A Single-Arm, Open-Label, Pilot Study and Expansion Study of JAK Inhibitor Itacitinib for the Prophylaxis of Graft-Versus-Host Disease and Cytokine Release Syndrome After T-cell Replete Haploidentical Peripheral Blood Hematopoietic Cell Transplantation ITACITINIB IN GRAFT VERSUS HOST DISEASE PREVENTION

What's the purpose of this trial?

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.

This trial is currently open and accepting patients.

What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

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.

Additional Trial Information

Phase 1

Enrollment: 55 patients (estimated)

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Washington University School of Medicine

Saint Louis, MO

Open and Accepting
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