This phase II trial studies how well adding ruxolitinib phosphate before a reduced intensity donor stem cell transplant works in treating patients with myelofibrosis. Ruxolitinib phosphate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving ruxolitinib phosphate and chemotherapy before a donor stem cell may help stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT01790295.
PRIMARY OBJECTIVES:
I. To determine the feasibility of combining ruxolitinib (ruxolitinib phosphate) (INC424) with a reduced intensity conditioning (RIC) regimen likely to produce success post transplantation, success being defined as patient being alive, and without graft failure at day 100-post allogeneic stem cell transplantation in patients who receive (a) related donor transplant and in those who receive (b) an unrelated donor transplant.
SECONDARY OBJECTIVES:
I. Neutrophil and platelet recovery.
II. Non-relapse mortality (NRM) at 100 days and 1-year.
III. Acute and chronic graft versus host disease (GvHD) at 1-year.
IV. Chimerism studies at 30, 60 and 100 days post-transplant.
V. Remission status according to International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria at day 100, and 6 and 12 months post-transplant.
VI. Relapse/progression (defined as per IWG-MRT criteria) at 1-year post-transplant.
VII. Progression-free survival at 1-year.
VIII. Overall survival at 1-year.
IX. Impact of allogeneic stem cell transplant on myelofibrosis associated symptoms and overall quality of life.
X. Expression profiling and measurements of cytokines prior to start of ruxolitinib, prior to start of chemotherapy for conditioning, day +30 and day +100 post-transplant.
XI. Association of cytokines levels with acute and chronic GvHD.
OUTLINE:
RUXOLITINIB PHOSPHATE: Patients receive ruxolitinib phosphate orally (PO) twice daily (BID) on days -67 to -8, with taper beginning on day -11.
CONDITIONING THERAPY: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes once daily (QD) and busulfan IV over 2 hours QD on days -5 to -2.
TRANSPLANT: Patients undergo allogeneic bone marrow or peripheral blood stem cell (PBSC) transplant on day 0.
GVHD PROPHYLAXIS: Patients receive cyclosporine or tacrolimus IV or PO BID on days -2 to 180 and methotrexate IV on days 1, 3, and 6. Patients undergoing donor or mismatched related donor transplant also receive anti-thymocyte globulin on days -3 to -1.
After completion of study treatment, patients are followed up at 30, 60, and 100 days, 6 months, 1 year, 18 months, 2 years, 3, years, and 4 years.
Lead OrganizationMount Sinai Hospital
Principal InvestigatorJohn Omar Mascarenhas
