Simvastatin in Waldenstrom's Macroglobulinemia

Study Overview
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Brief Summary
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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.

Detailed Description
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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%.

Official Title
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Phase II Study of Simvastatin in Waldenstrom's Macroglobulinemia

Conditions
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Waldenstrom's Macroglobulinemia

Intervention / Treatment
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* Drug: Simvastatin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Simvastatin<br>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. | Drug: Simvastatin<br>* Oral tablets taken daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Objective response is defined as achieving partial response or better on therapy based on the Consensus Panel Recommendations from the 2nd and 3rd International Workshop on WM [Weber et al, 2003; Kimby et al, 2005]. Complete Response (CR): Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. Partial Response (PR): a >=50% reduction from baseline in the SM IgM concentration. Minor Response (MR): >=25%, but a <50% reduction of SM IgM from baseline. | Assessed at month 1 and 3 and thereafter every 3 months while on therapy. Median duration on treatment was 6 months (range 1-24 months). | 
| Progression-Free Survival | Progression-free survival is the defined as the time from study entry to disease progression (PD) or death based on Kaplan-Meier estimates. Patients alibe without PD are censored at the date of last disease evaluation. PD is defined as a greater than 25% increase in serum IgM monoclonal protein levels from the lowest attained response value as determined by serum electrophoresis, confirmed by at least one other investigation, or progression of clinically significant disease related symptom(s). [Consensus panel criteria: Weber et al, 2003; Kimby et al, 2005]. | Assessed at month 1 and 3 and thereafter every 3 months while on therapy; Assessed every 6 months for up to 2 years of follow-up. Median follow-up in this study cohort was 6 months (range 2-18 months). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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simvastatin