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

Graft Vs Host Disease Clinical Trial

Official title:

A Single-Arm, Open-Label Phase I Clinical Trial of a JAK Inhibitor, Baricitinib, for the Prophylaxis of Graft-Versus-Host Disease After Peripheral Blood Hematopoietic Cell Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04131738
• Other study ID #: 201911012
• Status: Completed
• Phase: Phase 1
• Start date: April 7, 2020
• Est. completion date: August 17, 2022

Study information

• Verified date: May 2023
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: August 17, 2022
• Est. primary completion date: November 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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

• Safety Lead-In Phase: For the first three patients at each dose level, related donors 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 with or without ATG or post transplant Cy with MMF and tacrolimus as outlined in the 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 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

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Cumulative incidence of grade III-IV acute GVHD	-Acute GVHD will be assessed using MAGIC criteria	Day 100
Secondary	Treatment related mortality	-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.	Day 180

External Links

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