Simvastatin in Waldenstrom's Macroglobulinemia

NCT00575965 | Terminated Phase 2 Results DMC

• 1 other identifier: 07-175
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Waldenstrom's Macroglobulinemia

Keywords

simvastatin

Outcome Measures

Primary Outcomes (2)

• 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).

Study Arms (1)

Simvastatin

EXPERIMENTAL

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

Interventions

Simvastatin DRUG

Oral tablets taken daily

Simvastatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Limitations and Caveats

Slow accrual led to early study termination.

Results Point of Contact

• Title: Steven P. Treon MD, PhD
• Organization: Dana Farber Cancer Institute

steven_treon@dfci.harvard.edu

617 632 5880

Study Officials

• Steven Treon, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Bing Center

Study Record Dates

• First Submitted: December 16, 2007
• First Posted: December 18, 2007
• Study Start: November 1, 2007
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: December 16, 2015
• Results First Posted: December 16, 2015

Record last verified: 2015-11

Locations

US (1)