Clinical Trial: JAK Inhibitor Before Donor Stem Cell Transplant in Treating Patients With Primary or Secondary Myelofibrosis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: JAK Inhibitor Prior to Allogeneic Stem Cell Transplant for Patients With Primary and Secondary Myelofibrosis: A Prospective Study

Brief Summary: 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 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.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To optimize the role of allogeneic transplantation for primary and secondary myelofibrosis (MF) in the JAK inhibitor era.

OUTLINE:

PART 1: Patients receive a JAK inhibitor (ruxolitinib, momelotinib, or pacritinib) 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)
Sponsor: Fred Hutchinson Cancer Research Center

Current Primary Outcome: Probability of 2-year survival in patients with MF who receive treatment with a JAK inhibitor followed by an allogeneic transplant [ Time Frame: 2 years ]

The exact benchmark that will be used for comparison will be determined from the mix of 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.


Original Primary Outcome: Probability of 2-year survival in patients with MF who receive treatment with a JAK-2 inhibitor followed by an allogeneic transplant [ Time Frame: 2 years ]

The exact benchmark that will be used for comparison will be determined from the mix of DIPSS categories among those enrolled and treated with JAK-2 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.


Current Secondary Outcome:

  • Biology of post transplant disease progression [ Time Frame: Up to 5 years ]
  • Incidence and severity of acute 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 ]
  • Kinetics of donor chimerism [ Time Frame: Up to 5 years ]
  • Mechanism of responses to JAK inhibitors [ Time Frame: Up to 5 years ]
  • Neutrophil engraftment, defined as the first of 3 days absolute neutrophil count (ANC) >= 500 [ Time Frame: Up to 5 years ]
  • Non-relapse mortality (NRM) [ Time Frame: Day 100 ]
  • 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 ]
  • Overall survival [ Time Frame: Up to 5 years ]
  • Platelet engraftment defined as first day of 20,000 and 50,000 with no transfusions x 7 days [ Time Frame: Up to 5 years ]


Original Secondary Outcome:

  • 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 ]
  • Kinetics of donor chimerism [ Time Frame: Up to 5 years ]
  • Time to absolute neutrophil count (ANC) greater than or equal to 100 [ Time Frame: Up to 5 years ]
  • Time to ANC greater than or equal to 500 [ Time Frame: Up to 5 years ]
  • Time to platelet engraftment (20,000) [ Time Frame: Up to 5 years ]
  • Time to platelet engraftment (50,000) [ Time Frame: Up to 5 years ]
  • Non-relapse mortality (NRM) [ Time Frame: Day 100 ]
  • NRM [ Time Frame: 1 year ]
  • Incidence of relapse [ Time Frame: 1 year ]
  • Incidence and severity of acute GVHD [ Time Frame: Up to 70 days post-transplant ]
  • Incidence and severity of chronic GVHD [ Time Frame: Up to 2 years ]
  • Overall survival [ Time Frame: Up to 5 years ]
  • Kinetics of chimerism assessed by isolation of CD3+, CD33+ and CD56+ cells from peripheral blood [ Time Frame: Up to 2 years ]
  • Presence of donor and patient cells (mixed chimerism) in bone marrow [ Time Frame: Up to 2 years ]
  • Immunoglobulin levels [ Time Frame: Up to 2 years ]


Information By: Fred Hutchinson Cancer Research Center

Dates:
Date Received: September 12, 2014
Date Started: October 2014
Date Completion:
Last Updated: May 22, 2017
Last Verified: May 2017