This phase II trial studies how well giving a JAK inhibitor before a donor stem cell transplant works in treating patients with myelofibrosis that developed without another condition (primary) or evolved from other bone marrow disorders (secondary). JAK inhibitors are a class of drugs that may stop the growth of abnormal cells by blocking an enzyme needed for cell growth. Giving a JAK inhibitor such as ruxolitinib before a donor stem cell transplant may help reduce symptoms of myelofibrosis such as inflammation and enlargement of the spleen, improve the patient's general physical condition, and prevent complications from occurring after the transplant. Infusing healthy stem cells from a donor into the patient may help the patient's bone marrow work normally and make stem cells, red blood cells, white blood cells, and platelets. Giving a JAK inhibitor before a donor stem cell transplant may help improve transplant outcomes in patients with myelofibrosis.
OUTLINE: PART 1: Patients receive ruxolitinib orally (PO) twice daily (BID) from at least 8 weeks prior to the start of conditioning through day -4 before transplantation, with a taper schedule reducing the dose every 2-3 days beginning after day -4. PART 2: Patients are assigned to 1 of 2 conditioning regimens at the discretion of the clinical provider and Clinical Coordinators Office (CCO). MYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) over 1 hour on days -8 to -6 (umbilical cord blood transplant recipients only), cyclophosphamide IV on days -7 and -6, and busulfan IV over 3 hours on days -5 to -2. REDUCED-INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV over 1 hour on days -6 to -2 and melphalan IV over 15-30 minutes on days -3 and -2. Patients also undergo total-body irradiation (TBI) on day -1 (umbilical cord blood transplant recipients only). TRANSPLANT: Patients undergo allogeneic hematopoietic stem cell transplant or umbilical cord blood transplant on day 0. GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive tacrolimus IV continuously (inpatients) or over 1-2 hours twice daily (BID) (outpatients) or orally (PO) BID on days -1 to +180 (patients receiving related or unrelated stem cells) or days -3 to +180 (patients receiving umbilical cord blood) with taper beginning on day +56 (related donor recipients) or +100 (unrelated donor or umbilical cord blood recipients) in the absence of GVHD. Patients also receive methotrexate IV on days +1, +3, +6, and +11 (related and unrelated donor recipients only) or mycophenolate mofetil IV or PO every 8 hours on days 0 to +40 with taper to day +96 (umbilical cord blood transplant recipients only). After completion of study treatment, patients are followed up at 6 months, 1 year, and then yearly for 4 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
61
Undergo allogeneic hematopoietic stem cell transplant
Given IV
Given IV
Given IV
Correlative studies
Given IV
Given IV
Given IV or PO
Given PO
Given IV or PO
Undergo TBI
Undergo umbilical cord blood transplant
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
2-year Overall Survival (OS) in Patients With Myelofibrosis (MF) Who Receive Treatment With a JAK Inhibitor Followed by an Allogeneic Transplant
OS was defined as the time from date of transplantation to date of death due to any cause. In the absence of confirmation of death, survival time was censored to last date the participant was known to be alive. The 2-year survival probability was estimated using the Kaplan-Meier method and a 2-sided 95% confidence interval (CI).
Time frame: 2 years
Percentage of Participants With Acute Graft Versus Host Disease (GVHD) Grade II-IV
Percentage of Participants with Grade II-IV acute GVHD in the first 100 days post HCT.
Time frame: Up to 100 days post-transplant
Percentage of Participants With Chronic Graft Versus Host Disease (GVHD)
Max grade of chronic GVHD mild, moderate or severe at any time within the first 2 years following transplant.
Time frame: 2 years
Percentage of Patients Who Had Relapsed Disease at 1 Year
Patients who had evidence of residual disease by molecular, flow cytometric or cytogenetics/FISH were considered relapsed disease.
Time frame: 1 year
Non-relapse Mortality (NRM)
Patients who died in remission between day of transplant and day 100.
Time frame: Day 100
Non-relapse Mortality (NRM)
Time frame: 1 year
Number of Patients Who Experienced Primary Graft Failure/Rejection
Patients who failed to achieve ANC \> 500 x 3 or chimerism \> 5% by day 42 post-transplant.
Time frame: Up to 42 days post-transplant
Number of Patients Who Experienced Secondary Graft Failure/Poor Graft Function
Patients who engrafted with an ANC \>500 x 3 or chimerism \> 5% and then became neutropenic with ANC \<500x3 days or chimerism \<5% without evidence of relapse.
Time frame: Up to 5 years
Percentage of Patients With a Max Grade of Moderate and Severe Chronic GVHD at Any Time Before 2 Years Post Transplant.
Includes patients who had a max grade of moderate or severe chronic GVHD by the NIH scoring system at any time between day 0 and 2 years post transplant.
Time frame: 2 years post-HCT
Percentage of Participants With Acute Graft Versus Host Disease Grade III-IV GVHD
Patients who had a max grade of III-IV acute GVHD any time between Day 0 and Day 100.
Time frame: 100 days
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