Peri-Hematopoietic Cell Transplantation Ruxolitinib in Patients With Myelofibrosis and Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes
Fred Hutchinson Cancer Center
Summary
This phase II trial tests the effect of adding ruxolitinib to standard graft versus host disease (GVHD) prevention in treating older patients with myelofibrosis (MF) or myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap syndromes before, during, and after a donor (allogeneic) hematopoietic cell transplant (HCT). Allogeneic HCT is a procedure in which a person receives blood-forming stem cells (cells from which all blood cells develop) from a genetically similar, but not identical donor. Giving chemotherapy, such as cytoxan and busulfan or fludarabine and melphalan, before a donor transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. However, sometimes the transplanted cells from a donor can attack the body's normal cells (called GVHD). Giving standard prevention (prophylaxis) therapies, such as tacrolimus and methotrexate, after the transplant may stop this from happening. Methotrexate, a type of antifolate, is in a class of medications called antimetabolites. Methotrexate stops cells from using folic acid to make deoxyribonucleic acid and may kill cancer cells. Tacrolimus is used to help reduce the risk of rejection by the body of organ and bone marrow transplants. Ruxolitinib, a type of Janus-associated kinase (JAK) inhibitor, blocks a protein called JAK, which may help keep abnormal blood cells or cancer cells from growing. It may also lower the body's immune response and prevent the development of GVHD. Giving ruxolitinib before, during and after allogeneic HCT in addition to standard GVHD prophylaxis may be safe, tolerable and effective in preventing GVHD and improving outcomes in older patients with MF or MDS/MPN overlap syndrome.
Description
OUTLINE: PART 1: Patients receive ruxolitinib or an alternate JAK-inhibitor for at least 8 weeks prior to the start of HCT conditioning. Starting on day -4, patients receive 5 mg of ruxolitinib orally (PO) twice daily (BID) for 12 months then PO once daily (QD) until 18 months. Patients receive high intensity conditioning with cyclophosphamide intravenously (IV) on days -7 and -6 and busulfan IV over 3 hours on days -5 to -2 or reduced intensity conditioning with fludarabine IV over 30 minutes on days -6 to -2 and melphalan IV over 15-30 minutes on days -3 and -2. PART 2: Patients receive st…
Eligibility
- Age range
- 18–75 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * PART 1 JAK INHIBITOR ADMINISTRATION: Age 18-75 years * Patients \> 75 must be considered an HCT candidate, meet all protocol criteria and have comorbidity score =\< 3 and Karnofsky performance status (KPS) \> or = to 90. Patients. \> 75 who do not meet these criteria may be presented at PCC for consensus exception * PART 1 JAK INHIBITOR ADMINISTRATION: Disease criteria * Diagnosis of primary or secondary MF as defined by the 2022 World Health Organization classification system or the International Consensus Classification for Myeloid and Acute Leukemias * Diagnos…
Interventions
- DrugRuxolitinib
Given PO
- ProcedureAllogeneic Hematopoietic Stem Cell Transplantation
Given infusion
- DrugBusulfan
Given IV
- ProcedureComputed Tomography
Undergo CT
- DrugCyclophosphamide
Given IV
- ProcedureEchocardiography Test
Undergo echocardiography
- DrugFludarabine
Given IV
Location
- Fred Hutch/University of Washington Cancer ConsortiumSeattle, Washington