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Baricitinib for the Prophylaxis of Graft-Versus-Host Disease After Peripheral Blood Hematopoietic Cell Transplantation

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ClinicalTrials.gov Identifier: NCT04131738
Recruitment Status : Not yet recruiting
First Posted : October 18, 2019
Last Update Posted : October 18, 2019
Sponsor:
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, JAK1/2 inhibition with hematopoietic cell transplantation (HCT) may mitigate graft-versus-host-disease (GVHD) while retaining engraftment and Graft-versus-Leukemia (GVL). Both preclinical and clinical data suggest that inhibition of IFNy and IL-6, directly and using downstream JAK Inhibitors, may be an effective strategy to decrease toxicities and improve disease control for patients undergoing Allogeneic HSCT. Baricitinib, as a JAK1/2 inhibitor, has shown superiority to other JAK inhibitors in preclinical GVHD models. The purpose of this pilot study is to determine the safety of baricitinib with HSCT measured by the effect on engraftment and grade III-IV acute graft-versus-host-disease (aGVHD).

Condition or disease Intervention/treatment Phase
Graft-versus-host-disease Graft Vs Host Disease Drug: Baricitinib Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
  • If all 3 patients in the safety lead-in for the 2 mg dose level achieve engraftment, 9 additional patients will be enrolled at that dose level.
  • If all 3 patients in the safety lead-in for the 4 mg dose level achieve engraftment, 9 additional patients will be enrolled at that dose level.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Baricitinib for the Prophylaxis of Graft-Versus-Host Disease After Peripheral Blood Hematopoietic Cell Transplantation
Estimated Study Start Date : January 31, 2020
Estimated Primary Completion Date : April 30, 2021
Estimated Study Completion Date : July 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Baricitinib 2 mg Dose Level
  • On Day 0 the allograft will be infused per standard institutional practice
  • Baricitinib will be administered PO at a starting dose of 2 mg daily from Day -3 to Day 100
  • After Day 100, for patients already dose reduced to 2 mg daily, reduce baricitinib to 2 mg every other day for one month then discontinue.
Drug: Baricitinib
Baricitinib may be taken without regard to food. It should be taken at the same time every day.
Other Name: Olumiant

Experimental: Baricitinib 4 mg Dose Level
  • On Day 0 the allograft will be infused per standard institutional practice
  • Baricitinib will be administered PO at a starting dose of 4 mg daily from Day -3 to Day 100
  • After Day 100, for patients at a dose of 4 mg daily, reduce baricitinib to 2 mg daily for one month, then every other day for one month, then discontinue.
Drug: Baricitinib
Baricitinib may be taken without regard to food. It should be taken at the same time every day.
Other Name: Olumiant




Primary Outcome Measures :
  1. Cumulative incidence of graft failure [ Time Frame: 28 days post transplant ]
    -Failure to engraft will be defined as failure to achieve absolute neutrophil count > 500 for 3 days by Day 28.

  2. Cumulative incidence of grade III-IV acute GVHD [ Time Frame: Day 100 ]
    -Acute GVHD will be assessed using MAGIC criteria


Secondary Outcome Measures :
  1. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 (MRD negative, based on 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 peripheral blood HLA matched donor transplantation
  • Available HLA-identical donor who meets the following criteria:

    • At least 18 years of age.
    • HLA-identical donor/recipient match by high-resolution typing per institutional standards.
    • In the investigator's opinion, is in general good health, and medically able to tolerate leukapheresis required for harvesting HSC.
    • No active hepatitis.
    • Negative for HTLV and HIV.
    • Not pregnant.
    • Donor selection will be in compliance with FDA guidelines as provided in 21 CFR 1271 for donor eligibility https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Tissue/UCM091345.pdf
    • 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.
    • AST (SGOT) and ALT (SGPT) ≤ 3.0 x IULN.
    • Estimated creatinine clearance ≥ 60 mL/min/1.73 m2 by Cockcroft-Gault Formula.
    • Oxygen saturation ≥ 90% on room air.
    • LVEF ≥ 40%.
    • FEV1 and FVC ≥ 40% predicted, 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 IRB approved written informed consent document (or that of legally authorized representative, if applicable).
  • Must be able to receive GVHD prophylaxis with tacrolimus, mini-methotrexate as outlined in in protocol

Exclusion Criteria:

  • Must not have undergone a prior allogeneic donor (related, unrelated, or cord) transplant. Prior autologous transplant is not exclusionary.
  • Known HIV or active hepatitis B or C infection.
  • Known latent tuberculosis infection, or at high risk for latent TB infection, or a positive QuantiFERON test
  • Known hypersensitivity to one or more of the study agents, including baricitinib.
  • 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. Antithymocyte globulin is excluded due to its potential impact on modulating the incidence of GvHD or GvL and added risk for infection.
  • 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.
  • History of thrombosis or known thrombophilia.
  • Recent (less than 1 year from screening) myocardial infarction or embolic stroke

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 ClinicalTrials.gov identifier (NCT number): NCT04131738


Contacts
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Contact: Mark A Schroeder, M.D. 314-454-8304 markschroeder@wustl.edu

Locations
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United States, Missouri
Washington University School of Medicine Not yet recruiting
Saint Louis, Missouri, United States, 63110
Contact: Mark A Schroeder, M.d.    314-454-8304    markschroeder@wustl.edu   
Principal Investigator: Mark A Schroeder, M.D.         
Sub-Investigator: Jordan Atkins, M.D., M.P.H.S.         
Sub-Investigator: Himachandana Atluri, M.D.         
Sub-Investigator: Camille Abboud, M.D.         
Sub-Investigator: Amanda Cashen, M.D.         
Sub-Investigator: John F DiPersio, M.D., Ph.D.         
Sub-Investigator: Todd Fehniger, M.D., Ph.D.         
Sub-Investigator: Francesca Ferraro, 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: Keith Stockerl-Goldstein, M.D.         
Sub-Investigator: Geoffrey Uy, M.D.         
Sub-Investigator: Ravi Vij, M.D.         
Sub-Investigator: Mathew Walter, M.D.         
Sub-Investigator: Lukas Wartman, M.D.         
Sub-Investigator: John Welch, M.D., Ph.D.         
Sub-Investigator: Peter Westervelt, M.D., Ph.D.         
Sub-Investigator: Tanya Wildes, M.D.         
Sub-Investigator: Terrence Wong, M.D., Ph.D.         
Sub-Investigator: Feng Gao, Ph.D.         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
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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
ClinicalTrials.gov Identifier: NCT04131738     History of Changes
Other Study ID Numbers: 19-x349
First Posted: October 18, 2019    Key Record Dates
Last Update Posted: October 18, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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.: No
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases