This is an open label, non-randomized, multicenter, pilot, dose expansion study of low dose post-transplant cyclophosphamide (25 mg/kg on Days +3 and +4)/tacrolimus/ruxolitinib in the setting of myeloablative conditioning (MAC) allogeneic peripheral blood stem cell transplantation (PBSCT).
Age 18.0 years or older at the time of enrollment
Acute leukemia with no circulating blasts and with less than 5% blasts in the bone marrow
Myelodysplasia/chronic myelomonocytic leukemia with no circulating blasts and with less than 10% blasts in the bone marrow (higher blast percentage allowed in MDS due to lack of differences in outcomes with <5% versus 5-10% blasts in this disease).
Planned myeloablative (MAC) conditioning regimen (see eligible regimens in Section 9.2)
Prior allogeneic transplant
Active CNS (central nervous system) involvement by malignant cells
Patients with secondary acute myeloid leukemia arising from myeloproliferative neoplasms or overlap syndromes, including CMML(chronic myelomonocytic leukemia) and MDS/MPN (myelodysplastic syndromes/myeloproliferative neoplasms) syndromes; patients with secondary acute myeloid leukemia arising from myelodysplastic neoplasm are eligible.
Patients with uncontrolled bacterial, viral, or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment.
Sequential
Ruxolitinib
DrugTaken PO
Myeloablative conditioning regimen
DrugPatients will receive a full-intensity myeloablative conditioning regimen. Allowed regimens include: * Flu/Bu(130 mg/m2/day x 4 days) * Flu/TBI (8-12Gy) * Flu/Bu/Thiotepa The addition of alemtuzumab or ATG is not allowed.
Hematopoietic Stem Cell Transplantation
Procedure/SurgeryPatients will undergo HCT
Cyclophosphamide
DrugGiven IV
Tacrolimus
DrugGiven PO
Severe acute GVHD-free Survival (SGFS)
SGFS will be calculated from the time of transplant to onset of grade 3-4 acute GVHD or death censoring patients alive without grade 3-4 GVHD at last clinical assessment date. The SGFS rate together with 95% confidence interval at day 180 will be estimated by Kaplan-Meier method.
GVHD, relapse free survival (GRFS)
GVHD-free, relapse-free survival as a time to event outcome is defined as Grade III-IV acute GVHD, chronic GVHD requiring systemic immune suppression, underlying disease relapse or progression, or death by any cause.
Grade II-IV acute GVHD and Grade III-IV acute GVHD
Cumulative incidences of Grade II-IV and III-IV acute GVHD will be determined. Acute GVHD will be graded according to standard MAGIC criteria. The time of onset of acute Grades II-IV and III-IV acute GVHD will be recorded, as well as the maximum grade achieved. Within the participants experiencing Grade II-IV acute GVHD, the proportion of patients with visceral involvement (liver or gut) will be described. Cumulative incidences of Minnesota standard and high risk acute GVHD will also be determined.
Chronic GVHD requiring immunosuppression
Rate of chronic GVHD requiring immunosupression at 1 year
GVHD Free Survival (GFS)
Events for this time to event outcome is defined as any of the following: 1) Grade III-IV acute GVHD, 2) chronic GVHD requiring systemic immune suppression, or 3) death by any cause. The time to the event is defined as the time to the earliest of the qualifying events. Subjects alive without experiencing an event will be censored at last available GVHD assessment
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Hannah Choe, MD
Lead sponsor
Ohio State University Comprehensive Cancer Center
Sponsor institution
Incyte Corporation
Collaborator
