High-dose HMG-CoA Inhibitor Simvastatin Relapsed CLL

NCT00828282 | Completed Phase 1 DMC

• 1 other identifier: 08-LEUK-06-MCC
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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

Keywords

Chronic Lymphocytic Leukemia; Simvastatin; Zocor

Outcome Measures

Primary Outcomes (4)

• 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

  Begining of therapy and followed for 2 years after completing therapy

• Evaluate the feasibility of the proposed methods to determine the plasma and intra-cellular pharmacokinetics after high-dose simvastatin

  During therapy

• 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

  During therapy

• Evaluate the feasibility of proposed methods to identify changes in gene expression following high-dose simvastatin treatment

  Druing treatment

Study Arms (1)

1

EXPERIMENTAL

Drug: Simvastatin

Interventions

Simvastatin 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.

Also known as: Zocor

1

Eligibility Criteria

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• John Haslip: lead

Study Sites (1)

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Related Links

• Markey Cancer Center Blood and Marrow Transplant Study Search

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• John Hayslip, MD, MSCR

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Clinical Research and Data Management Shared Resource Facility

Study Record Dates

• First Submitted: January 22, 2009
• First Posted: January 23, 2009
• Study Start: March 1, 2009
• Primary Completion: January 1, 2011
• Study Completion: April 1, 2014
• Last Updated: May 26, 2014

Record last verified: 2014-05

Locations

US (1)