This initial cohort of this phase II trial studied the outcomes of using a JAK inhibitor prior to reduced intensity haploidentical (Haplo) transplantation for the treatment of primary or secondary myelofibrosis (MF). The primary risk of using Haplo HCT in patients with MF is graft failure. In the first cohort, all patients engrafted. There were no instances of graft failure. However, a large number of patients did have graft versus host disease as a complication of their transplant. JAK inhibitors have since been approved for the indication of graft versus host disease treatment. And we are also using them for graft versus host disease prevention in a study of MF patients with sibling and unrelated donors. Therefore, we are opening a new cohort of the current study using the JAK inhibitor prior to, during and after Haplo transplant. Our goal is to decrease graft versus host disease in patients receiving a Haplo MF transplant without increasing the risk of graft failure.
OUTLINE: Cohort 1 is now closed and all patients will be enrolled on Cohort 2. COHORT I: JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of hematopoietic cell transplantation (HCT) conditioning through day -4 before transplantation. CONDITIONING: Patients receive melphalan intravenously (IV) over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo total-body irradiation (TBI) on day -1 or day -1 and day 0. TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0. GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then orally (PO) for about 6 months, mycophenolate mofetil PO twice daily (BID) or three times daily (TID) beginning day 5 for 6 weeks, and granulocyte colony-stimulating factor (G-CSF) subcutaneously (SC) beginning day 7 until neutrophil recovery is \> 1,500/mm\^3. COHORT II: JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation. Additionally, patients receive a JAK inhibitor following transplantation beginning day +5 through 9-12 months after transplant. CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0. TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0. GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is \> 1,500/mm\^3. All patients undergo magnetic resonance imaging (MRI), computed tomography (CT), bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) on the trial. After completion of study treatment, patients are followed up between day 80-100, at 1 year, and then up to 5 years.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Given IV
Given PO
Given IV
Given SC
Given IV
Given PO
Given IV
Given IV and PO
Undergo TBI
Undergo CT
Undergo MRI
Undergo bone marrow biopsy and aspiration
Undergo bone marrow biopsy and aspiration
Undergo blood sample collection
Undergo ECHO
Undergo MUGA
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
RECRUITINGProbability of primary and secondary graft failure
Primary graft failure is defined as failure to achieve an absolute neutrophil count of \> 500/ul by 42 days after bone marrow or peripheral blood stem cell transplantation. Secondary graft failure is defined as cytopenias after initial engraftment, with (a) donor chimerism of \< 5% or (b) falling donor chimerism with intervention such as second transplant or donor lymphocyte infusion or (c) patient death due to cytopenias, and fall in donor chimerism, even if chimerism is \> 5%. Exclusion criteria for diagnosis of graft failure are (a) disease relapse, (b) graft-versus-host disease, and (c) other causes of cytopenias such as, viral infection and drug toxicity.
Time frame: Up to 5 years
Incidence of severe (grade 3 or 4) cytokine release syndrome
Time frame: Up to 5 years
Non-relapse mortality (NRM)
Time frame: Day 100
NRM
Time frame: 1 year
Overall survival
Time frame: 1 year
Overall survival
Time frame: 3 years
Incidence of grade II-IV acute graft versus host disease (GVHD)
Time frame: Up to 5 years
Incidence of grade III-IV acute GVHD
Time frame: Up to 5 years
Incidence of moderate-severe chronic GVHD
Time frame: Up to 5 years
Incidence of relapse
Time frame: At 1 year
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