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

Prior treatment

• Patients receiving any other investigational agents, or concurrent chemotherapy or immunotherapy

Other illness

• 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
• Any other clinical conditions that in the opinion of the investigator would make the subject unsuitable for the study

Other

• Patients with progression to acute myeloid leukemia
• Females who are pregnant or breast feeding

• 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