- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00828282
High-dose HMG-CoA Inhibitor Simvastatin Relapsed CLL
May 23, 2014 updated by: John Haslip
High-dose HMG-CoA Inhibitor Simvastatin for Patients With Relapsed CLL: Pilot Trial and Pharmacokinetic-pharmacodynamic Studies
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.
Study Overview
Study Type
Interventional
Enrollment (Actual)
3
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Kentucky
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Lexington, Kentucky, United States, 40536
- University of Kentucky
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Eligibility Criteria:
- Patients must have histologically or cytologically confirmed chronic lymphocytic leukemia (CLL). Criteria for diagnosis are as per the WHO classification of hematologic tumors (Jaffe 2001). As per the 1996 NCI guidelines for CLL "[second-line or later] treatment of CLL is generally palliative in intent; therefore, patients who have relapsed may be followed without therapy until they experience disease-related symptoms or progressive disease, with deterioration of blood counts, discomfort from lymphadenopathy or hepatosplenomegaly, recurrent infections, or associated autoimmune disorders" (Cheson 1996).
- Age >18 years. Because no dosing or adverse event data are currently available on the use of high-dose simvastatin in patients <18 years of age, children are excluded from this study.
- 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.
Exclusion Criteria:
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: 1
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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 Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
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Begining of therapy and followed for 2 years after completing therapy
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Evaluate the feasibility of the proposed methods to determine the plasma and intra-cellular pharmacokinetics after high-dose simvastatin
Time Frame: During therapy
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During therapy
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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
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During therapy
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Evaluate the feasibility of proposed methods to identify changes in gene expression following high-dose simvastatin treatment
Time Frame: Druing treatment
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Druing treatment
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: John Hayslip, MD, MSCR, University of Kentucky
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2009
Primary Completion (Actual)
January 1, 2011
Study Completion (Actual)
April 1, 2014
Study Registration Dates
First Submitted
January 22, 2009
First Submitted That Met QC Criteria
January 22, 2009
First Posted (Estimate)
January 23, 2009
Study Record Updates
Last Update Posted (Estimate)
May 26, 2014
Last Update Submitted That Met QC Criteria
May 23, 2014
Last Verified
May 1, 2014
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Leukemia
- Leukemia, B-Cell
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Simvastatin
Other Study ID Numbers
- 08-LEUK-06-MCC
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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