JAK Inhibitor Before Donor Stem Cell Transplant in Treating Patients With Primary or Secondary Myelofibrosis
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|ClinicalTrials.gov Identifier: NCT02251821|
Recruitment Status : Recruiting
First Posted : September 29, 2014
Last Update Posted : March 28, 2019
|Condition or disease||Intervention/treatment||Phase|
|Primary Myelofibrosis Secondary Myelofibrosis||Procedure: Allogeneic Hematopoietic Stem Cell Transplantation Drug: Busulfan Drug: Cyclophosphamide Drug: Fludarabine Phosphate Other: Laboratory Biomarker Analysis Drug: Melphalan Drug: Methotrexate Drug: Mycophenolate Mofetil Drug: Ruxolitinib Drug: Tacrolimus Radiation: Total-Body Irradiation Procedure: Umbilical Cord Blood Transplantation||Phase 2|
I. To optimize the role of allogeneic transplantation for primary and secondary myelofibrosis (MF) in the JAK inhibitor era.
PART 1: Patients receive a ruxolitinib orally (PO) twice daily (BID) from at least 8 weeks prior to the start of conditioning until best response 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 (Clinical Trial)|
|Estimated Enrollment :||48 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||JAK Inhibitor Prior to Allogeneic Stem Cell Transplant for Patients With Primary and Secondary Myelofibrosis: A Prospective Study|
|Actual Study Start Date :||October 20, 2014|
|Estimated Primary Completion Date :||March 11, 2021|
|Estimated Study Completion Date :||March 11, 2024|
Experimental: Treatment (ruxolitinib, transplant)
Patients receive a ruxolitinib and undergo myeloablative or reduced-intensity conditioning followed by transplant and GVHD prophylaxis; see detailed description.
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic hematopoietic stem cell transplant
Drug: Fludarabine Phosphate
Other: Laboratory Biomarker Analysis
Drug: Mycophenolate Mofetil
Given IV or PO
Given IV or PO
Radiation: Total-Body Irradiation
Procedure: Umbilical Cord Blood Transplantation
Undergo umbilical cord blood transplant
- Probability of 2-year survival in patients with myelofibrosis (MF) who receive treatment with a JAK inhibitor followed by an allogeneic transplant [ Time Frame: At 2 years ]The exact benchmark that will be used for comparison will be determined from the mix of Dynamic International Prognostic Scoring System (DIPSS) categories among those enrolled and treated with JAK on the current trial. From this mix, an expected two-year survival will be created as a weighted average of the data cited above. This weighted average will be used as the benchmark to which the data from the current trial will be compared.
- Incidence and severity of acute graft versus host disease (GVHD) [ Time Frame: Up to 70 days post-transplant ]
- Incidence and severity of chronic GVHD [ Time Frame: Up to 2 years ]
- Incidence of relapse [ Time Frame: 1 year ]
- Non-relapse mortality (NRM) [ Time Frame: Day 100 ]
- Non-relapse mortality (NRM) [ Time Frame: 1 year ]
- Overall incidence of primary graft failure/rejection [ Time Frame: Up to 5 years ]
- Overall incidence of secondary graft failure/rejection [ Time Frame: Up to 5 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02251821
|United States, Washington|
|Fred Hutch/University of Washington Cancer Consortium||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: Rachel B. Salit 206-667-1317 email@example.com|
|Principal Investigator: Rachel B. Salit|
|Principal Investigator:||Rachel Salit||Fred Hutch/University of Washington Cancer Consortium|