Simvastatin in Waldenstrom's Macroglobulinemia

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%.

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