Recruiting
Phase 1
Phase 2

Leflunomide & Decitabine

Sponsor:

West Virginia University

Code:

NCT06923488

Conditions

Myelodysplastic Syndromes

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Leflunomide 10mg

Leflunomide 20mg

Decitabine

Study Details

Brief 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.

Conditions

Myelodysplastic Syndromes

Study ID

NCT06923488

Start date

Jul 15, 2025

Status verified date

Apr, 2026

Completion date

Oct, 2028

Anticipated

Primary completion date

Oct, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Patient has pathologically confirmed diagnosis of MDS
  • Patient has currently measurable disease meeting the following criteria:

  • Bone marrow biopsy with more than 5% blasts, AND
  • Absolute neutrophil count (ANC) less than 1,000/mcL, and/or platelet count less than 100,000/mcL and/or hemoglobin levels less than 10g/dL
  • Patient has received one prior treatment with a DNA methyltransferase inhibitor (DNMTi), also commonly called hypomethylating agent (HMA). Patients whose MDS has IDH1/IDH2 mutations should have received at least one available IDH1/IDH2 inhibitor
  • Patient has an Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
  • Patient has the following required baseline laboratory data (eligibility can be based on local lab results):

  • Total serum bilirubin level less than or equal to 2 times ULN
  • Estimated glomerular filtration rate (eGFR) greater than or equal to 45 mL/min/1.73 m2
  • Patients who have undergone alloHSCT are eligible if they are more than 28 days post stem cell infusion, have no evidence of GVHD > Grade 1, and are more than a week off all immunosuppressive therapy
  • If a female of childbearing potential, the patient has a negative serum or urine pregnancy test result within 7 days prior to the first dose of treatment. Women of non-childbearing potential are those who are postmenopausal greater than one year or who have had a bilateral tubal ligation or hysterectomy
  • If female of childbearing potential or a male patient, patient agrees to use an effective contraceptive method from the time of informed consent, during the course of the study, and for 3 months following the last dose of treatment
  • Patient understands and voluntarily signs the written informed consent prior to any study-specific procedures. A copy of the signed informed consent form will be retained by the treating institution

Exclusion Criteria:

  • Patients receiving any other investigational agents, or concurrent chemotherapy or immunotherapy
  • Patients with progression to acute myeloid leukemia
  • Patients with other malignancies requiring systemic chemotherapy, immunotherapy or targeted therapy in the last four weeks
  • Patients with uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms)
  • Patients with active or latent tuberculosis
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that per Principal Investigator's judgment would limit compliance with study requirements
  • Females who are pregnant or breast feeding
  • Any other clinical conditions that in the opinion of the investigator would make the subject unsuitable for the study

Study Design

Enrollment

26 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Leflunomide + Decitabine Treatment

Participants will receive combination treatment for 12 cycles consisting of 28 days. Utilizing a conventional 3+3 design, Decitabine will be at a dose of 20 mg/m2 and will be administered by intravenous infusion over 1 hour daily for 5 days each 28-day cycle. Leflunomide will have a dose escalation schedule starting at (Level +1) as follows:

Dose Escalation (Level -2): Leflunomide 10mg once daily by mouth x 14 days/cycle (Level -1): Leflunomide 10mg once daily by mouth x 21 days/cycle (Level +1): Leflunomide 20mg once daily by mouth x 14 days/cycle (Level +2): Leflunomide 20mg once daily by mouth x 21 days/cycle

Interventions

Leflunomide 10mg

Leflunomide 10mg tablet

Leflunomide 20mg

Leflunomide 20mg tablet

Decitabine

Decitabine dose of 20 mg/m2

Primary outcome measure

  • Percentage of incidences of regimen limiting toxicities (RLTs) [ Time Frame: Date of first treatment up to 13 months ]

Central Contacts and Locations

Central contacts

Konstantinos Sdrimas, MD

304-598-4520Konstantinos.sdrimas1@hsc.wvu.edu

Locations

West Virginia University Cancer Institute

Recruiting

Morgantown, West Virginia, United States, 26506

More Information

Sponsor

West Virginia University

Last update posted

Apr 23, 2026

Last verified

Apr, 2026

Keywords

  • relapsed or refractory

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by West Virginia University on 2026-04-23.