NCT05443425

Leflunomide in Combination With Steroids for the Treatment of Acute Graft-versus-Host Disease After Donor Stem Cell Transplant for Hematologic Malignancies

Pilot Trial of Leflunomide in Combination With Steroids for the Treatment of Acute Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies

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

Summary

This phase I trial tests the safety and side effects of leflunomide in combination with steroids in treating patients with acute graft versus host disease who have undergone done stem cell transplant for blood cancers (hematologic malignancies). Sometimes the transplanted cells from a donor can attack the body's normal cells (called graft-versus-host disease). Leflunomide and steroids are immunosuppressive drugs that work in different ways to lower the body's immune response so that the new donor immune cells do not attack the body's normal cells. Giving leflunomide in combination with steroids may help treat acute graft versus host disease in patients after stem cell transplant for hematologic malignancies.

Detailed description

PRIMARY OBJECTIVE: I. Assess the safety and tolerability of leflunomide administration in transplant patients with diagnosis of acute graft-versus-host disease (GvHD) requiring systemic therapy, by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration. SECONDARY OBJECTIVES: I. Obtain preliminary evidence of leflunomide activity against acute GvHD by estimating the overall response rate (ORR). II. Obtain estimates of total steroid dose and length of therapy (area under curve). III. Day +180 non-relapse mortality (NRM). IV. Overall survival (OS) and progression-free survival (PFS) at one-year. V. Rate and severity of infections during leflunomide administration. EXPLORATORY OBJECTIVES: I. Assess the clinical pharmacokinetics of teriflunomide (active metabolite of leflunomide). II. Assess the presence of and percentage of immune cell subsets (including but not limited to Th17 and regulatory T cells) in blood during leflunomide administration. III. Assess the changes in presence and levels of GvHD biomarkers and inflammatory cytokines in plasma during the course of treatment with leflunomide. IV. Obtain a preliminary estimate of gut microbiome diversity at baseline (preferably before leflunomide administration), and then on days +14, +28, and +56. OUTLINE: Patients receive steroid therapy at the discretion of the treating physician. Beginning within 3 days of starting steroids, patients receive leflunomide orally (PO) once daily (QD) on days 1-28 in the absence of disease progression or unacceptable toxicity. Patients who respond to leflunomide treatment will be tapered off from day 29 until day 56. After completion of study treatment, patients are followed up at 28 days, 56 days, 100 days, and 6 months from last dose of leflunomide.

Conditions

• Acute Graft Versus Host Disease
• Hematopoietic and Lymphoid System Neoplasm

Interventions

Type	Name	Description
DRUG	Cholestyramine	Given PO
DRUG	Leflunomide	Given PO
DRUG	Steroid Therapy	Given steroid therapy

Timeline

• Start date: 2023-06-16
• Primary completion: 2027-01-05
• Completion: 2027-01-05
• First posted: 2022-07-05
• Last updated: 2025-07-04

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study