Leflunomide in Treating Patients With Relapsed or Refractory Multiple Myeloma

Inclusion Criteria

• •All subjects must have the ability to understand and the willingness to sign a written informed consent
• •Patients must have a life expectancy of \> 3 months
• •Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• •Patients must have a diagnosis of multiple myeloma
• •Serum M-protein \>= 0.5 g/dL
• •Urine M-protein \>= 200 mg/24 hr
• •Serum free light chain \>=10 mg/dL provided the free light chain (FLC) ratio is abnormal
• •10% plasma cells in bone marrow
• •Patients must be relapsed or are refractory to at least 3 prior lines of therapy, including both a proteasome inhibitor an immunomodulatory drug (IMiD), and for whom a transplant is not recommended (induction therapy and stem cell transplant +/- maintenance will be considered as one regimen)
• •At least 2 weeks from prior therapy to time of start of treatment; prior therapy includes steroids (except prednisone or equivalent - up to 10 mg per day is allowed)
• •Platelet count \>= 50,000/uL; platelet transfusions are not allowed within 14 days of platelet assessment
• •Absolute neutrophil count (ANC) \>= 1000/mm\^3; growth factor is not permitted within 14 days of neutrophil assessment
• •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.0 x upper limit of normal (ULN)
• •Total Bilirubin \< 1.5 x ULN
• •Calculated creatinine clearance (CrCl) \>= 30 mL/min per 24 hour urine collection or the Cockcroft-Gault formula
• •Negative serum or urine beta-human chorionic gonadotropin (B-HCG) test (female patient of childbearing potential\* only), to be performed locally within the screening period
• •Negative for tuberculosis antigen (e.g. T-Spot test)
• •Negative for hepatitis A, B, or C infection
• •Adequate pulmonary function as defined by forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO) \>= 50% of predicted by pulmonary function testing
• •Agreement by females of childbearing potential\* and sexually active males to use an effective method of contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for three months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately \* A female of childbearing potential is defined as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months