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.

Conflict of interest statement

Financial & competing interests disclosure

Support for this research was provided by the NIH/NCI (R35: 1R35CA210084, JF DiPersio) and BioLineRx Ltd Modi'in-Maccabim-Re'ut, Israel. ZD Crees: Employment/Salary: Barnes-Jewish Hospital and Washington University. K Stockerl-Goldstein: Consulting/Advisory Committees: Celgene; Employment/Salary: Washington University. A Vainstein: Employment/Salary: BioLineRx Ltd H Chen: Employment/Salary: BioLineRx Ltd JF DiPersio: Consulting/Advisory Committees: Cellworks, Arch, Rivervest, Bioline, Amphivena, Bluebird Bio, Celgene, Incyte, NeoImmuneTech, Macrogenics; Employment/Salary: Washington University; Ownership Investment: Magenta, WUGEN. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

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.