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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03755414
Recruitment Status : Recruiting
First Posted : November 28, 2018
Last Update Posted : September 13, 2019
Incyte Corporation
Information provided by (Responsible Party):
Washington University School of Medicine

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.

Condition or disease Intervention/treatment Phase
Acute Myelogenous Leukemia Acute Lymphocytic Leukemia Myelodysplastic Syndromes Non-Hodgkin Lymphoma Hodgkin Disease Procedure: Stem cell transplantation Drug: Itacitinib Other: Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Other: Human Activity Profile Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single-Arm, Open-Label, Pilot 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
Actual Study Start Date : September 4, 2019
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : September 30, 2022

Arm Intervention/treatment
Experimental: 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, followed by a 1-2 month taper. During the tapering period, itacitinib dose should be decreased to 100 mg daily for 30-60 days then discontinued.
  • 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: Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT)
-Screening, day 14, day 28, day 42, day 100, taper period, and follow-up period

Other: Human Activity Profile
-Screening, day 14, day 28, day 42, day 100, taper period, and follow-up period

Primary Outcome Measures :
  1. Cumulative incidence of graft failure [ Time Frame: 35 days post haplo-HCT ]
  2. Cumulative incidence of grade 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).

Secondary Outcome Measures :
  1. Number of participants who experience cytokine release syndrome (CRS) [ Time Frame: Through Day 8 (approximately 1 week post transplant) ]
    • The number of participants who experience CRS will be summarized by count of participants who experience Grade 1, 2, 3, 4, & 5 CRS.
    • 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

  2. 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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 (MRD negative, based on International Working Group (IWG) Criteria)
    • Acute lymphocytic leukemia (ALL) in complete morphological remission (MRD negative, based on IWG Criteria)
    • Myelodysplastic syndrome with less than 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 who is either a sibling (full or half) or offspring).

      **Other donors will be excluded, including: parent, cousin, niece or nephew, aunt or uncle, and grandparent.

    • 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 ≤ 2.5 mg/dl (unless the patient has a history of Gilbert's syndrome).
    • Aspartate aminotransferase (AST)(SGOT) and alanine aminotransferase (ALT) (SGPT) ≤ 3.0 x institutional upper limit of normal (IULN).
    • Creatinine ≤ 2.0 x IULN OR estimated creatinine clearance ≥ 30 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 anti-HLA antibodies.
  • 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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03755414

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Contact: Mark A Schroeder, M.D. 314-454-8304

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United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Mark A Schroeder, M.D.    314-454-8304   
Principal Investigator: Mark A Schroeder, M.D.         
Sub-Investigator: Ramzi Abboud, M.D.         
Sub-Investigator: John F DiPersio, M.D., Ph.D.         
Sub-Investigator: Peter Westervelt, M.D., Ph.D.         
Sub-Investigator: Camille Abboud, M.D.         
Sub-Investigator: Amanda Cashen, M.D.         
Sub-Investigator: Keith Stockerl-Goldstein, M.D.         
Sub-Investigator: Ravi Vij, M.D.         
Sub-Investigator: Geoffrey Uy, M.D.         
Sub-Investigator: Mathew Walter, M.D.         
Sub-Investigator: Todd Fehniger, M.D., Ph.D.         
Sub-Investigator: Armin Ghobadi, M.D.         
Sub-Investigator: Meagan Jacoby, M.D., Ph.D.         
Sub-Investigator: Iskra Pusic, M.D.         
Sub-Investigator: Lukas Wartman, M.D.         
Sub-Investigator: John Welch, M.D., Ph.D.         
Sub-Investigator: Tanya Wildes, M.D.         
Sub-Investigator: Terrence Wong, M.D., Ph.D.         
Sub-Investigator: Francesca Ferraro, M.D., Ph.D.         
Sponsors and Collaborators
Washington University School of Medicine
Incyte Corporation
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Principal Investigator: Mark A Schroeder, M.D. Washington University School of Medicine

Additional Information:
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Responsible Party: Washington University School of Medicine Identifier: NCT03755414     History of Changes
Other Study ID Numbers: 201903114
First Posted: November 28, 2018    Key Record Dates
Last Update Posted: September 13, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Time Frame: Data will be available beginning 9 months and ending 36 months following article publication

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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
Additional relevant MeSH terms:
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Leukemia, Myeloid, Acute
Hodgkin Disease
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Myelodysplastic Syndromes
Graft vs Host Disease
Pathologic Processes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Lymphoid
Leukemia, Myeloid