This phase II trial studies how well ruxolitinib phosphate before and after stem cell transplant works in treating patients with primary or secondary myelofibrosis. Ruxolitinib phosphate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fludarabine and melphalan, 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. Giving chemotherapy before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and 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. The donated stem cells may also replace the patient’s immune cells and help destroy any remaining cancer cells.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03427866.
PRIMARY OBJECTIVE:
I. Graft versus host disease (GVHD) free and relapse free survival at 1 year (GRFS) as defined as grades III-IV acute GVHD-free/chronic GVHD requiring systemic immunosuppression-free/disease relapse-free survival at 1 year after hematopoietic stem cell transplantation (HCT).
SECONDARY OBJECTIVES:
I. 1-year and 2-year progression free survival (PFS).
II. 1-year and 2-year overall survival (OS).
III. Cumulative incidence of grades II-IV and III-IV acute GVHD at 6 months after HCT.
IV. Cumulative incidence of moderate to severe chronic GVHD at 12 and 24 months after HCT.
V. Cumulative incidence of non-relapse mortality (NRM) at 6, 12 and 24 months.
VI. Rate of engraftment.
VII. Median time on ruxolitinib phosphate (ruxolitinib) after HCT as a measure of feasibility.
VIII. Toxicity as measured by Common Terminology Criteria for Adverse Events (CTCAE) grade 3-4 adverse events as a measure of safety of ruxolitinib after in patients with myelofibrosis.
IX. To characterize immunological reconstitution, changes in cytokines as they relate to GVHD in the setting of ruxolitinib administration.
X. To characterize the relationship between JAK-STAT signaling with PD-L1 expression and with disease response to therapy.
OUTLINE:
Starting 1 week prior to the initiation of conditioning, patients receive ruxolitinib phosphate orally (PO) twice daily (BID). Patients continue to receive ruxolitinib phosphate during conditioning and during and after HCT. Treatment repeats every 28 days for up to 13 cycles (12 months after HCT) in the absence of disease progression or unacceptable toxicity.
CONDITIONING: Patients receive fludarabine intravenously (IV) over 30 minutes on days -7 to -3 and melphalan IV over 60 minutes on day -2.
TRANSPLANT: Patients undergo HCT on day 0.
After completion of study treatment, patients are followed up at 30 days and then every 6 months for up to 2 years.
Lead OrganizationDana-Farber Harvard Cancer Center
Principal InvestigatorGabriela Soriano Hobbs
