An Open Label, Non-Randomized, Multi-Center Pilot Dose-Expansion Study of Low Dose Post-Transplant Cyclophosphamide/Tacrolimus/Ruxolitinib for GVHD Prophylaxis in Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation
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
• Patients undergoing allogeneic hematopoietic cell transplantation for one of the following indications:
‣ 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)
• Patients must have a related or unrelated peripheral blood stem cell donor as follows:
‣ Sibling donor must be a 6/6 match for HLA-A and -B at intermediate (or higher) resolution, and -DRB1 at high resolution using DNA-based typing and must be willing to donate peripheral blood stem cells and meet institutional criteria for donation.
⁃ Unrelated donor must be an 8/8 match at HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing.
• Unrelated donor must be willing to donate peripheral blood stem cells and meet National Marrow Donor Program (NMDP) criteria for donation.
• \* Donor selection must comply with 21 CFR 1271
• Cardiac function: Left ventricular ejection fraction at least 45%
• Estimated creatinine clearance greater than 60 ml/min (C-G formula)
• Pulmonary function: DLCO (diffusing capacity of lung for carbon monoxide) corrected for hemoglobin at least 60% and FEV1 (forced expiratory volume at one second) predicted at least 60%
• Liver function: AST(Aspartate aminotransferase)/ALT(Alanine aminotransferase) \<3x Upper Limit of Normal (ULN); Total bilirubin \<2 mg/dL excluding Gilbert's syndrome or hemolysis
• Karnofsky Performance Score at least 70%.
• Female patients (unless postmenopausal for at least 1 year before the screening visit, or surgically sterilized), agree to practice two (2) effective methods of contraception at the same time, or agree to completely abstain from heterosexual intercourse, from the time of signing the informed consent through 12 months post-transplant.
• Male patients (even if surgically sterilized), of partners of women of childbearing potential must agree to one of the following: practice effective barrier contraception or abstain from heterosexual intercourse from the time of signing the informed consent through 12 months post-transplant.
• Plans for the use of targeted small molecule inhibitor post-transplant maintenance therapy must be disclosed upon enrollment. Planned use of investigational maintenance agents is not permitted. Planned hypomethylating agents as maintenance therapy is not permitted.
• Allowed maintenance includes:
• FLT3 inhibitors: gilteritinib, sorafenib, midostaurin
• IDH inhibitors: enasidenib, ivosidenib
• BCR/ABL inhibitors: imatinib, ponatinib, dasatinib, nilotinib
‣ Other targeted therapies may be discussed with protocol chairsVoluntary written consent obtained prior to the performance of any study-related procedure that is not a part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
⁃ There are no restrictions based on blood counts as this intervention is being used in combination with intensive chemotherapy with intent to myeloablate.