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

• Status: Recruiting
• Trial end date: 2023-08-27
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Washington University School of Medicine
• Collaborators: American Society of Hematology; Incyte Corporation

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 less than 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 who is either a sibling (full or half), offspring, or parent - however, parent donors should not be used if another haploidentical donor is available

**Other donors will be excluded, including: cousin, niece or nephew, aunt or uncle, and grandparent.

• 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 ≥1000 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 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.