Simvastatin in Waldenstrom's Macroglobulinemia

Dana-Farber Cancer Institute

Status and phase: Terminated; Phase 2

Conditions: Waldenstrom's Macroglobulinemia

Treatments: Drug: Simvastatin

Study type: Interventional

Funder types: Other

Identifiers

NCT00575965

07-175

Details and patient eligibility

About

This research study seeks to find new ways to treat people with Waldenstrom's Macroglobulinemia (WM). The study is for participants with slow growing WM who otherwise might not need therapy for at least 3-6 months. Simvastatin is a drug approved by the FDA for lowering cholesterol. In test tube studies the study drug appears to have direct anti-cancer effect against WM tumor cells and mast cells.

Full description

OBJECTIVES:

To define objective response, time to progression and safety of Simvastatin in Waldenström's Macroglobulinemia.

STATISTICAL DESIGN:

For this phase II study, a single-stage design is used to evaluate the efficacy of Simvastatin. With a target enrollment of 30 participants, the 95% exact confidence bounds surrounding the response estimate will be no wider than +/- 19%.

Enrollment: 18 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 18 years of age or older
• Clinicopathological diagnosis of Waldenstrom's macroglobulinemia
• Measurable disease
• Slowly progressing disease not requiring therapy for at least 3-6 months and who do not meet consensus panel criteria for initiation of therapy
• ECOG Performance status of 0 or 1
• Adequate organ function as defined in the protocol
• Patients should agree to avoid grapefruit juice which is a major inhibitor of CYP 3A4

Exclusion criteria

• Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study, or those who have not recovered from adverse events due to agents administered more than four weeks earlier
• Patients who have had rituximab within 3 months prior to entering the study
• Patients who have taken any Statin in the past
• Patients who take cyclosporin, danazol, or gemfibrozil will be excluded
• Prior history of rhabdomyolysis
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with the study requirements
• Pregnant or breastfeeding women
• HIV-positive
• Patients who take verapamil will be excluded
• Patients with active or history of liver disease
• Patients who consume more than three alcoholic beverages per day

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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18 participants in 1 patient group

Simvastatin

Experimental group

Description:

Simvastatin at 20 mg daily for the first week, then dose escalated weekly by 20 mg a day to a maximum of 80 mg daily by week 4. Patients were maintained on therapy until progression.

Treatment:

Drug: Simvastatin