This pilot early phase I trial studies how well fludarabine phosphate, busulfan, rabbit anti-thymocyte globulin, tacrolimus, and methotrexate work in treating participants with blood cancer undergoing stem cell transplant. Drugs used in chemotherapy, such as fludarabine phosphate, busulfan, and methotrexate, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Rabbit anti-thymocyte globulin and tacrolimus may be an effective treatment for lowering the incidence of graft-versus-host disease caused by a transplant. Giving fludarabine phosphate, busulfan, rabbit anti-thymocyte globulin, tacrolimus, and methotrexate may work better in treating participants with blood cancer.
Additional locations may be listed on ClinicalTrials.gov for NCT02916979.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVES:
I. To define the 100 day survival of patients being treated on this regimen.
SECONDARY OBJECTIVES:
I. To define clinical endpoints using this myeloablative allogeneic transplant regimen.
II. Time to marrow engraftment (defined as absolute neutrophil count > 500/mm^3 and platelets > 20,000/mcl for three consecutive days (count first day as engraftment).
III. Response to treatment at 100 days.
IV. Response to treatment at one year.
V. One year survival.
VI. Treatment-related mortality in the first 100 days.
VII. Toxicities associated with this treatment regimen.
VIII. Incidence of acute and chronic graft versus host disease (GVHD).
IX. Donor-recipient chimerism following transplant at days 30, 60 and 90.
X. To characterize the incidence, prevalence and function of myeloid-derived suppressor cells (MDSCs) and immune checkpoint regulators (VISTA, CTLA-4, PD-L1) during early immune recovery following an allogeneic stem cell transplant.
XI. Define the MDSCs frequency and checkpoint regulator expression on MDSCs, peripheral blood mononuclear cells and myeloid subsets.
OUTLINE:
Participants receive fludarabine phosphate intravenously (IV) over 30 minutes daily on days -7 to -3, busulfan IV over 3-4 hours daily on days -6 to -3, and rabbit anti-thymocyte globulin (ATG) IV over 10-12 hours on days -6 and -5. Beginning day -2, participants receive tacrolimus orally (PO) every 12 hours with taper between 90-120 days and stop by days 150-180. Participants undergo standard of care transplant on day 0. Participants then receive methotrexate on days 1, 3, and 6 or 1, 3, 6, and 11. Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants are followed up periodically.
Lead OrganizationDartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Principal InvestigatorKenneth R. Meehan
