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

March 19, 2025 updated by: Washington University School of Medicine

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
55

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Pilot Study: Itacitinib
  • 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.
Procedure: Stem cell transplantation
Standard of care
Drug: Itacitinib
Itacitinib may be taken without regard to food.
Other: Human Activity Profile
  • 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)
Other: Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT)
  • 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)
Experimental: Expansion Phase: Itacitinib
  • 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
Procedure: Stem cell transplantation
Standard of care
Drug: Itacitinib
Itacitinib may be taken without regard to food.
Other: Human Activity Profile
  • 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)
Other: Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT)
  • 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)
No Intervention: Donors
-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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Graft Failure (Pilot Study Only)
Time Frame: By day 35
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
Time Frame: Through day 100
-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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants Who Experience Cytokine Release Syndrome (CRS)
Time Frame: Through day 28
  • The number of participants who experience CRS will be summarized by count of participants who experience Grade 1, 2, 3, 4, & 5 CRS. The worst grade experienced by participant will be noted.
  • Grade 1: symptoms not life threatening & require symptomatic treatment alone, includes fever, nausea, fatigue, malaise
  • Grade 2: symptoms require/respond to limited intervention - oxygen (O2) <40%, <=3 liters (L) nasal cannula or hypotension responsive to fluids or low dose of 1 vasopressor or grade 2 renal or hepatic toxicity
  • Grade 3: symptoms require/respond to aggressive intervention - O2 >=40%, >3L nasal cannula or hypotension requiring high dose or multiple vasopressors or grade 3 renal toxicity or grade 4 transaminitis, new onset altered mental status, new cardiomyopathy without wall motion abnormality
  • Grade 4: life-threatening symptoms - requirement for ventilator support or grade 4 rental toxicity (excluding transaminitis)
  • Grade 5: death
Through day 28
Number of Participants With Treatment Related Mortality
Time Frame: Day 180
-Death that results from a transplant procedure-related complication (e.g. infection, organ failure, hemorrhage, GVHD) rather than from relapse of the underlying disease or an unrelated cause
Day 180
Cumulative Incidence of Grades II-IV Acute GVHD (Expansion Phase)
Time Frame: Day 100
  • Incidence of acute grade II-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).
  • The cumulative incidence of aGVHD was estimated using Fine-Gray's sub-distribution methods to account for competing risk of death without aGVHD.
Day 100

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Washington University School of Medicine

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)
Incyte Corporation
American Society of Hematology

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ramzi Abboud, M.D., Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 4, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 26, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 26, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 20, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 26, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 28, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 6, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 19, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 201903114
  • K12CA167540 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

IPD Sharing Time Frame

Data will be available beginning 9 months and ending 36 months following article publication

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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