Study of Stem Cell Transplant vs. Non-Transplant Therapies in High-Risk Myelofibrosis

Inclusion Criteria: Recruitment Part:

• Documented diagnosis of pre-fibrotic primary myelofibrosis (pre-fibrotic PMF), overtPMF, post-polycythemia MF (PPV-MF) or post-essential thrombocythemia MF (PET-MF)confirmed by bone marrow biopsy
• Have been tested or have results available for phenotypic driver mutations (JAK2/CALR/MPL) and high molecular risk (HMR) mutations using a broad myeloidmalignancies targeted gene panel.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Able to provide informed consent
• Adequate organ function
• Donor search initiated or patient is agreeable to donor search
• Meet the definition/criteria for high-risk myelofibrosis Study Arm Allocation:
• Grade of fibrosis on bone marrow biopsy available according to World HealthOrganization (WHO) criteria
• Results available for phenotypic driver mutations (JAK2/CALR/MPL) and targetedsequencing results using a broad myeloid malignancy panel with a minimal requirementto include results on High molecular risk (HMR) mutations such asASXL1/EZH2/IDH1/IDH2/SRSF2/U2AF1/TP53
• ECOG performance status 0-2
• Adequate organ function
• Information on donor search and donor type available

Exclusion Criteria: Recruitment Part:

• Blasts in peripheral blood or bone marrow ≥10%
• For patients already on ruxolitinib at study entry, and meet the criteria ofruxolitinib failure
• Previous history of transformation to blast phase or acute myeloid leukemia
• Received allogeneic stem cell transplant for myeloproliferative neoplasm
• Presence of an active uncontrolled infection
• Myocardial infarction in the preceding 3 months
• Active hepatitis A, B or C
• Known human immunodeficiency virus (HIV) positive
• History of active malignancy in the previous 2 years, except basal cell carcinoma orsquamous cell carcinoma of skin or stage 0 cervical cancer
• Any psychiatric illness or social circumstances or significant co-morbid conditionsthat will prevent patient from proceeding to allogeneic hematopoietic celltransplantation.
• Pregnant or breastfeeding women Study Arm Allocation:
• Blasts in peripheral blood or bone marrow ≥10%
• Meet the criteria of ruxolitinib failure
• Presence of an active uncontrolled infection
• Myocardial infarction in the preceding 3 months
• Active hepatitis A, B or C
• Known HIV positive
• History of active malignancy in the previous 2 years, except basal cell carcinoma orsquamous cell carcinoma of skin or stage 0 cervical cancer
• Pregnant or breastfeeding women
• Any psychiatric illness or social circumstances or significant co-morbid conditionsthat will prevent patient from proceeding to allogeneic hematopoietic celltransplantation.
• Time between registration and allocation of study arm >24 weeks