Mercaptopurine for the Treatment of Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC), Uterine/Cutaneous Leiomyomas, and Kidney Cancer

PRIMARY OBJECTIVE: I. To identify the safety, side effects, and best dose of mercaptopurine (6-MP). SECONDARY OBJECTIVES: I. To assess clinical activity in treating metastatic fumarate hydratase (FH) Deficient Kidney Cancer. II. To assess how treatment impacts uterine fibroid clinical symptoms. III. To determine the change in menstrual bleeding. IV. To evaluate changes in pain due to leiomyomas. V. To evaluate the overall improvement in leiomyoma symptoms. EXPLORATORY OBJECTIVES: I. Associate changes in serum thiopurine metabolites (6-methylmercaptopurine \[6-MMP\] and 6-thioguanine \[6-TG\]) with efficacy endpoints for kidney cancer, cutaneous leiomyoma, and uterine fibroids. II. Generate in vitro and in vivo models of cutaneous leiomyomas and kidney cancer that may be useful to predict clinical activity to treatment with 6-MP or purine restriction. III. Bank clinical specimens (urine, tissue, blood) and tissue for future HLRCC research. OUTLINE: This is a phase I dose-escalation study followed by a phase II study. Patients receive 6-MP orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days for up to 26 cycles/2 years (for kidney cohort) or up to 13 cycles/1 year (for skin or uterine cohorts) in the absence of disease progression or unacceptable toxicity. Patients may also undergo computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study (kidney and uterine cohorts only), tumor biopsy on study (kidney cohort only), skin biopsy on study (skin cohort only), and blood sample collection throughout the study (all cohorts). After completion of study treatment, patients are followed up within 45 days and then every 12 months for 2 years.