Ensayos clínicos

Inclusion Criteria:

• Documented diagnosis of primary myelofibrosis according to WHO criteria or post PV myelofibrosis or post ET myelofibrosis as per IWG-MRT criteria
• Age 18-70 years
• Intermediate-2/ high-risk disease as per Dynamic IPSS (DIPSS) criteria OR Intermediate-1 risk disease with one of the following additional unfavorable features known to impact the survival adversely
  • Red cell transfusion dependency
  • Unfavorable Karyotype
  • Platelet count <100 x 109/l
• Blasts in the PB and BM <20% prior to study enrollment
• Availability of a suitable matched related (6/6 or 5/6) or unrelated donor (10/10 or 9/10 antigen or allele matched).
• Able to give informed written consent
• ECOG Performance status of 0-2.
• Life expectancy >3 months
• Off all MF-directed therapy including investigational agents for at least 2 weeks prior to study enrollment and recovered from all toxicities*
• Adequate organ function
  • Adequate renal function - creatinine <1.5 x IULN
  • Adequate hepatic function - AST/ALT <2.5 x IULN, Total Bilirubin <1.5 x IULN
  • Adequate hematopoietic function - Platelet ≥50 x 109/l and ANC ≥1.0 x 109/l
  • LVEF >40% (MUGA or echocardiogram) Normal per Institutional standard
  • Adequate pulmonary function with DLCO >50%
    • A patient who has been on stable dose of Ruxolitinib and has received ruxolitinib ≤6 months prior to the study entry will be considered potentially eligible for the study with the caveat that there is no evidence of loss of response (>5cm increase in spleen size from the nadir).

Exclusion Criteria:

• Any previous JAK2 inhibitor treatment prior to study enrollment, with the exception of Ruxolitinib
• Hypersensitivity to JAK inhibitor
• Clinical or laboratory evidence of cirrhosis
• Prior allogeneic transplant for any hematopoietic disorder
• >20% blast in the PB or BM prior to HCT or had leukemic transformation (>20% blasts in PB or BM any time prior to HCT)
• Syngeneic donor
• Cord Blood transplant
• Active uncontrolled infection
• H/o another malignancy within 5-years of date of HCT except h/o basal cell or squamous cell carcinoma of skin or PV or ET
• Known HIV positive
• Pregnancy at the time of BMT
• Any other concurrent illness which in investigator's opinion puts the patient at excessive risk of treatment related toxicities
• Unable to give informed consent
• Active infection with hepatitis A,B or C virus
• Subjects who require therapy with a strong CYP3A4 inhibitor prior to enrollment to this study