This phase I/II trial studies the side effects and best dose of mercaptopurine, and to see how well it works in treating patients with hereditary leiomyomatosis and renal cell carcinoma (HLRCC). HLRCC is a rare inherited disorder that increases the risk of developing benign (not cancer) tumors of the skin and the uterus (leiomyomas) and malignant (cancer) tumors of the uterus (leiomyosarcoma) and the kidney. Mercaptopurine is in a class of medications called purine antagonists. It works by stopping the growth of cancer cells.
Eligibility criteria
This trial does not accept healthy volunteers
Qualifiers
Age ≥ 18
a) Pathogenic/likely pathogenic OR
b) variants of unknown significance (VUS) with immunohistochemical staining showing loss of FH or high 2-SC expression in tumor tissue
Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1
Disqualifiers
Absolute contraindication to the use of contrast-enhanced imaging for efficacy assessment. If moderate allergy, patients could be allowed if pre-medication can be given to limit adverse reactions. (*Not relevant for skin-only cohort)
Presence of untreated brain metastases. Treated brain metastases must be stable for 4 weeks after treatment, have no clinical symptoms, and not be on corticosteroids > 10 mg/day of prednisone-equivalent > 2 weeks prior to treatment. Patients with known leptomeningeal metastases are excluded
Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (> 10 mg daily prednisone equivalent) or immunosuppressive medications within 14 days prior to first dose of study drug. An exception is allowed for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
History of myocarditis or congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), as well as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 6 months prior to study entry
Trial design
Design model
Single group
Treatments tested in this trial
Biopsy Procedure
Procedure/Surgery
Undergo tumor biopsy
Biospecimen Collection
Procedure/Surgery
Undergo collection of blood
Computed Tomography
Procedure/Surgery
Undergo CT
Magnetic Resonance Imaging
Procedure/Surgery
Undergo MRI
Mercaptopurine
Drug
Given PO
Questionnaire Administration
Other intervention
Ancillary studies
Skin Biopsy
Procedure/Surgery
Undergo skin biopsy
Treatment groups
18 Participants
are divided into 1 treatment group
Group A: Treatment (6-MP)Experimental treatment 7 interventions
Trial outcomes
Primary outcomes
1
Maximum tolerated dose (MTD)
Will be determined using Common Terminology Criteria for Adverse Events version 5.0 grading.
Time frame
Up to cycle 2 (Cycles = 28 days)
Secondary outcomes
1
Best overall response (Kidney Cancer Cohort)
Will be assessed per Response Evaluation Criteria in Solid Tumors. A descriptive summary will report the proportion of patients with complete response, partial response, stable disease, or progressive disease. Patients who are unevaluable will be summarized separately.
Time frame
Up to 2 years after completion of study treatment
2
Progression-free survival (PFS) (Kidney Cancer Cohort)
Kaplan-Meier survival curves will be generated to estimate the distribution of PFS, including median survival and confidence intervals. Landmark analyses will be conducted at 1-year and 2-year time points to estimate the proportion of patients remaining progression-free at these intervals, providing both longitudinal and milestone-based insights into disease control.
Time frame
From study enrollment to documented disease progression or death from any cause, assessed up to 2 years after completion of study treatment
3
Tumor volume changes (Uterine Fibroids Cohort)
Will be assessed via pelvic magnetic resonance imaging. A descriptive summary will report maximal volume reduction from baseline, including the proportion of patients achieving partial or complete response, stable disease, or progression, based on predefined thresholds. Mean and median volume changes will be calculated, and overall response rates will be summarized.
Time frame
Up to 1 year
4
Changes in Pictorial Blood Loss Assessment Chart (PBAC) scores (Uterine Fibroids Cohort)
Will be summarized from baseline to follow-up. Response will be defined as a ≥ 50% reduction in PBAC score. The proportion of responders and non-responders will be reported, along with changes in mean and median scores.
Time frame
Baseline up to 1 year
Other outcomes
Sponsors and contacts
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