Ruxolitinib in Combination With Autotransplant
Myelofibrosis, MF
About this trial
This is an interventional treatment trial for Myelofibrosis focused on measuring Myelofibrosis, RUXOLITINIB, Autologous stem cell transplant
Eligibility Criteria
Inclusion Criteria:
- Histologically documented diagnosis of MF (idiopathic or post PV/ET)
- Age 18-75 years
Intermediate-2/ high-risk disease as per Dynamic IPSS (DIPSS) criteria or Intermediate-1 risk disease with one of the following features within one year from screening:
- Red cell transfusion dependency
- unfavorable Karyotype
- platelet count <100 x 109/L
- symptomatic splenomegaly
- PB blasts > 1%
- Blasts in PB <20% prior to study enrollment
- No available suitable matched related (6/6 or 5/6) or unrelated donor (8/8 or 7/8 allele matched) or unwilling or unable to pursue allogeneic stem cell transplant
- WBC <50,000/ml at screening
- Able to give informed written consent
- ECOG Performance status of 0-2
- Life expectancy >6 months
- Off all myelofibrosis-related investigational or standard agents (except for ruxolitinib) for at least 4 weeks prior to study enrollment and recovered from all toxicities. If patient is already on ruxolitinib for a minimum of 16 weeks prior to study enrollment, patient can proceed to mobilization and collection
Adequate organ function defined as the following (*unless clearly disease related):
- Adequate renal function - creatinine <2 x ULN
- Adequate hepatic function - AST/ALT <3 x ULN, Total Bilirubin <3 x ULN, exception is elevated indirect bilirubin attributed to Gilbert's syndrome or hemolysis
- Adequate hematopoietic function - Platelet ≥50 x 109/L (without transfusion) and ANC ≥1.0 x 109/L
- LVEF >40% (MUGA or echocardiogram)
- Adequate pulmonary function with DLCO >40%
Exclusion Criteria:
- Hypersensitivity to JAK inhibitor
- Clinical evidence of cirrhosis
- Leukemic transformation (>20% blasts in PB or BM any time prior to HCT)
- Platelet count <50 x 109/L
- Active uncontrolled infection
- History of another malignancy within 5-years of date of HCT except history of basal cell or squamous cell carcinoma of skin or PV or ET
- Known HIV positive
- Woman of childbearing potential unwilling or unable to use adequate contraception Pregnant or nursing females Known active infection with hepatitis A, B or C virus
Sites / Locations
Arms of the Study
Arm 1
Experimental
Ruxolitinib / INC 424
Ruxolitinib, Jakafi ®, will be given orally at standard dose daily for 16 weeks pre ASCT and up to 3 months post-ASCT for 10 patients (allowing for 2 additional screen failures). Patients will restart ruxolitinib at 100 days after the ASCT as long as their platelet count is at least 50 x103. For patients whose platelet count is below 50 x103 at day 100, ruxolitinib should be restarted once platelet count reaches 50 x103. The dose of ruxolitinib can be titrated up as per clinical guidelines. PBSC mobilization will include G-CSF 10 mcg/kg/day. HDC for ASCT will consist of IV busulfan 2.0 mg/KBW once daily x 4 for days -5 to -2.