Simvastatin in Waldenstrom's Macroglobulinemia

Phase 2

Terminated

Conditions: Waldenstrom's Macroglobulinemia

Interventions: Drug: Simvastatin

Registration Number: NCT00575965

Lead Sponsor: Dana-Farber Cancer Institute

Brief Summary: 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: 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%.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 18

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Simvastatin	Simvastatin	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.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival	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).	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). \[Consensus panel criteria: Weber et al, 2003; Kimby et al, 2005\].
Objective Response Rate	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).	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.

Secondary Outcome Measures