This phase II trial determines whether a graft versus host disease (GVHD) prevention (prophylaxis) regimen where the drug cyclosporine is discontinued 60 days after first donor bone marrow transplant (BMT) works in patients with lymphoid and myeloid cancers. When patients get a transplant, the transplanted cells see the patient's body as different and will try to fight the patient's body. The symptoms of this fight can be bad and make patients very sick. As a group, the symptoms are called GVHD. The GVHD symptoms can happen just about anywhere in the body. They can happen right away or later. To decrease the chance of getting GVHD, doctors normally give patients a drug called cyclosporine A (CsA) until day 100 post-transplant and methotrexate. CsA is a calcineurin inhibitor (CNI) drug and works in a certain way. CsA has many side effects which increases risk for complications during transplant. Also, it affects the ability of the donor lymphocytes to kill leukemia cells. Ruxolitinib works in a different way than CsA and is well tolerated. It also does not affect the ability of the donor lymphocytes to kill leukemia cells. In this study, patients are given CsA until day 60 only, and ruxolitinib is added on day 40. This new regimen of CsA with methotrexate and ruxolitinib may decrease the chance of patients getting GVHD symptoms.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT05579769.
PRIMARY OBJECTIVE:
I. To estimate the incidence of severe acute GVHD (saGVHD) using a prophylaxis regimen with no calcineurin inhibitors after day +60 post first allogeneic Human Leukocyte antigen (HLA)-matched sibling or unrelated donor HCT for hematological malignancies.
SECONDARY OBJECTIVE:
I. Determine the cumulative incidence of relapse, non-relapse mortality (NRM), chronic GVHD, and overall survival (OS) in study participants at one year post-transplant.
EXPLORATORY OBJECTIVES:
I. To evaluate the pharmacokinetic/pharmacodynamic (PK/PD) profiles of ruxolitinib, fludarabine, and lapine T-lymphocyte immune globulin (rabbit anti-thymocyte globulin [rATG]).
II. To assess immune reconstitution in study participants within the first year post-HCT.
OUTLINE:
CONDITIONING REGIMEN: Patients are assigned to 1 of 2 arms.
ARM I (HEMATOLOGICAL MALIGNANCIES OF LYMPHOID LINEAGE): Patients undergo fractionated total-body irradiation (TBI) and receive cyclophosphamide intravenously (IV) during the Conditioning Regimen portion of the study. Patients with a matched unrelated donor (MUD) also receive rATG IV during the Conditioning Regimen portion of the study. Patients then receive bone marrow infusion on day 0.
ARM II (MYELOID CANCER): Patients receive the TBF regimen, consisting of thiotepa IV, busulfan IV, and fludarabine IV throughout the Conditioning Regimen portion of the study. Patients with a MUD also receive rATG IV during the Conditioning Regimen portion of the study. Patients then receive bone marrow infusion on day 0.
GVHD PROPHYLAXIS: After the bone marrow infusion, all patients receive CsA IV in combination with methotrexate IV and ruxolitinib orally (PO) during the GVHD Prophylaxis portion of the study.
Patients also undergo collection of blood throughout the trial.
Lead OrganizationSaint Jude Children's Research Hospital
Principal InvestigatorAshok Srinivasan
