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
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
2 other identifiers
interventional
55
1 country
1
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 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Sep 2019
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 20, 2018
CompletedFirst Posted
Study publicly available on registry
November 28, 2018
CompletedStudy Start
First participant enrolled
September 4, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 26, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
May 26, 2024
CompletedResults Posted
Study results publicly available
April 6, 2025
CompletedApril 6, 2025
March 1, 2025
4.6 years
November 20, 2018
February 27, 2025
March 19, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
Number of Participants With Graft Failure (Pilot Study Only)
Failure to engraft will be defined as failure to achieve absolute neutrophil count \>500 for 3 days by day 35.
By day 35
Number of Participants With Grades III-IV Acute GVHD
-Incidence of acute grade III-IV GVHD will be assessed using Mount Sinai Acute GvHD International Consortium (MAGIC) criteria. Attempts should be made to confirm the diagnosis pathologically by biopsy of target organ(s).
Through day 100
Secondary Outcomes (3)
Number of Participants Who Experience Cytokine Release Syndrome (CRS)
Through day 28
Number of Participants With Treatment Related Mortality
Day 180
Cumulative Incidence of Grades II-IV Acute GVHD (Expansion Phase)
Day 100
Study Arms (3)
Pilot Study: Itacitinib
EXPERIMENTAL* Will undergo institutionally standard myeloablative or reduced intensity chemotherapy or chemoradiotherapy * Stem cell transplantation on Day 0 * Itacitinib 200 mg/day from Day -3 to Day 100. After Day 100, for patients at a dose of 200 mg daily, reduce to 100 mg daily for 1 month, then every other day for one month, then discontinue OR after day 100, for patients already dose reduced to 100 mg daily, reduce to 100 mg every other day then discontinue OR after day 100, for patients on study drug hold, discontinue permanently * To address concerns of engraftment failure using itacitinib throughout the transplant period, for the first three patients the investigators will consent the donor for a second CD34+ collection to use as a rescue in the case of engraftment failure.
Expansion Phase: Itacitinib
EXPERIMENTAL* Will undergo institutionally standard myeloablative or reduced intensity chemotherapy or chemoradiotherapy * Stem cell transplantation on Day 0 * Itacitinib 200 mg/day from Day -3 to Day 180. After Day 180, for patients at a dose of 200 mg daily, reduce to 100 mg daily for 1 month, then every other day for one month, then discontinue OR after day 180, for patients already dose reduced to 100 mg daily, reduce to 100 mg every other day then discontinue OR after day 180, for patients on study drug hold, discontinue permanently
Donors
NO INTERVENTION-Donors were consented for the patients enrolled in the Safety Lead-In Phase (planned 3 patients). Donors were consented for a second CD34+ collection to use as a rescue in the case of engraftment failure and for collection of a research blood specimen prior to mobilization.
Interventions
Standard of care
Itacitinib may be taken without regard to food.
* Screening, day 14, day 28, day 42, day 74, day 100, taper period, and follow-up (pilot study) * Screening, day 14, day 28, day 42, day 74, day 100, day 180, taper period, and follow-up period (expansion study)
* Screening, day 14, day 28, day 42, day 74, day 100, taper period, and follow-up (pilot study) * Screening, day 14, day 28, day 42, day 60, day 74, day 100, day 180, taper period, and follow-up period (expansion study)
Eligibility Criteria
You may qualify if:
- 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.
- +12 more criteria
You may not qualify if:
- 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.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Washington University School of Medicinelead
- Incyte Corporationcollaborator
- American Society of Hematologycollaborator
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Related Publications (1)
Abboud R, Schroeder MA, Rettig MP, Jayasinghe RG, Gao F, Eisele J, Gehrs L, Ritchey J, Choi J, Abboud CN, Pusic I, Jacoby M, Westervelt P, Christopher M, Cashen A, Ghobadi A, Stockerl-Goldstein K, Uy GL, DiPersio JF. Itacitinib for prevention of graft-versus-host disease and cytokine release syndrome in haploidentical transplantation. Blood. 2025 Mar 27;145(13):1382-1394. doi: 10.1182/blood.2024026497.
PMID: 39576962DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Ramzi Abboud
- Organization
- Washington University School of Medicine
Study Officials
- PRINCIPAL INVESTIGATOR
Ramzi Abboud, M.D.
Washington University School of Medicine
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 20, 2018
First Posted
November 28, 2018
Study Start
September 4, 2019
Primary Completion
April 26, 2024
Study Completion
May 26, 2024
Last Updated
April 6, 2025
Results First Posted
April 6, 2025
Record last verified: 2025-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL
- Time Frame
- Data will be available beginning 9 months and ending 36 months following article publication
Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices). The study protocol will also be made available. Data will be shared with investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary"), for the purpose of achieving their approved aims. Patient who opt out of data sharing will not be included.