High-dose HMG-CoA Inhibitor Simvastatin Relapsed CLL

NCT ID: NCT00828282

Last Updated: 2014-05-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-31
• Study Completion Date: 2014-04-30

Brief Summary

The primary aim of this trial is to generate a preliminary analysis of this novel therapeutic approach and laboratory studies for patients with recurrent or refractory CLL. Further, this pilot trial will demonstrate the feasibility of the translational science methods proposed for this new collaboration of investigators. The investigators hypothesize that patients with relapsed CLL are recruitable to this study, that the methods for measuring simvastatin concentration and target protein translation are feasible, and that the investigators can efficiently apply the laboratory research methods to patient blood samples before and after patients have taken the study medication.

Conditions

Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Group Type: EXPERIMENTAL

Simvastatin

Intervention Type: DRUG

Treatment will be administered on an outpatient basis. Subjects will be given 7.5 mg/kg twice daily of Simvastatin for 7 days on a 21-day cycle with a goal of 6 cycles.

Interventions

Simvastatin

Treatment will be administered on an outpatient basis. Subjects will be given 7.5 mg/kg twice daily of Simvastatin for 7 days on a 21-day cycle with a goal of 6 cycles.

Intervention Type: DRUG

Other Intervention Names

Zocor

Eligibility Criteria

Exclusion Criteria

• Life expectancy of greater than 6 months.
• ECOG performance status #2 or better.
• Patients must have normal organ and marrow function as defined below:

• total bilirubin within normal institutional limits unless resulting from documented hemolysis
• AST(SGOT)/ALT(SGPT) ≤1.5 X institutional upper limit of normal
• creatinine ≤ 1.5 institutional upper limit of normal OR
• creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
• Creatine phosphokinase ≤ 1.5 institutional upper limit of normal
• Patients with active infections requiring systemic antibiotics should be excluded until resolution of infection
• The effects simvastatin on the developing human fetus at the studied therapeutic dose are unknown. For this reason and because HMG-CoA reductase inhibitors may be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document.

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Patients may not be receiving any other investigational agents.
• Patients with known brain or nervous system disease should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to simvastatin.
• Patients receiving any medications or substances that are inhibitors or inducers of CYP3A4 are ineligible. Lists including medications and substances known or with the potential to interact with the CYP3A4 isoenzymes are provided in the appendix.
• Patients may not take other anti-cholesterol treatments during this study. Patients who were previously taking anti-cholesterol treatment prior to study entry must be off the anti-cholesterol medications for 14 days before enrolling on this trial.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, diarrhea, myopathy, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because HMG-CoA reductase inhibitors are a drug class with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with simvastatin, breastfeeding should be discontinued if the mother is treated with simvastatin.
• HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with simvastatin.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

John Haslip

OTHER

Sponsor Role: lead

Responsible Party

John Haslip

Director, Clinical Research and Data Management Shared Resource Facility

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

John Hayslip, MD, MSCR

Role: PRINCIPAL_INVESTIGATOR

University of Kentucky

Locations

University of Kentucky

Lexington, Kentucky, United States

Countries

United States

Related Links

http://markey.uky.edu/studysearch/default.aspx?site=Blood%20and%20Marrow%20Transplant

Markey Cancer Center Blood and Marrow Transplant Study Search

Other Identifiers

08-LEUK-06-MCC

Identifier Type: -

Identifier Source: org_study_id