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
  Purpose

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).


Condition Intervention
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
Other: Serum Biomarkers
Other: Diagnostic/symptom checklist
Procedure: Echocardiogram
Other: 6 minute walk test (6MWT)
Behavioral: Participant Questionnaires (ages >14 years only)

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Health Effects After Anthracycline and Radiation Therapy (HEART): Dexrazoxane and Prevention of Anthracycline-Related Cardiomyopathy

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Biospecimen Retention:   Samples With DNA

serum


Estimated Enrollment: 420
Study Start Date: August 2013
Estimated Primary Completion Date: January 2019 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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.

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.

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

Detailed Description:

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

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).

Criteria

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:

-

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01790152

  Show 33 Study Locations
Sponsors and Collaborators
Children's Oncology Group
The Leukemia and Lymphoma Society
St. Baldrick's Foundation
Investigators
Principal Investigator: Eric Chow, MD, MPH Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT01790152     History of Changes
Other Study ID Numbers: ALTE11C2, NCI-2012-03196, S0004187, ALTE11C2, COG-ALTE11C2, ALTE11C2, U10CA095861
Study First Received: February 11, 2013
Last Updated: August 6, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Heart Diseases
Hodgkin Disease
Cardiomyopathies
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cardiovascular Diseases
Leukemia, Lymphoid
Dexrazoxane
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Cardiotonic Agents
Cardiovascular Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 19, 2014