Feasibility Study of Simvastatin in Hodgkin's Lymphoma Survivors

Sponsor
Columbia University (Other)
Overall Status
Terminated
CT.gov ID
NCT00746603
Collaborator
Children's Hospital of Philadelphia (Other)
3
1
1
18
0.2

Study Details

Study Description

Brief Summary

Lay abstract: Study Purpose With contemporary combined modality therapy the expected longterm survival of children and adolescents with Hodgkin's disease (HD) is exceedingly high. Thus, the emphasis for future therapeutic interventions must include attention to the late effects of therapy. The development of cardiovascular disease as a late effect of radiation therapy has been well described and documented. Our recent pilot study of child and young adult HD survivors revealed significant subclinical atherosclerosis as evidenced by increased Carotid Artery Intima Media Thickness (CIMT) compared to controls. The higher CIMT values were positively associated with increasing age, total cholesterol, LDLcholesterol and diastolic BP. This finding was present in children and young adults who had received no or low dose radiation suggesting that chemotherapy or the disease process itself contributes to the development of atherosclerosis and risk for cardiovascular disease. Numerous studies have shown HMG CoA reductase inhibitors ("statins") to be effective in reducing the progression of atherosclerosis in adults. These agents have been studied in children and young adults for over a decade.

The primary aim of this study is:

To obtain pilot safety data on the use of simvastatin in young adults treated for HD.

The secondary aims of this study are:

To obtain pilot data on the effect of simvastatin on subclinical carotid artery atherosclerosis as measured by Carotid Artery IMT in young adults treated for HD.

To obtain pilot data on the effect of simvastatin on markers of inflammation measured in the serum of young adults treated for HD.

To obtain pilot data to serve as the basis for the development of a multicenter randomized study for the use of simvastatin in survivors of HD.

Condition or Disease Intervention/Treatment Phase
N/A

Detailed Description

With contemporary combined modality therapy the expected longterm survival of children and adolescents with Hodgkin's disease (HD) is exceedingly high. Thus, the emphasis for future therapeutic interventions must include attention to the late effects of therapy. The development of cardiovascular disease as a late effect of radiation therapy has been well described and documented. Our recent pilot study of child and young adult HD survivors revealed significant subclinical atherosclerosis as evidenced by increased Carotid Artery Intima Media Thickness (CIMT) compared to controls. The higher CIMT values were positively associated with increasing age, total cholesterol, LDLcholesterol and diastolic BP. This finding was present in children and young adults who had received no or low dose radiation suggesting that chemotherapy or the disease process itself contributes to the development of atherosclerosis and risk for cardiovascular disease. Numerous studies have shown HMG CoA reductase inhibitors ("statins") to be effective in reducing the progression of atherosclerosis in adults. These agents have been studied in children and young adults for over a decade.

The primary aim of this study is:

To obtain pilot safety data on the use of simvastatin in young adults treated for HD.

The secondary aims of this study are:

To obtain pilot data on the effect of simvastatin on subclinical carotid artery atherosclerosis as measured by Carotid Artery IMT in young adults treated for HD.

To obtain pilot data on the effect of simvastatin on markers of inflammation measured in the serum of young adults treated for HD.

To obtain pilot data to serve as the basis for the development of a multicenter randomized study for the use of simvastatin in survivors of HD.

We will do this by enrolling patients diagnosed with HD and evaluating the safety of simvastatin as evidenced by laboratory measures

Study Design

Study Type:
Interventional
Actual Enrollment :
3 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
A Feasibility Study to Evaluate the Safety of Simvastatin in Young Adults Treated for Hodgkin's Disease
Study Start Date :
Jan 1, 2008
Actual Primary Completion Date :
Jul 1, 2009
Actual Study Completion Date :
Jul 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Experimental: A Intervention Arm

Escalating dose of simvastatin in subjects who are survivors of Hodgkin Lymphoma

Drug: Simvastatin
All patients will start at 10mg of simvastatin, and then, based on results of interim evaluation escalated to 20mg and then 40. Patients will stay on maximally tolerated dose of drug until the end of the study at 26 weeks.
Other Names:
  • Zocor
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participants Experiencing Grade 3 or Greater Muscle Toxicity [Up to 26 weeks]

      Number of participants experiencing grade 3 or greater muscle toxicity as evaluated by creatinine kinase laboratory tests.

    2. Number of Participants Experiencing Grade 3 or Higher Liver Toxicity [Up to 26 Weeks]

      Number of participants experiencing grade 3 or higher liver toxicity as determined by liver function laboratory tests.

    3. Change in Carotid Intima-media Thickness Test (CIMT) [Up to 26 Weeks]

      A change in CIMT measurements ( measured in millimeters (mm)) will be performed.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 35 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • At least three years from completion of treatment for Hodgkin's Disease

    • Age 18- 35

    • Ability to complete self report questionnaires in either English or Spanish

    • Willingness of patient, or parent/guardian if patient less than 18 years of age to sign consent to participate in study

    • Willingness of patient to sign assent if greater than 7 years of age and less than 18 years

    Exclusion Criteria:
    • Pregnant or breast feeding

    • Tanner Stage 1

    • Currently taking cyclosporine, niacin, antiretrovirals, macrolide antibiotic, azole antifungal

    • Liver enzymes greater than 1.5 times the upper level of normal

    • Creatine Kinase greater than 2 times the upper level of normal

    • Use of estrogen containing contraceptive

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Columbia Univeristy Medical Center New York New York United States 10032

    Sponsors and Collaborators

    • Columbia University
    • Children's Hospital of Philadelphia

    Investigators

    • Principal Investigator: Jennifer Levine, MD, Columbia Univeristy Medical Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Columbia University
    ClinicalTrials.gov Identifier:
    NCT00746603
    Other Study ID Numbers:
    • AAAB4447
    First Posted:
    Sep 4, 2008
    Last Update Posted:
    Mar 2, 2021
    Last Verified:
    Feb 1, 2021
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details recruitment occurred in the late effects clinic
    Pre-assignment Detail
    Arm/Group Title Simvastatin
    Arm/Group Description Escalating dose of simvastatin Simvastatin: All patients will start at 10mg of simvastatin, and then, based on results of interim evaluation escalated to 20mg and then 40. Patients will stay on maximally tolerated dose of drug until the end of the study at 26 weeks.
    Period Title: Overall Study
    STARTED 3
    COMPLETED 3
    NOT COMPLETED 0

    Baseline Characteristics

    Arm/Group Title Simvastatin
    Arm/Group Description Escalating dose of simvastatin Simvastatin: All patients will start at 10mg of simvastatin, and then, based on results of interim evaluation escalated to 20mg and then 40. Patients will stay on maximally tolerated dose of drug until the end of the study at 26 weeks.
    Overall Participants 3
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    3
    100%
    >=65 years
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    1
    33.3%
    Male
    2
    66.7%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    33.3%
    Not Hispanic or Latino
    0
    0%
    Unknown or Not Reported
    2
    66.7%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    0
    0%
    White
    0
    0%
    More than one race
    0
    0%
    Unknown or Not Reported
    3
    100%
    Region of Enrollment (participants) [Number]
    United States
    3
    100%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants Experiencing Grade 3 or Greater Muscle Toxicity
    Description Number of participants experiencing grade 3 or greater muscle toxicity as evaluated by creatinine kinase laboratory tests.
    Time Frame Up to 26 weeks

    Outcome Measure Data

    Analysis Population Description
    The study terminated in 2009 due to poor enrollment. The principal investigator (PI) and study team are no longer at the institution and the PI has confirmed that the data no longer exists. There are no data to report.
    Arm/Group Title Simvastatin
    Arm/Group Description Escalating dose of simvastatin Simvastatin: All patients will start at 10mg of simvastatin, and then, based on results of interim evaluation escalated to 20mg and then 40. Patients will stay on maximally tolerated dose of drug until the end of the study at 26 weeks.
    Measure Participants 0
    2. Primary Outcome
    Title Number of Participants Experiencing Grade 3 or Higher Liver Toxicity
    Description Number of participants experiencing grade 3 or higher liver toxicity as determined by liver function laboratory tests.
    Time Frame Up to 26 Weeks

    Outcome Measure Data

    Analysis Population Description
    The study terminated in 2009 due to poor enrollment. The principal investigator (PI) and study team are no longer at the institution and the PI has confirmed that the data no longer exists. There are no data to report.
    Arm/Group Title Simvastatin
    Arm/Group Description Escalating dose of simvastatin Simvastatin: All patients will start at 10mg of simvastatin, and then, based on results of interim evaluation escalated to 20mg and then 40. Patients will stay on maximally tolerated dose of drug until the end of the study at 26 weeks.
    Measure Participants 0
    3. Primary Outcome
    Title Change in Carotid Intima-media Thickness Test (CIMT)
    Description A change in CIMT measurements ( measured in millimeters (mm)) will be performed.
    Time Frame Up to 26 Weeks

    Outcome Measure Data

    Analysis Population Description
    The study terminated in 2009 due to poor enrollment. The principal investigator (PI) and study team are no longer at the institution and the PI has confirmed that the data no longer exists. There are no data to report.
    Arm/Group Title Simvastatin
    Arm/Group Description Escalating dose of simvastatin Simvastatin: All patients will start at 10mg of simvastatin, and then, based on results of interim evaluation escalated to 20mg and then 40. Patients will stay on maximally tolerated dose of drug until the end of the study at 26 weeks.
    Measure Participants 0

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Simvastatin
    Arm/Group Description Escalating dose of simvastatin Simvastatin: All patients will start at 10mg of simvastatin, and then, based on results of interim evaluation escalated to 20mg and then 40. Patients will stay on maximally tolerated dose of drug until the end of the study at 26 weeks.
    All Cause Mortality
    Simvastatin
    Affected / at Risk (%) # Events
    Total / (NaN)
    Serious Adverse Events
    Simvastatin
    Affected / at Risk (%) # Events
    Total 0/3 (0%)
    Other (Not Including Serious) Adverse Events
    Simvastatin
    Affected / at Risk (%) # Events
    Total 2/3 (66.7%)
    Musculoskeletal and connective tissue disorders
    Creatine Kinase 1/3 (33.3%) 1
    Skin and subcutaneous tissue disorders
    Rash 1/3 (33.3%) 1

    Limitations/Caveats

    Early termination due to poor accrual

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Jennifer Levine, MD
    Organization Weill Cornell Medicine
    Phone 212-305-9770
    Email jel9022@med.cornell.edu
    Responsible Party:
    Columbia University
    ClinicalTrials.gov Identifier:
    NCT00746603
    Other Study ID Numbers:
    • AAAB4447
    First Posted:
    Sep 4, 2008
    Last Update Posted:
    Mar 2, 2021
    Last Verified:
    Feb 1, 2021