Status:
COMPLETED
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
Lead Sponsor:
Washington University School of Medicine
Collaborating Sponsors:
Incyte Corporation
American Society of Hematology
Conditions:
Acute Myelogenous Leukemia
Acute Lymphocytic Leukemia
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief 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 mit...
Eligibility Criteria
Inclusion
- 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
- 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.
Key Trial Info
Start Date :
September 4 2019
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
May 26 2024
Estimated Enrollment :
55 Patients enrolled
Trial Details
Trial ID
NCT03755414
Start Date
September 4 2019
End Date
May 26 2024
Last Update
April 6 2025
Active Locations (1)
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1
Washington University School of Medicine
St Louis, Missouri, United States, 63110