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

NCT04131738 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 201911012
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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 phase I clinical trial 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).

Conditions

Graft-versus-host-disease; Graft Vs Host Disease

Outcome Measures

Primary Outcomes (2)

• Cumulative incidence of graft failure

  -Failure to engraft will be defined as failure to achieve absolute neutrophil count \> 500 for 3 days by Day 28.

  28 days post transplant

• Cumulative incidence of grade III-IV acute GVHD

  -Acute GVHD will be assessed using MAGIC criteria

  Day 100

Secondary Outcomes (1)

• Treatment related mortality

  Day 180

Study Arms (2)

Baricitinib 2 mg Dose Level

EXPERIMENTAL

* 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 or 1 mg daily for one month (depending on drug supply) then discontinue.

Drug: Baricitinib

Baricitinib 4 mg Dose Level

EXPERIMENTAL

* 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 or 1 mg daily for one month (depending on drug supply) then discontinue.

Drug: Baricitinib

Interventions

Baricitinib DRUG

Baricitinib may be taken without regard to food. It should be taken at the same time every day.

Also known as: Olumiant

Baricitinib 2 mg Dose Level; Baricitinib 4 mg Dose Level

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 IWG Criteria).
• Acute lymphocytic leukemia (ALL) in complete morphological remission (MRD negative, based on IWG Criteria).
• Myelodysplastic syndrome with less than 10% 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 institutional standards

You may not qualify if:

• Known HIV or active hepatitis B or C infection.
• Known latent tuberculosis infection, or at high risk for latent TB infection, or a positive t-spot tuberculosis 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.
• 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 unprovoked thrombosis or known thrombophilia. Provoked and/or superficial DVTs are eligible provided they are treated and resolved at the time of screening.
• Recent (less than 1 year from screening) myocardial infarction or embolic stroke

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

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

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

baricitinib

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Mark A Schroeder, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: * 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.

Study Record Dates

• First Submitted: October 16, 2019
• First Posted: October 18, 2019
• Study Start: April 7, 2020
• Primary Completion: November 30, 2021
• Study Completion: August 17, 2022
• Last Updated: May 10, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)