

BL-8040 was found safe and well tolerated at all doses tested (0.5-1 mg/kg). The primary treatment related AEs were mild to moderate transient injection site and systemic reactions. BL-8040 triggered substantial mobilization of WBC to the circulation. The mean WBC count, of all patients receiving BL-8040, rose from a baseline of 6.3 to 29.7 X 10⁹/L at 4 hr post dose. Dramatic mobilization of HSPC (CD34+ cells) was observed across all doses tested. Mean CD34+ count at baseline was 5.8/µL; four hours post dose, the count rose to a mean of 8, 37, 31 and 35 cells/µL and four hours post the second dose of BL-8040, it further increased to 9, 38, 46 and 58 cells/µL (placebo, 0.5, 0.75 and 1 mg/kg, respectively). BL-8040 administration resulted in rapid mobilization of MSC and HPC colony forming, T, B and NK cells. Preliminary results from the second part of the study indicate the potential to collect sufficient amount of CD34+ cells following single apheresis session. Long receptor occupancy and long pharmacodynamic effect (≥24 hours post dosing) were also observed.