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