NCT04212416

Leflunomide in Treating Patients With Steroid Dependent Chronic Graft Versus Host Disease

A Safety and Feasibility Trial of Leflunomide in Patients With Steroid Dependent Chronic Graft-Versus-Host Disease

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects of leflunomide in treating patients with steroid dependent chronic graft versus host disease (cGVHD). cGVHD is a common complication of bone marrow transplant. GVHD occurs when immune cells transplanted from a donor (the graft) recognize the transplant recipient (the host) as foreign, and cause damage to the skin, gastrointestinal tract or other organs. Steroids are the first line of therapy and benefits are seen in about one-third of patients with cGVHD. Prolonged use of steroids is associated with multiple complications. Leflunomide may decrease the body's immune response and reduce inflammation associated with cGVHD.

Detailed description

PRIMARY OBJECTIVE: I. Evaluate safety and tolerability of leflunomide in hematopoietic cell transplant (HCT) patients with steroid dependent chronic GvHD (cGvHD). SECONDARY OBJECTIVES: I. Characterize the toxicity profile of leflunomide in patients with steroid dependent cGVHD. II. Obtain preliminary evidence of leflunomide activity against GVHD by estimating the response rate (as defined by 2014 National Institutes of Health \[NIH\] consensus development project on clinical trials in cGVHD) in an expansion cohort of 12 patients with steroid dependent cGVHD. III. Evaluate changes in cGVHD severity using physician-reported cGVHD activity assessment form. IV. Evaluate changes in symptom activity using cGVHD activity assessment patient self-report. V. Evaluate failure-free survival and GVHD free survival. VI. Evaluate changes in steroid doses while on therapy. VII. Evaluate rate of infectious complications during leflunomide administration. EXPLORATORY OBJECTIVES: I. Assess the presence and percentage of immune cell subsets (including but not limited to Th17 and Treg cells) in whole blood after leflunomide administration. II. Assess the changes in the presence and levels of GVHD inflammatory biomarkers and cytokines (including but not limited to IL-17A, IL-21, and IL-2) in plasma after leflunomide administration. III. Assess the plasma pharmacokinetics of teriflunomide (active metabolite of leflunomide). OUTLINE: Patients receive leflunomide orally (PO) once daily (QD) for days 1-28. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may optionally continue leflunomide for an additional 6 cycles as long as response or stable disease is maintained. After completion of study treatment, patients are followed up at 30 days, and then periodically thereafter.

Conditions

• Chronic Graft Versus Host Disease
• Steroid Refractory Graft Versus Host Disease

Interventions

Type	Name	Description
DRUG	Leflunomide	Given PO

Timeline

• Start date: 2020-05-12
• Primary completion: 2026-06-22
• Completion: 2026-06-22
• First posted: 2019-12-27
• Last updated: 2025-07-04

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study