baricitinib for the prophylaxis of graft-versus-host disease after peripheral blood hematopoietic cell transplantation

Conditions: Graft-versus-host-disease; Graft Vs Host Disease

Summary: in this trial, the investigators will begin to explore the possibility that, as in mice, jak1/2 inhibition with hematopoietic cell transplantation (hct) may mitigate graft-versus-host-disease (gvhd) while retaining engraftment and graft-versus-leukemia (gvl). both preclinical and clinical data suggest that inhibition of ifny and il-6, directly and using downstream jak inhibitors, may be an effective strategy to decrease toxicities and improve disease control for patients undergoing allogeneic hsct. baricitinib, as a jak1/2 inhibitor, has shown superiority to other jak inhibitors in preclinical gvhd models. the purpose of this phase i clinical trial is to determine the safety of baricitinib with hsct measured by the effect on engraftment and grade iii-iv acute graft-versus-host-disease (agvhd).


Eligibility criteria:
inclusion criteria: patients must meet the following criteria within 30 days prior to day 0 unless otherwise noted. * diagnosis of a hematological malignancy listed below: * acute myelogenous leukemia (aml) in complete morphological remission (based on iwg criteria). * acute lymphocytic leukemia (all) in complete morphological remission (mrd negative, based on iwg criteria). * myelodysplastic syndrome with less than 10% blasts in bone marrow. * non-hodgkin's lymphoma (nhl) or hodgkin's disease (hd) in 2nd or greater complete or partial remission. * planned treatment is myeloablative or reduced intensity conditioning followed by peripheral blood hla matched donor transplantation * available hla-identical donor who meets the following criteria: * at least 18 years of age. * hla-identical donor/recipient match by high-resolution typing per institutional standards. * in the investigator's opinion, is in general good health, and medically able to tolerate leukapheresis required for harvesting hsc. * no active hepatitis. * negative for htlv and hiv. * not pregnant. * donor selection will be in compliance with institutional standards * safety lead-in phase: for the first three patients at each dose level, related donors must consent to a second product collection should it prove necessary. * eastern cooperative oncology group (ecog) performance status ≤ 2 * adequate organ function as defined below: * total bilirubin must be within normal range at baseline. * ast (sgot) and alt (sgpt) ≤ 3.0 x iuln. * estimated creatinine clearance ≥ 60 ml/min/1.73 m2 by cockcroft-gault formula. * oxygen saturation ≥ 90% on room air. * lvef ≥ 40%. * fev1 and fvc ≥ 40% predicted, dlcoc ≥ 40% predicted. if dlco is \< 40%, patients will still be considered eligible if deemed safe after a pulmonary evaluation. * at least 18 years of age at the time of study registration * able to understand and willing to sign an irb approved written informed consent document (or that of legally authorized representative, if applicable). * must be able to receive gvhd prophylaxis with tacrolimus, mini-methotrexate with or without atg or post transplant cy with mmf and tacrolimus as outlined in the protocol exclusion criteria: * must not have undergone a prior allogeneic donor (related, unrelated, or cord) transplant. prior autologous transplant is not exclusionary. * known hiv or active hepatitis b or c infection. * known latent tuberculosis infection, or at high risk for latent tb infection, or a positive t-spot tuberculosis test * known hypersensitivity to one or more of the study agents, including baricitinib. * must not have myelofibrosis or other disease known to prolong neutrophil engraftment to \> 35 days after transplant. * currently receiving or has received any investigational drugs within the 14 days prior to the first dose of study drug (day -3). * pregnant and/or breastfeeding. * uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, autoimmune disease, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmias, or psychiatric illness/social situations that would limit compliance with study requirements. * immunosuppressive doses of steroids. subjects with steroids for adrenal insufficiency will not be excluded. * history of unprovoked thrombosis or known thrombophilia. provoked and/or superficial dvts are eligible provided they are treated and resolved at the time of screening. * recent (less than 1 year from screening) myocardial infarction or embolic stroke