GENESIS: Phase III trial evaluating BL-8040 + G-CSF to mobilize hematopoietic cells for autologous transplant in myeloma

Abstract

Effective hematopoietic cell transplantation relies upon collecting adequate numbers of CD34⁺ hematopoietic stem cells, typically from peripheral blood. A minimum of ≥2 × 10⁶ CD34⁺ cells/kg are necessary, while transplants of ≥5-6 × 10⁶ CD34⁺ cells/kg are associated with improved hematopoietic recovery. Granulocyte colony stimulating factor (G-CSF) remains the gold standard for hematopoietic stem cell mobilization. However, in randomized trials for autologous-hematopoietic cell transplantation in multiple myeloma, approximately 45% of patients remain unable to optimally mobilize with G-CSF alone despite multiple injections and apheresis days. Therefore, reducing mobilization failures remains an unmet need. The study objective is to evaluate the superiority of one dose of BL-8040 plus G-CSF over placebo plus G-CSF to mobilize ≥6.0 × 10⁶ CD34⁺ cells/kg in up to two apheresis days. ClinicalTrials.gov: NCT03246529.

Keywords: CXCR4/SDF-1 signaling; apheresis; autologous hematopoietic cell transplantation; multiple myeloma; stem cell mobilization.

Figure 1.. Mobilization protocol.

The mobilization protocol begins once patients complete all screening requirements and meet study eligibility criteria. On mobilization Days 1–5, patients receive a single subcutaneous dose of G-CSF each AM (*and Days 6–8 in AM if needed). On Day 4, patients receive a single subcutaneous dose of BL-8040 or placebo in the PM (*and Day 6 in PM if needed). On Day 5, the patient proceeds with apheresis. If the patient does not collect ≥6.0 × 10⁶ CD34⁺ cells/kg after the first apheresis on Day 5, they will proceed with apheresis on Day 6. If the patient does not mobilize to goal, they may receive a second dose of BL-8040 or placebo on the evening of Day 6 and proceed to apheresis Day 7 and Day 8 as needed to collect to goal. G-CSF: Granulocyte colony stimulating factor.