High-dose HMG-CoA Inhibitor Simvastatin Relapsed CLL
This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
John Haslip, University of Kentucky
First received: January 22, 2009
Last updated: November 14, 2013
Last verified: November 2013
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.
Chronic Lymphocytic Leukemia
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||High-dose HMG-CoA Inhibitor Simvastatin for Patients With Relapsed CLL: Pilot Trial and Pharmacokinetic-pharmacodynamic Studies
Primary Outcome Measures:
- Evaluate the feasibility of investigators to recruit, retain & evaluate responses in a pilot study of participants with relapsed/refractory CLL treated with 7.5 mg/kg of simvastatin taken orally twice daily on days 1-7 of every 21 day cycles for 6 cycles [ Time Frame: Begining of therapy and followed for 2 years after completing therapy ] [ Designated as safety issue: Yes ]
- Evaluate the feasibility of the proposed methods to determine the plasma and intra-cellular pharmacokinetics after high-dose simvastatin [ Time Frame: During therapy ] [ Designated as safety issue: No ]
- Evaluate the feasibility of proposed methods to determine if high-dose simvastatin treatment affects the prenylation dependent cellular localization of Rho GTPase proteins and to assess the apoptotic index of CLL cells from treated participants [ Time Frame: During therapy ] [ Designated as safety issue: No ]
- Evaluate the feasibility of proposed methods to identify changes in gene expression following high-dose simvastatin treatment [ Time Frame: Druing treatment ] [ Designated as safety issue: No ]
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Primary Completion Date:
||January 2011 (Final data collection date for primary outcome measure)
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.
Other Name: Zocor
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00828282
|University of Kentucky
|Lexington, Kentucky, United States, 40536 |
||John Hayslip, MD, MSCR
||University of Kentucky
No publications provided
||John Haslip, Director, Clinical Research and Data Management Shared Resource Facility, University of Kentucky
History of Changes
|Other Study ID Numbers:
|Study First Received:
||January 22, 2009
||November 14, 2013
||United States: Institutional Review Board
Keywords provided by University of Kentucky:
Chronic Lymphocytic Leukemia
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on December 10, 2013
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors