Health Effects After Anthracycline and Radiation Therapy (HEART): Dexrazoxane and Prevention of Anthracycline-related Cardiomyopathy
N/A
N/A
Both
T-cell Acute Lymphoblastic Leukemia, Intermediate/Advanced Hodgkins, Early Hodgkins
Trial Information
Health Effects After Anthracycline and Radiation Therapy (HEART): Dexrazoxane and Prevention of Anthracycline-related Cardiomyopathy
Given the critical role anthracyclines have in many effective cancer treatments and the risk
for subsequent cardiotoxicity associated with this class of agents, development of an
effective cardioprotective strategy is of great importance. Although adult studies have
shown that dexrazoxane (DRZ) is effective in minimizing cardiomyopathy/heart failure (CHF)
after anthracycline therapy, short and long-term data in children are much more limited.
Furthermore, concerns regarding DRZ's interaction with cancer therapies and possible
association with an increased risk of second cancers have limited its use among children
despite possible protection against premature CHF. To address these gaps in knowledge, using
a cross-sectional study design, we propose to ascertain echocardiographic and serum
biomarkers of cardiac injury in a cohort 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 that featured upfront DRZ randomization and a range
of anthracycline exposures commonly used in contemporary therapy (100-360 mg/m2
doxorubicin). Our primary aim will be to determine whether patients randomized to the
experimental DRZ arms have decreased markers of myocardial injury compared with patients
treated without DRZ. Specifically, 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 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). In secondary analysis, we will also update the overall-
and event-free survival rates between patients on the DRZ and non-DRZ arms. Finally, we will
determine whether projected quality-adjusted life years differed by randomization status,
accounting for premature cardiac disease, primary disease relapse, and second cancers.
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:
-
Type of Study:
Observational
Study Design:
Observational Model: Case Control, Time Perspective: Prospective
Outcome Measure:
Left ventricular (LV) thickness-to-dimension ratio
Outcome Description:
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.
Outcome Time Frame:
2 years
Safety Issue:
No
Principal Investigator
Eric J Chow, MD, MPH
Investigator Role:
Study Chair
Investigator Affiliation:
Fred Hutchinson Cancer Research Center
Authority:
United States: Federal Government
Study ID:
ALTE11C2
NCT ID:
NCT01790152
Start Date:
March 2013
Completion Date:
Related Keywords:
- T-cell Acute Lymphoblastic Leukemia
- Intermediate/Advanced Hodgkins
- Early Hodgkins
- T-Cell Acute Lympoblastic Leukemia
- Hodkins
- Leukemia
- Leukemia, Lymphoid
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Cardiomyopathies
- Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Name | Location |
|---|---|
| Children's Oncology Group | Arcadia, California 91006-3776 |
