PRIMARY OBJECTIVE:
I. To estimate the anti-myeloma activity of leflunomide, when given as a single agent, as assessed by 6-month progression-free response rate based on International Myeloma Working Group (IMWG) criteria.
SECONDARY OBJECTIVES:
I. To evaluate the safety and tolerability of single agent leflunomide. II. To summarize and assess toxicities by type, frequency, severity, attribution, time course and duration.
III. To estimate overall and progression-free survival probabilities. IV. To estimate response rate and duration of response. V. To describe the impact of treatment on quality of life, as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQC30) Score version (v)3.0.
EXPLORATORY OBJECTIVES:
I. To characterize the molecular evolution of the tumor cells. II. To evaluate whether specific genetic subtypes respond differently to leflunomide.
III. To evaluate the role of immune cells in the progression of smoldering multiple myeloma (SMM).
IV. To evaluate the role of leflunomide in modulating the immune system. V. To examine the relationship between immunological changes and disease progression.
OUTLINEPatients receive leflunomide orally (PO) once daily (QD). Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After the completion of study treatment, patients are followed up at 30 days, every 28 days until an alternative myeloma therapy has commenced or until disease progression, and then up to 6 months.
