NCT03755414 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1
Status at capture: COMPLETED
Registry last update: 2025-04-06

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Participants With Graft Failure (Pilot Study Only)

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outcome · POSTED

Number of Participants With Grades III-IV Acute GVHD

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outcome · POSTED

Number of Participants Who Experience Cytokine Release Syndrome (CRS)

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outcome · POSTED

Number of Participants With Treatment Related Mortality

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outcome · POSTED

Cumulative Incidence of Grades II-IV Acute GVHD (Expansion Phase)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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 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.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
* 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.
intervention Names
Procedure: Stem cell transplantation
Drug: Itacitinib
Other: Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT)
Other: Human Activity Profile
label
Pilot Study: Itacitinib
type
EXPERIMENTAL
description
* 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
intervention Names
Procedure: Stem cell transplantation
Drug: Itacitinib
Other: Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT)
Other: Human Activity Profile
label
Expansion Phase: Itacitinib
type
EXPERIMENTAL
description
-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.
label
Donors
type
NO_INTERVENTION

interventions

arm Group Labels
Expansion Phase: Itacitinib
Pilot Study: Itacitinib
description
Standard of care
name
Stem cell transplantation
type
PROCEDURE
arm Group Labels
Expansion Phase: Itacitinib
Pilot Study: Itacitinib
description
Itacitinib may be taken without regard to food.
name
Itacitinib
type
DRUG
arm Group Labels
Expansion Phase: Itacitinib
Pilot Study: Itacitinib
description
* 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)
name
Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT)
type
OTHER
arm Group Labels
Expansion Phase: Itacitinib
Pilot Study: Itacitinib
description
* 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)
name
Human Activity Profile
type
OTHER

Study design

allocation

NON_RANDOMIZED

intervention Model

SEQUENTIAL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 55
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Failure to engraft will be defined as failure to achieve absolute neutrophil count \>500 for 3 days by day 35.
measure
Number of Participants With Graft Failure (Pilot Study Only)
time Frame
By day 35
description
-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).
measure
Number of Participants With Grades III-IV Acute GVHD
time Frame
Through day 100

secondary Outcomes

description
* 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
measure
Number of Participants Who Experience Cytokine Release Syndrome (CRS)
time Frame
Through day 28
description
-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
measure
Number of Participants With Treatment Related Mortality
time Frame
Day 180
description
* 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.
measure
Cumulative Incidence of Grades II-IV Acute GVHD (Expansion Phase)
time Frame
Day 100

Full study description

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.

Source references

references

citation
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
39576962
type
DERIVED