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

NCT ID: NCT03755414

Last Updated: 2025-04-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-04
• Study Completion Date: 2024-05-26

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.

Conditions

Acute Myelogenous Leukemia; Acute Lymphocytic Leukemia; Myelodysplastic Syndromes; Non-Hodgkin Lymphoma; Hodgkin Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Stem cell transplantation

Intervention Type: PROCEDURE

Standard of care

Itacitinib

Intervention Type: DRUG

Itacitinib may be taken without regard to food.

Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT)

Intervention Type: OTHER

• 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)

Human Activity Profile

Intervention Type: OTHER

• 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)

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

Group Type: EXPERIMENTAL

Stem cell transplantation

Intervention Type: PROCEDURE

Standard of care

Itacitinib

Intervention Type: DRUG

Itacitinib may be taken without regard to food.

Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT)

Intervention Type: OTHER

• 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)

Human Activity Profile

Intervention Type: OTHER

• 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)

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Stem cell transplantation

Standard of care

Intervention Type: PROCEDURE

Itacitinib

Itacitinib may be taken without regard to food.

Intervention Type: DRUG

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)

Intervention Type: 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)

Intervention Type: OTHER

Eligibility Criteria

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

• 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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Incyte Corporation

INDUSTRY

Sponsor Role: collaborator

American Society of Hematology

OTHER

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ramzi Abboud, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 39576962 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

http://www.siteman.wustl.edu

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Other Identifiers

K12CA167540

Identifier Type: NIH

Identifier Source: secondary_id

View Link

201903114

Identifier Type: -

Identifier Source: org_study_id