NCT06923488

Leflunomide in Combination With Decitabine for Treatment of Relapsed or Refractory Myelodysplastic Syndromes

Phase I/II Study of Leflunomide in Combination With Decitabine for Treatment of Relapsed or Refractory (R/R) Myelodysplastic Syndromes (MDS)

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 26 (estimated)
• Sponsor: West Virginia University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this interventional clinical trial is to evaluate the safety and tolerability of leflunomide in combination with decitabine as treatment for patients with relapsed or refractory myelodysplastic syndromes (R/R MDS). The main question this study aims to answer are to evaluate and estimate the maximum tolerated doses and/or biologically active doses of the combination of leflunomide-decitabine in participants. Decitabine will be administered at a dose of 20 mg/m2 by continuous intravenous infusion over one hour repeated daily for 5 days with repeating cycle every 4 weeks. Leflunomide is administered orally at 10 to 20 mg once daily (without a loading dose) for 14 to 21 days, as part of a 28-day treatment cycle in adult subjects with R/R MDS. After 12 cycles (study duration) responding patients can continue progression with the assigned doses.

Detailed description

This is a phase I/II dose-escalation trial to estimate the activity of leflunomide in combination with decitabine for treatment of relapsed or refractory MDS. Leflunomide will be administered orally daily with decitabine IV for 5 days as part of a 28-day treatment cycle in adult subjects with R/R MDS. Patients who have been previously treated with decitabine will be eligible. The trial will consist of dose escalation to evaluate safety and tolerability of leflunomide in combination with decitabine. There will be no intra-patient dose escalation or reduction. In the event of an RLT, one or both drugs (leflunomide or decitabine) could be withheld at the discretion of the treating physician and on the basis of the expected adverse event. The period for determination of RLT will be from the first day of treatment until 30 days after receiving the first dose of leflunomide + decitabine. After 12 cycles (study duration) responding patients can continue progression with the assigned doses. Staging studies, including bone marrow biopsy and complete blood counts will be performed within 45 days prior to study enrollment and again within 30 days after completing Cycle 3, Cycle 6, and Cycle 12 and within 30 days of discontinuing study treatment. A repeat bone marrow biopsy will be performed at the end of the study (Cycle 12). Patients will be followed every 3 months for 2 years after completion of study. Study assessments will also include monitoring of all toxicities and adverse events. The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, will be used for grading adverse events and all toxicities

Conditions

• Myelodysplastic Syndromes

Interventions

Type	Name	Description
DRUG	Leflunomide 10mg	Leflunomide 10mg tablet
DRUG	Leflunomide 20mg	Leflunomide 20mg tablet
DRUG	Decitabine	Decitabine dose of 20 mg/m2

Timeline

• Start date: 2025-08-01
• Primary completion: 2027-10-01
• Completion: 2028-10-01
• First posted: 2025-04-11
• Last updated: 2025-07-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study