- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03755414
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 11, 2024 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
Active, not recruiting
Conditions
Study Type
Interventional
Enrollment (Actual)
55
Phase
- 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
- Name: Ramzi Abboud, M.D.
- Phone Number: 314-454-8304
- Email: rabboud@wustl.edu
Study Locations
-
-
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
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 |
Intervention / Treatment |
---|---|
Experimental: Pilot Study: Itacitinib
|
Standard of care
Itacitinib may be taken without regard to food.
|
Experimental: Expansion Phase: Itacitinib
|
Standard of care
Itacitinib may be taken without regard to food.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cumulative incidence of graft failure (pilot study only)
Time Frame: 35 days post haplo-HCT
|
35 days post haplo-HCT
|
|
Cumulative incidence of grades III-IV acute GVHD
Time Frame: 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).
|
Day 100
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participants who experience cytokine release syndrome (CRS)
Time Frame: Through Day 8 (approximately 1 week post transplant)
|
|
Through Day 8 (approximately 1 week post transplant)
|
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).
|
Day 100
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- 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.
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)
September 4, 2019
Primary Completion (Estimated)
June 17, 2024
Study Completion (Estimated)
September 5, 2024
Study Registration Dates
First Submitted
November 20, 2018
First Submitted That Met QC Criteria
November 26, 2018
First Posted (Actual)
November 28, 2018
Study Record Updates
Last Update Posted (Actual)
March 12, 2024
Last Update Submitted That Met QC Criteria
March 11, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Systemic Inflammatory Response Syndrome
- Inflammation
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Shock
- Leukemia, Lymphoid
- Lymphoma
- Syndrome
- Myelodysplastic Syndromes
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Hodgkin Disease
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Graft vs Host Disease
- Cytokine Release Syndrome
Other Study ID 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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