Ruxolitinib Pre-, During- and Post-HSCT for Patients With Primary or Secondary Myelofibrosis.

• Status: Recruiting
• Trial end date: 2021-09-30
• Target enrollment: 0
• Participant gender: All

Summary

This research study is studying a drug called Ruxolitinib as a possible treatment for Myelofibrosis.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Massachusetts General Hospital
• Collaborator: Incyte Corporation

Criteria

Inclusion Criteria:

• Participants must have pathologically confirmed primary myelofibrosis according to WHO criteria1 or secondary myelofibrosis as defined by the IWG-MRT criteria.19

• Intermediate-2/ high-risk disease as per Dynamic IPSS (DIPSS) criteria2 (Appendix 1) OR

• Intermediate-1 risk disease with one of the following additional unfavorable features known to impact the survival adversely

• Red cell transfusion dependency2

• Unfavorable Karyotype2

• Platelet count ≤100 x 109/L

• Age 18-75

• Participants must be designated to undergo reduced intensity allogeneic peripheral blood (PB) or bone marrow (BM) hematopoietic stem cell transplantation. Consent will be obtained prior to admission for HCT.

• Participants who will undergo HCT from the following donor types are eligible:

• 5/6 or 6/6 (HLA-A, B, DR) matched related donor

• 7/8 or 8/8 (HLA-A, B, DR, C) matched unrelated donor. Matching in the unrelated setting must be at the allele level

• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)

• Life expectancy of greater than 3 months

• Able to give informed consent

• Off all MF-directed therapy at the time of enrollment, with the exception of ruxolitinib

• Additional Criteria for Cohort 1 Only:

• Patients are candidates for enrollment in cohort 1 if they have an indication for ruxolitinib based on splenomegaly or symptoms and are either on ruxolitinib already or going to start therapy with ruxolitinib.

• Patients that are on ruxolitinib may enroll in study as long as they are willing to remain on ruxolitinib during the study and have not lost response to ruxolitinib defined as an increase in >5 cm in spleen size from nadir. There is no minimum or maximum time requirement for time on ruxolitinib.

• Participants must have splenomegaly (defined by ultrasound or CT scan of the abdomen) or symptoms (demonstrated by the presence of 1 symptom score >5 or 2 symptom scores >3) related to myelofibrosis as measured by the myeloproliferative neoplasm symptom assessment form MPN-SAF (see Appendix F) and platelets >25/μL and hemoglobin >7/dL

• Additional Criteria Cohort 2 Only:

• Participants are ineligible for ruxolitinib - do not have splenomegaly or symptoms of myelofibrosis as defined by the MPN-SAF.

Or

• Participants failed ruxolitinib as defined by loss of response to therapy and

• No allergy to ruxolitinib in the past

Exclusion Criteria:

• Hypersensitivity to any JAK inhibitor

• Prior allogeneic transplant for any hematopoietic disorder

• Had accelerated phase or leukemic transformation (≥10% blasts in PB or BM any time prior to HCT)

• Active uncontrolled infection

• History of another malignancy within 5-years of date of except h/o basal cell or squamous cell carcinoma of skin or Polycythemia Vera or Essential Thrombocythemia

• Patients without normal organ function defined as follows:

• AST (SGOT), ALT (SGPT) and Alkaline Phosphatase ≥ 3 × institutional Upper Limit of Normal (ULN)

• Direct bilirubin >2.0 mg/dL

• Adequate renal function as defined by calculated creatinine clearance≤60 mL/min (Cockcroft-Gault formula)

• Have a chronic or active infection that requires systemic antibiotics, antifungal or antiviral treatment

• Have current or a history of congestive heart failure New York Heart Association (NYHA) class 3 or 4, or any history of documented diastolic or systolic dysfunction (LVEF < 40%, as measured by MUGA scan or echocardiogram)

• Pregnancy at the time of enrollment

• Unable to give informed consent

• Have an uncontrolled intercurrent illness including, but not limited to, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• Subjects who require therapy with a strong CYP3A4 inhibitor prior to enrollment to this study

• Not able to take oral medication