About this trial
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.
Eligibility criteria
Qualifiers
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
Disqualifiers
PART 1 JAK INHIBITOR ADMINISTRATION: Contraindication to receiving ruxolitinib including patients who have known hypersensitivity to JAK inhibitors and excipients
PART 1 JAK INHIBITOR ADMINISTRATION: History of prior allogeneic transplant
PART 1 JAK INHIBITOR ADMINISTRATION: Leukemic transformation (> 20% blasts)
PART 1 JAK INHIBITOR ADMINISTRATION: Uncontrolled viral, bacterial, or fungal infection despite being on therapy
Trial design
Treatments tested in this trial
- Ruxolitinib
- Allogeneic Hematopoietic Stem Cell Transplantation
- Busulfan
- Computed Tomography
- Cyclophosphamide
- Echocardiography Test
- Fludarabine
- JAK Inhibitor
- Melphalan
- Methotrexate
- Tacrolimus
- Biospecimen Collection
- Bone Marrow Aspiration
- Bone Marrow Biopsy
Treatment groups
Sponsors and collaborators
Fred Hutchinson Cancer Center
Lead sponsor
Incyte Corporation
Collaborator