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Simvastatin in Waldenstrom's Macroglobulinemia

Primary Purpose

Waldenstrom's Macroglobulinemia

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Simvastatin
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Waldenstrom's Macroglobulinemia focused on measuring simvastatin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Simvastatin

Arm 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.

Outcomes

Primary Outcome Measures

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.
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].

Secondary Outcome Measures

Full Information

First Posted
December 16, 2007
Last Updated
November 11, 2015
Sponsor
Dana-Farber Cancer Institute
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1. Study Identification

Unique Protocol Identification Number
NCT00575965
Brief Title
Simvastatin in Waldenstrom's Macroglobulinemia
Official Title
Phase II Study of Simvastatin in Waldenstrom's Macroglobulinemia
Study Type
Interventional

2. Study Status

Record Verification Date
November 2015
Overall Recruitment Status
Terminated
Why Stopped
Slow accrual led to early study termination.
Study Start Date
November 2007 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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%.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Waldenstrom's Macroglobulinemia
Keywords
simvastatin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Simvastatin
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Simvastatin
Intervention Description
Oral tablets taken daily
Primary Outcome Measure Information:
Title
Objective Response Rate
Description
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).
Title
Progression-Free Survival
Description
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).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven Treon, MD, PhD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

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Simvastatin in Waldenstrom's Macroglobulinemia

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