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

Participation Requirements

• Sex:

  ALL

• Eligible Ages:

  18 to 70

Participation Criteria

Inclusion Criteria:

Recruitment Part:

* Documented diagnosis of pre-fibrotic primary myelofibrosis (pre-fibrotic PMF), overt PMF, 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 myeloid malignancies 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 Health Organization (WHO) criteria
* Results available for phenotypic driver mutations (JAK2/CALR/MPL) and targeted sequencing results using a broad myeloid malignancy panel with a minimal requirement to include results on High molecular risk (HMR) mutations such as ASXL1/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 of ruxolitinib 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 or squamous cell carcinoma of skin or stage 0 cervical cancer
* Any psychiatric illness or social circumstances or significant co-morbid conditions that will prevent patient from proceeding to allogeneic hematopoietic cell transplantation.
* 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 or squamous cell carcinoma of skin or stage 0 cervical cancer
* Pregnant or breastfeeding women
* Any psychiatric illness or social circumstances or significant co-morbid conditions that will prevent patient from proceeding to allogeneic hematopoietic cell transplantation.
* Time between registration and allocation of study arm \>24 weeks