Waldenstrom's Macroglobulinemia
Conditions
Keywords
simvastatin
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%.
Interventions
DRUGSimvastatin
Oral tablets taken daily
Sponsors
Dana-Farber Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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). \[Consensus panel criteria: Weber et al, 2003; Kimby et al, 2005\]. |
Countries
United States
Participant flow
Recruitment details
Outpatient Clinic at Dana Farber Cancer Institute
Pre-assignment details
Patients with progressive nonsymptomatic disease on watch and wait were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Simvastatin Single arm, phase II study. All 18 patients received study drug. | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | Simvastatin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Age, Continuous | 66 years STANDARD_DEVIATION 13 |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 17 |
| serious Total, serious adverse events | 0 / 17 |
Outcome results
Primary
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.
Time frame: 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).
Population: The analysis dataset is comprised of all evaluable patients. One patient was lost to follow-up within 3 weeks of enrollment and was unevaluable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Simvastatin | Objective Response Rate | 0.00 proportion of patients |
Primary
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). \[Consensus panel criteria: Weber et al, 2003; Kimby et al, 2005\].
Time frame: 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).
Population: The analysis dataset is comprised of all evaluable patients. One patient was lost to follow-up within 3 weeks of enrollment and was unevaluable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Simvastatin | Progression-Free Survival | 6 months |