Summary

This phase II trial studies the side effects and how well CXCR4 antagonist BL-8040 works in mobilizing stem cells for donor transplant in healthy donors and patients with hematological malignancies that have spread to other places in the body and usually cannot be cured or controlled with treatment. CXCR4 antagonist BL-8040 may help donors produce enough stem cells from the bone marrow into blood after one dose compared to other drugs used for the same purpose, which require multiple doses.

Objectives

PRIMARY OBJECTIVES:
I. To assess the efficacy of a single injection of CXCR4 antagonist BL-8040 (BL-8040) to mobilize >= 2 x 10^6 CD34+ cells/kg of recipient weight after no more than two leukapheresis collections from healthy donors.

SECONDARY OBJECTIVES:
I. To assess the safety and tolerability of BL-8040 in healthy donors.
II. To assess the kinetics of neutrophil and platelet recovery post-transplant in patients undergoing allogeneic stem cell transplant.
III. To determine the incidence of primary and secondary graft failure up to one year after transplantation of hematopoietic cells mobilized with BL-8040.
IV. To determine the incidence of grade 2-4 acute graft versus host disease (GvHD) in patients who have undergone transplantation of hematopoietic cells mobilized with BL-8040.
V. To determine the incidence of chronic GvHD at 1 year in patients who have undergone transplantation of hematopoietic cells mobilized with BL-8040.
VI. To determine the proportion of subjects who collect 5 x 10^6 CD34+ cells/kg of recipient weight in a single leukapheresis and in 2 leukapheresis sessions.
VII. To determine the incidence of cytomegalovirus (CMV) reactivation after transplantation of hematopoietic cells mobilized with BL-8040 in CMV seropositive recipients.
VIII. To determine the incidence of treatment-related mortality and disease relapse/progression after transplantation of hematopoietic cells mobilized with BL-8040.
IX. To determine the probability of event free and overall survival after transplantation of hematopoietic cells mobilized with BL-8040.
X. To determine the change in peripheral blood CD34+ cells concentration from baseline throughout day 1 and day 2 (if a second leukapheresis is required).
XI. To assess the pharmacokinetic profile of BL-8040.

TERTIARY OBJECTIVES:
I. To measure alterations in CXCR4 expression and receptor occupancy in the peripheral blood of healthy donors following treatment with BL-8040.
II. To determine the kinetics of mobilization of CD34+ cells and characterize CD34+ subsets mobilized by BL-8040.
III. To characterize the cellular composition of the hematopoietic stem progenitor cell (HSPC) graft including T-cell subpopulations in peripheral blood and in the stem cell product.

OUTLINE:
DONOR MOBILIZATION: Donors receive CXCR4 antagonist BL-8040 subcutaneously (SC) on day 1 and undergo leukapheresis over 180-270 minutes after the injection per institutional protocol. If the donor does not reach the collection goal for mobilization, donors undergo a second leukapheresis on day 2.

STEM CELL TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant (PBSCT) on day 0.

After completion of study treatment, donors are followed up at 7 and 30 days and then annually for 5 years and recipients for 12 months.