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Effects of Dexrazoxane Hydrochloride on Biomarkers Associated With Cardiomyopathy and Heart Failure After Cancer Treatment (HEART)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Children's Oncology Group
Sponsor:
Collaborators:
The Leukemia and Lymphoma Society
St. Baldrick's Foundation
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT01790152
First received: February 11, 2013
Last updated: August 6, 2014
Last verified: August 2014

February 11, 2013
August 6, 2014
August 2013
January 2019   (final data collection date for primary outcome measure)
Left ventricular (LV) thickness-to-dimension ratio [ Time Frame: 2 years ] [ Designated as safety issue: No ]
A decrease in echocardiographically derived measure of pathologic left ventricle (LV) remodeling which has been shown to be an important earlier surrogate measure of subsequent heart failure in both anthracycline-exposed pediatric cancer survivors5 and in the general pediatric and adult cardiomyopathy/heart failure population. This ratio can be derived from standard measurements.
Same as current
Complete list of historical versions of study NCT01790152 on ClinicalTrials.gov Archive Site
  • Differences in serum biomarkers [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Particularly cardiac troponins and natriuretic peptides associated with acute changes following anthracycline exposure will be examined. Analyses involving markers of inflammation (hs-CRP, TNF, IL6) and more novel markers associated with heart failure in the general population (galectin-3, ST2, growth differentiation factor-15) are exploratory.
  • Quality of life [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Based on self-report instruments will be factored into QALY estimates to answer the secondary aims.
  • Primary disease relapse [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    An analytic Markov model will be created and used.
  • Update primary disease relapse and second cancer rates [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Given additional elapsed time since last follow-up used in the prior published analyses,11-13 primary disease relapse and second cancer rates will be updated.
  • Differences in serum biomarkers [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Particularly cardiac troponins and natriuretic peptides associated with acute changes following anthracycline exposure will be examined. Analyses involving markers of inflammation (hs-CRP, TNF, IL6) and more novel markers associated with heart failure in the general population (galectin-3, ST2, growth differentiation factor-15) are exploratory.
  • Quality of Life [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Based on self-report instruments will be factored into QALY estimates to answer the secondary aims.
  • Update primary disease relapse and second cancer rates [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Given additional elapsed time since last follow-up used in the prior published analyses,11-13 primary disease relapse and second cancer rates will be updated.
Not Provided
Not Provided
 
Effects of Dexrazoxane Hydrochloride on Biomarkers Associated With Cardiomyopathy and Heart Failure After Cancer Treatment
Health Effects After Anthracycline and Radiation Therapy (HEART): Dexrazoxane and Prevention of Anthracycline-Related Cardiomyopathy

We will determine echocardiographic and serum biomarkers of cardiac injury in a study of long-term pediatric T-cell leukemia and Hodgkin lymphoma survivors enrolled on 3 front-line Children's Oncology Group (COG) clinical trials (POG 9404, 9425, 9426) between 1996-2001 with certain features. Our primary aim will be to determine whether patients randomized to the experimental dexrazoxane (DRZ) arms have decreased markers of myocardial injury compared with patients treated without dexrazoxane (DRZ). This will include a one-time measurement of an echocardiographic index of pathologic left ventricular (LV) remodeling (wall thickness-dimension ratio), complemented by serum biomarkers and a physical examination for signs and symptoms of cardiomyopathy/heart failure (CHF). We will also evaluate whether DRZ's cardioprotective effect is modified by anthracycline dose, chest radiation, and selected demographic factors (age at cancer diagnosis, current age, sex).

PRIMARY OBJECTIVES:

I. To determine whether patients randomized to the experimental dexrazoxane hydrochloride (DRZ) arms have decreased markers of cardiomyopathy/heart failure (CHF) compared with patients on the standard arm.

II. To evaluate whether the cardioprotective effect of DRZ is modified by anthracycline (anthracycline analogue GPX-150) dose, chest radiation, and demographic factors (age at cancer diagnosis, current age, sex).

SECONDARY OBJECTIVES:

I. To determine whether patients on the DRZ arms experienced differential rates of overall-survival and event-free survival compared with the standard therapy arms.

II. To determine whether projected quality-adjusted life years (QALY) differed by randomization status, accounting for premature cardiac disease, primary disease relapse, and second cancers.

OUTLINE:

Patients complete a diagnostic symptom checklist, undergo a physical exam, echocardiogram, collection of serum for biomarker testing, and a 6 minute walk test, and complete quality of life, family history, physical activity, and smoking questionnaires.

Observational
Observational Model: Case Control
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

serum

Probability Sample

Long-term pediatric T-cell leukemia and Hodgkin lymphoma survivors enrolled on 3 front-line Children's Oncology Group (COG) clinical trials (POG 9404, 9425, 9426) between 1996-2001 that featured upfront DRZ randomization and a range of anthracycline exposures commonly used in contemporary therapy (100-360 mg/m2 doxorubicin).

  • Recurrent Adult Hodgkin Lymphoma
  • Recurrent Adult T-cell Leukemia/Lymphoma
  • Recurrent/Refractory Childhood Hodgkin Lymphoma
  • Stage I Adult Hodgkin Lymphoma
  • Stage I Adult T-cell Leukemia/Lymphoma
  • Stage I Childhood Hodgkin Lymphoma
  • Stage II Adult Hodgkin Lymphoma
  • Stage II Adult T-cell Leukemia/Lymphoma
  • Stage II Childhood Hodgkin Lymphoma
  • Stage III Adult Hodgkin Lymphoma
  • Stage III Adult T-cell Leukemia/Lymphoma
  • Stage III Childhood Hodgkin Lymphoma
  • Stage IV Adult Hodgkin Lymphoma
  • Stage IV Adult T-cell Leukemia/Lymphoma
  • Stage IV Childhood Hodgkin Lymphoma
  • Other: Anthropometry

    Easily determined in-office physical exam parameters requested include:

    • Height
    • Weight
    • Waist circumference
    • Blood pressure (BP)
    • Heart rate
  • Other: Serum Biomarkers

    All participants will have the following analytes collected under standardized conditions and processed centrally.

    • Cardiac troponins have been associated with acute anthracycline-related cardiotoxicity, and newer high-sensitivity cTnT and cTnI assays may be predictive of late-occurring LV dysfunction. Natriuretic peptides (BNP, NT-ProBNP) are produced in response to myocardial wall stress and are used to monitor CHF progression. Levels, if persistently elevated, correlate well with echocardiographic indices of myocardial dysfunction. In exploratory analyses, we will also examine the effects of selected inflammatory biomarkers.
    • Fasting lipid profile (total cholesterol, HDL, LDL, triglyceride), glucose, insulin, and hemoglobin AIC)
    • Provide optional consent to have DNA banked for future research related to analysis of possible genetic polymorphisms associated with differential risk of cardiomyopathy.
  • Other: Diagnostic/symptom checklist
    The local PI or their designee (e.g. clinician, research nurse, or clinical research associate) will be asked to complete a diagnostic and symptom checklist (see Forms Packet on COG website) related to study outcomes. A copy of the participant's most recent clinic note and current medication list also are requested.
  • Procedure: Echocardiogram
    Study participants will undergo a one-time standard 2D, M-mode, and Doppler echocardiogram per AHA/ACC task force practice guidelines at participating institutions (or their adult affiliates depending on patient age and institutional practice).
  • Other: 6 minute walk test (6MWT)

    Ambulatory participants will be asked to undergo this simple test of functional exercise capacity.

    Contraindications include: 1.) history of angina or myocardial infarction within the past month, 2.) resting heart rate >120 bpm, 3.) systolic blood pressure >180 mmHg or diastolic blood pressure >100 mmHg. Any other reason for patient inability to perform this test should be documented in the respective Report Form.

  • Behavioral: Participant Questionnaires (ages >14 years only)

    The time to complete questionnaires is estimated less than 45 minutes. General health status and quality of life will be assessed using the Short-Form-36.

    Participants also will be administered the Minnesota Living with Heart Failure questionnaire.

    Questionnaires will ascertain family history of cardiovascular and related diseases (e.g. diabetes). Physical activity will be assessed using questions from the Centers for Disease Control & Prevention's (CDC) Behavioral Risk Factor Surveillance System exercise & physical activity modules. Smoking history (current & lifetime) will be assessed using questions from Health and Nutritional Examination surveys.

  • Ancillary-Correlative-Stratum 1 with diagnostic interventions

    Required observations are designed to be collected at one visit:

    Diagnostic/symptom checklist Anthropometry Echocardiogram Serum biomarkers Troponins (cTnT, cTnI) Natriuretic peptides (BNP, NT-ProBNP) Inflammation (hs-CRP, IL-6, TNF, Galectin-3, ST2, GDF15) Fasting glucose, lipid profile, insulin, hemoglobin AIC DNA 6 minute walk test Participant Questionnaires: Quality of life, family history, physical activity, and smoking Fasting for at least 10 hours prior to the study blood draw.

    Interventions:
    • Other: Anthropometry
    • Other: Serum Biomarkers
    • Other: Diagnostic/symptom checklist
    • Procedure: Echocardiogram
    • Other: 6 minute walk test (6MWT)
    • Behavioral: Participant Questionnaires (ages >14 years only)
  • Stratum 2 Relapse and subsequent malignancy status
    Patients not eligible for Stratum 1 may still contribute data to the Secondary Aims: Relapse and subsequent malignancy status
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
420
Not Provided
January 2019   (final data collection date for primary outcome measure)

Long-term pediatric T-cell leukemia and Hodgkin lymphoma survivors enrolled on 3 front-line Children's Oncology Group (COG) clinical trials (POG 9404, 9425, 9426) between 1996-2001 that featured upfront DRZ randomization and a range of anthracycline exposures commonly used in contemporary therapy (100-360 mg/m2 doxorubicin).

Sampling Method: Non-Probability Sample Genders Eligible for Study: Both

Inclusion Criteria:

  • Previously enrolled and randomized on POG 9404, 9425, or 9426
  • Alive and in continuous first complete remission from their original cancer (T-cell leukemia/lymphoma [POG 9404] or Hodgkin lymphoma [POG 9425/9426])
  • Not have been diagnosed with any subsequent malignancy, with the exception of non-melanomatous skin cancer(s). Patients with history of only subsequent non-melanomatous skin cancers remain eligible.
  • All patients and/or their parents or legal guardians must sign a written informed consent (see Stratum 1 sample consent).
  • Among patients who have relapsed or have experienced a subsequent malignancy other than non-melanomatous skin cancer since their original diagnosis, the study committee will review the available data (both from COG's Statistics and Data Center (SDC) and the participating institution) to determine if individual patients are to be selected for secondary aim arm only. The study will petition the IRB specifically for a waiver of consent to include any relapse and subsequent cancer data obtained from existing records for analysis of the secondary aims. Patients selected for Stratum 2 will be those for whom late relapse or subsequent cancer is reported but who lack clear confirmation in existing records (either at SDC or at the local institution).

Exclusion Criteria:

-

Both
Not Provided
No
United States,   Canada
 
NCT01790152
ALTE11C2, NCI-2012-03196, S0004187, ALTE11C2, COG-ALTE11C2, ALTE11C2, U10CA095861
No
Children's Oncology Group
Children's Oncology Group
  • The Leukemia and Lymphoma Society
  • St. Baldrick's Foundation
  • National Cancer Institute (NCI)
Principal Investigator: Eric Chow, MD, MPH Children's Oncology Group
Children's Oncology Group
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP