study of itacitinib for the prophylaxis of graft-versus-host disease and cytokine release syndrome after t-cell replete haploidentical peripheral blood hematopoietic cell transplantation

Conditions: Acute Myelogenous Leukemia; Acute Lymphocytic Leukemia; Myelodysplastic Syndromes; Non-Hodgkin Lymphoma; Hodgkin Disease

Summary: in this trial, the investigators will begin to explore the possibility that, as in mice, janus kinase inhibitor 1 (jak1) inhibition with haploidentical-hematopoietic cell transplantation (hct) may mitigate graft-versus-host-disease (gvhd) and cytokine release syndrome (crs) while retaining graft-versus-leukemia (gvl) and improving engraftment. the purpose of this pilot study is to determine the safety of itacitinib with haplo-hematopoietic cell transplantation (hct) measured by the effect on engraftment and grade iii-iv gvhd.


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 international working group (iwg) criteria) * acute lymphocytic leukemia (all) in complete morphological remission (mrd negative, based on iwg criteria) * myelodysplastic syndrome with ≤ 5% 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 t cell-replete peripheral blood haploidentical donor transplantation * available human leukocyte antigen (hla)-haploidentical donor who meets the following criteria: * blood-related family member, including (but not limited to) sibling, offspring, cousin, nephew, or parent. younger donors should be prioritized. * at least 18 years of age * hla-haploidentical donor/recipient match by at least low-resolution typing per institutional standards. * in the investigator's opinion, is in general good health, and medically able to tolerate leukapheresis required for harvesting hematopoietic stem cells (hsc). * no active hepatitis. * negative for human t-cell lymphotrophic virus (htlv) and human immunodeficiency virus (hiv). * not pregnant. * safety lead-in phase: for the first three patients, the donor 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 * aspartate aminotransferase (ast)(sgot) and alanine aminotransferase (alt) (sgpt) ≤ 3.0 x institutional upper limit of normal (iuln). * creatinine ≤ 1.5 x iuln or creatinine clearance ≥ 45 ml/min/1.73 m\^2 by cockcroft-gault formula. * oxygen saturation ≥ 90% on room air. * left ventricular ejection fraction (lvef) ≥ 40%. * forced expiratory volume (fev1) and forced vital capacity (fvc) ≥ 40% predicted, diffusing capacity of the lung for carbon monoxide (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 institutional review board (irb) approved written informed consent document (or that of legally authorized representative, if applicable). * must be able to receive gvhd prophylaxis with tacrolimus, mycophenolate mofetil, and cyclophosphamide exclusion criteria: * must not have undergone a prior allogeneic donor (related, unrelated, or cord) transplant. prior autologous transplant is not exclusionary. * presence of donor-specific antibodies (dsa) with mean fluorescence intensity (mfi) of ≥2000 as assessed by the single antigen bead assay. * known hiv or active hepatitis b or c infection. * known hypersensitivity to one or more of the study agents, including ruxolitinib and itacitinib. * must not have myelofibrosis (unless they are enrolled amendment #5 or later) or other disease known to prolong neutrophil engraftment to \> 35 days after transplant. * must not receive antithymocyte globulin as part of pre-transplant conditioning regimens. * 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. additional inclusion criteria under amendment 5 * five subjects with myelofibrosis will be enrolled in the expansion phase. * three patients whose donors fail to collect the target number of cd34+ cells and the treating physician choses to move forward with the haplo-hct will be enrolled in the expansion phase.