Study of Baricitinib, a JAK1/2 Inhibitor, in Chronic Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

NCT02759731 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 16009416-C-0094
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Chronic graft versus host disease (cGVHD) can affect people who had a hematopoietic stem cell transplant using donor cells. It is often fatal. It is usually treated with high doses of steroids. But that helps only about half the people in the long term. Researchers want to see if a drug called baricitinib can help people with cGVHD that has not responded to therapy. The drug inhibits the proteins involved in communication in the immune system. These proteins may play a role in cGVHD and other inflammatory diseases. Objectives: To test the safety and effectiveness of baricitinib in people with cGVHD that has not responded to therapy. Eligibility: Adults 18 and older with cGVHD that has not responded to therapy. Design: Participants will be screened with a medical history, physical exam, and blood and urine tests. They will have lung and heart tests and chest scans. Baseline visit: Participants will have: Medical history Physical exam Blood tests Tests for infectious diseases Skin, eye, and teeth evaluations Rehabilitation and occupational medicine evaluations Photos of any lesions Gynecology evaluation (females) The study will occur in 28-day cycles. Participants will take the study drug by mouth every day for 3 cycles. Some will take it for 3 or 6 more cycles. Participants will have a few visits during each cycle. They will repeat some previous tests. They may also have scans and questionnaires. Participants will have a visit when they stop taking the drug and another 3 months later. They will repeat a few study tests. They will have follow-up calls for 2 years.

Conditions

Chronic Graft vs Host Disease; Chronic Graft-Versus-Host Disease

Keywords

Murine Models; Rheumatoid Arthritis; Corticosteroids; Systemic Therapy; Inflammatory Cytokines

Outcome Measures

Primary Outcomes (3)

• Phase 1: Number of Participants With Dose-Limiting Toxicities (DLT)

  DLT is defined as any grade ≥3 non-hematologic or grade ≥4 hematologic adverse event, or hemoglobin \<6.5 g/dL, within 4 weeks of starting any dose level (1mg, 2mg, or 4 mg) except those that are clearly and incontrovertibly due to extraneous causes. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 3 is severe. Grade 4 is life-threatening.

  Starting at each dose level initiation, every 2 weeks up to the first 4 weeks of each dose

• Phase 2: Number of Participants With Any Serious and/or Non-Serious Grades 3, 4, and/or 5 Adverse Events Due to Drug

  Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 3 is severe. Grade 4 is life-threatening. And Grade 5 is death related to adverse event.

  every 4 weeks through study completion (up to 48 weeks)

• Phase 2: Overall Response at 24 Weeks

  Response was assessed by the National Institutes of Health (NIH) chronic graft-versus-host disease (cGVHD) response criteria. Complete Response (CR) is defined as resolution of all manifestations in each organ or site. Partial Response (PR) is defined as improvement at least 1 organ or site without progression in any other organ or site. Lack of Response including unchanged, mixed response, and disease progression. Mixed response is a CR or PR in at least 1 organ accompanied by progression in another organ. Unchanged is outcomes that do not meet the criteria for CR, PR, disease progression, or mixed response. Disease Progression is a change in the manifestations in each organ or site that does not meet the criteria for CR, PR, mixed response, unchanged or lack of response.

  24 weeks

Other Outcomes (1)

• Phase 1 and 2: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)

  Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days.

Study Arms (1)

Baricitinib

EXPERIMENTAL

Single arm, intra-patient dose escalation. Arm 1 (starting dose) -Baricitinib starting at a dose of 2mg daily for 12 weeks. If the response at 12 weeks is a complete response (CR) and there has not been a dose-limiting toxicity (DLT), the dose will remain at 2mg daily for an additional 12 weeks. Arm 2 (dose escalation) - If the response is a partial response (PR) or stable disease (from cohort 1), the dose will be increased to 4mg daily for an additional 12 weeks. If there has been a DLT within the first 4 weeks will have a dose reduction back to 2mg daily. Each participant is exposed to both dose levels (with the exception of participants who developed toxicity or progressive disease that caused them to discontinue study early before they were able to undergo the per-protocol dose escalation at 12 weeks).

Drug: Baricitinib

Interventions

Baricitinib DRUG

Cycle=28 days: Baricitinib: 1mg-4mg by mouth (PO) every day (QD)

Also known as: Olumiant

Baricitinib

Eligibility Criteria

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

You may qualify if:

• Moderate or severe Chronic Graft-Versus-Host Disease (cGVHD) (after allogeneic hematopoietic stem cell transplantation) diagnosed and staged per National Institutes of Health (NIH) criteria. Responses to Janus kinase (JAK) inhibitors have not been restricted to specific organs, so any organ involvement is eligible.
• Age greater than or equal to 18 years of age. Because inadequate dosing or adverse event data are currently available on the use of baricitinib in patients \<18 years of age, children are excluded from this study.
• Karnofsky performance score \>50%
• Chronic GVHD that did not respond to high-dose corticosteroids (prednisone at 1.0 mg/kg/day for at least 1 week or prednisone at 0.5 mg/kg/day or 1 mg/kg every other day for at least 4 weeks), or second-line therapy (any).
• If patient is taking systemic therapy for cGVHD at the time of enrollment, they must be on a stable or tapering doses in the preceding 4 weeks.
• Patients must have normal organ and marrow function as defined below:
• absolute neutrophil count greater than or equal to 1,000/mcL
• absolute lymphocyte count greater than or equal to 500/mcL
• platelets greater than or equal to 50,000/mcL
• hemoglobin greater than or equal to 9 g/dL
• total bilirubin less than or equal to 1.5 X institutional upper limit of normal, unless there is a known history of Gilbert's disease
• Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/Alanine aminotransferase (ALT) serum glutamic pyruvic transferase (SGPT) less than or equal to 3 X institutional upper limit of normal
• Creatinine \< 1.5 times the upper limit of normal, or:
• creatinine clearance greater than or equal to 50 mL/min/1.73 m\^2. Creatinine clearance should be calculated per institutional standard.
• Primary malignancy for which the patient received transplant has been stable for 3 months prior to enrollment on study.

You may not qualify if:

• Systemic immune suppression or systemic therapy for cGVHD started within preceding 4 weeks.
• Hypersensitivity to JAK inhibitors.
• Any serious medical condition within the previous 4 weeks which places the subject at an unacceptable risk if he or she were to participate in the study or confounds the ability to interpret data from the study, including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmias, acute kidney injury, or psychiatric illness/social situations that would limit compliance with study requirements.
• Uncontrolled infection, including active human immunodeficiency virus (HIV-1), Hepatitis B virus (HBV) and/or Hepatitis C virus (HCV) infection (positive HBV or HCV viral load in the setting of positive HBV core antibody or surface antibody or HCV antibody). History of HBV or HCV is allowed if there is no uncontrolled viral infection. Because the study agent may impact response to infections, patients with any active viral infection are excluded.
• Recurrent or progressive malignancy requiring anticancer treatment.
• Other cancer except that for which the transplant was done \<2 years before study entry, except non-melanoma skin cancer or carcinoma in situ of the uterine cervix or breast.
• Patients who are receiving any other investigational agents.
• NIH lung score 3.
• Pregnant women are excluded from this study because the teratogenic effects of baricitinib are unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with baricitinib, breastfeeding should be discontinued if the mother is treated with this agent.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome; Arthritis, Rheumatoid

Interventions

baricitinib

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases

Results Point of Contact

• Title: Dr. Steven Pavletic
• Organization: National Cancer Institute

pavletis@mail.nih.gov

240-760-6174

Study Officials

• Steven Z Pavletic, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 14, 2016
• First Posted: May 3, 2016
• Study Start: November 1, 2016
• Primary Completion: June 30, 2022
• Study Completion: May 30, 2024
• Last Updated: October 8, 2024
• Results First Posted: October 25, 2023

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

Locations

US (1)