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Effects of Dexrazoxane Hydrochloride on Biomarkers Associated With Cardiomyopathy and Heart Failure After Cancer Treatment
NCT01790152 · Children's Oncology Group
In plain English
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Official title
Health Effects After Anthracycline and Radiation Therapy (HEART): Dexrazoxane and Prevention of Anthracycline-Related Cardiomyopathy
About this study
PRIMARY OBJECTIVES:
I. To determine whether leukemia and lymphoma patients from P9404, P9425, P9426, and Dana Farber Cancer Institute (DFCI) 95-01 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 determine whether osteosarcoma patients from P9754 (all received DRZ) have decreased markers of cardiomyopathy/heart failure (CHF) compared with similarly treated osteosarcoma patients diagnosed during the same time period, but who did not receive DRZ.
III. 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 leukemia and lymphoma patients from P9404, P9425, P9426, and DFCI 95-01 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 DRZ status, accounting for premature cardiac disease, primary disease relapse, and second cancers.
III. Determine the longitudinal trajectory of 2-dimensional echocardiographic parameters (focusing on left ventricular \[LV\] function and remodeling/geometric changes that can be reliably re-measured) among patients from time of cancer treatment through subsequent follow-up.
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 criteria
Inclusion Criteria:
Study Strata I, II, and III are closed for further patient entry as of March 31, 2021. The study remains open for existing medical record submission of Stratum IV
* STRATUM I AND STRATUM II: LEUKEMIA AND LYMPHOMA SURVIVORS
* Previously enrolled leukemia and lymphoma survivors, randomized to + or - DRZ on P9404, P9425, P9426, or DFCI 95-01 (high-risk patients only)
* STRATUM I: Alive and in continuous first complete remission from their original cancer (leukemia/lymphoblastic lymphoma \[P9404, high-risk DFCI 95-01\] or Hodgkin lymphoma \[P9425/P9426\])
* STRATUM I: Did not have progressive disease or induction failure requiring off-protocol therapy including hematopoietic cell transplantation
* STRATUM I: Must not have been diagnosed with any subsequent malignancy that required additional cardiotoxic therapies (i.e., radiotherapy to the chest \[also includes fields directed towards the neck, upper abdomen, or spine\], or additional anthracyclines or anthraquinones); patients with history of subsequent malignancy that did not require such therapies remain eligible
* STRATUM I: All patients and/or their parents or legal guardians must sign a written informed consent
* STRATUM II: Among leukemia and lymphoma patients randomized to + or - DRZ on P9404, P9425, P9426, and DFCI 95-01 (high risk patients only) who have relapsed or have experienced a subsequent malignancy that precludes eligibility since their original diagnosis, the study committee will review the available data (both from Children's Oncology Group's \[COG?s\] Statistics and Data Center \[SDC\] and the participating institution) to determine if individual patients are to be selected for Stratum 2; in recognition that local institutions sometimes have more updated relapse/subsequent cancer data than SDC, in cases where local data is more updated, local data will be used preferentially; the study will petition the Institutional Review Board (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)
* STRATUM II: Alive, but have experienced relapse of their original cancer and/or have developed a subsequent cancer (other than non-melanomatous skin cancer) since their original diagnosis
* STRATUM II: All patients and/or their parents or legal guardians must sign a written informed consent
* STRATUM III: OSTEOSARCOMA SURVIVORS
* Previously enrolled osteosarcoma survivors treated on P9754 who are alive and able (themselves and/or parents/legal guardian) to provide written informed consent; note that relapse and subsequent malignancy are not exclusion criteria for P9754 survivors
* Comparison subjects for P9754 survivors will be eligible to be enrolled from any ALTE11C2 participating COG site (even if that institution did not participate on P9754), according to the following criteria:
* Newly diagnosed, previously untreated biopsy-proven moderate or high grade osteosarcoma without metastasis; patients with low grade osteosarcoma, parosteal or periosteal sarcoma are ineligible
* \< 31 years of age at time of initial osteosarcoma diagnosis
* Diagnosis occurred between January 1, 1999 through December 31, 2002; duration of therapy can extend beyond 2002
* No evidence of poor or low cardiac function at time of initial osteosarcoma diagnosis; if reports from the time are available: shortening fraction \>= 28% by echocardiogram and within the institutional normative range for age, or radionuclide angiogram ejection fraction \>= 50%; if imaging reports from the time are no longer available, there must be no documentation within available medical records that suggest poor or low cardiac function at time of diagnosis
* Comparison subject must have institutional records (e.g., clinic note, treatment summary, chemotherapy roadmap) documenting lifetime receipt of 450 to 600 mg/m\^2 of doxorubicin (doses within 10% are acceptable); this includes initial therapy as well as any subsequent therapy for relapse or second cancer, if relevant; as such, comparison subjects who have had osteosarcoma relapse or subsequent malignancies remain eligible so long as they meet all other eligibility criteria
* No anthracycline or anthraquinone aside from doxorubicin was ever given as part of initial or subsequent therapies
* No exposure to DRZ at any point in time
* All patients and/or their parents or legal guardians must sign a written informed consent
* STRATUM IV: CARDIOMYOPATHY CASES, NOT OTHERWISE ELIGIBLE FOR STRATUMS 1, 2, AND 3
* Individuals diagnosed with cancer prior to age 21 years, who required treatment with chemotherapy and/or radiotherapy, achieved initial remission, and remained alive after completing anti-cancer-therapy for at least 1 year
* Must have screening echocardiograms for heart function as part of cancer therapy and off-therapy evaluations available (Digital Imaging and Communications in Medicine \[DICOM\] format). Images from Video Home System (VHS) tapes and reports only (without images) are not suitable
* Cannot have a known history of congenital heart disease (patent foramen ovale remain eligible) or underlying genetic syndrome associated with abnormal cardiovascular development or health (e.g., down syndrome)
* Based on echocardiography, must have either left ventricular fractional shortening =\< 28.0% or ejection fraction =\< 50.0% on at least two occasions, with at least one of these measurements occurring after cancer therapy completion and be in the absence of sepsis or any uncontrolled infection
* If the fractional shortening or ejection fraction criteria is only met on one occasion, this must be after cancer therapy completion, be in the absence of sepsis or any uncontrolled infection, and the patient must have subsequently started on chronic medical therapy for cardiomyopathy (e.g., beta-blocker, angiotensin-converting enzyme \[ACE\]-inhibitor, angiotensin receptor blocker) lasting at least 6 months
* For all participants (stratums 1, 2, 3, and 4), all institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Study design
Enrollment target: 420 participants
Age groups: child, adult, older_adult
Timeline
Starts: 2014-03-05
Estimated completion: 2025-12-31
Last updated: 2025-05-23
Interventions
Other: Assessment of Therapy ComplicationsOther: Laboratory Biomarker AnalysisOther: Quality-of-Life AssessmentOther: Questionnaire Administration
Primary outcomes
- • Left ventricular function and measures of pathologic remodeling (i.e., thickness-to-dimension ratio) assessed using standard 2-dimensional, M-mode, and Doppler echocardiogram (Baseline)
- • Differences in serum biomarkers (particularly cardiac troponins and natriuretic peptides) (Baseline)
Sponsor
Children's Oncology Group · network
With: National Cancer Institute (NCI)
Contacts & investigators
InvestigatorEric J Chow · principal_investigator, Children's Oncology Group
All locations (79)
Children's Hospital of AlabamaRecruiting
Birmingham, Alabama, United States
Phoenix Childrens HospitalRecruiting
Phoenix, Arizona, United States
Banner University Medical Center - TucsonRecruiting
Tucson, Arizona, United States
Arkansas Children's HospitalRecruiting
Little Rock, Arkansas, United States
City of Hope Comprehensive Cancer CenterRecruiting
Duarte, California, United States
Valley Children's HospitalActive Not Recruiting
Madera, California, United States
Kaiser Permanente-OaklandRecruiting
Oakland, California, United States
Lucile Packard Children's Hospital Stanford UniversityRecruiting
Palo Alto, California, United States
Rady Children's Hospital - San DiegoRecruiting
San Diego, California, United States
Yale UniversityRecruiting
New Haven, Connecticut, United States
Golisano Children's Hospital of Southwest FloridaRecruiting
Fort Myers, Florida, United States
University of Florida Health Science Center - GainesvilleSuspended
Gainesville, Florida, United States
Memorial Regional Hospital/Joe DiMaggio Children's HospitalActive Not Recruiting
Hollywood, Florida, United States
Nemours Children's Clinic-JacksonvilleRecruiting
Jacksonville, Florida, United States
Nemours Children's HospitalRecruiting
Orlando, Florida, United States
Johns Hopkins All Children's HospitalActive Not Recruiting
St. Petersburg, Florida, United States
Saint Joseph's Hospital/Children's Hospital-TampaRecruiting
Tampa, Florida, United States
Saint Mary's HospitalRecruiting
West Palm Beach, Florida, United States
Children's Healthcare of Atlanta - EglestonRecruiting
Atlanta, Georgia, United States
University of Hawaii Cancer CenterActive Not Recruiting
Honolulu, Hawaii, United States
Kapiolani Medical Center for Women and ChildrenRecruiting
Honolulu, Hawaii, United States
Lurie Children's Hospital-ChicagoRecruiting
Chicago, Illinois, United States
University of IllinoisActive Not Recruiting
Chicago, Illinois, United States
Advocate Children's Hospital-Oak LawnRecruiting
Oak Lawn, Illinois, United States
Saint Jude Midwest AffiliateRecruiting
Peoria, Illinois, United States
Ochsner Medical Center JeffersonRecruiting
New Orleans, Louisiana, United States
Maine Children's Cancer ProgramRecruiting
Scarborough, Maine, United States
Sinai Hospital of BaltimoreRecruiting
Baltimore, Maryland, United States
Johns Hopkins University/Sidney Kimmel Cancer CenterRecruiting
Baltimore, Maryland, United States
Dana-Farber Cancer InstituteRecruiting
Boston, Massachusetts, United States
Wayne State University/Karmanos Cancer InstituteActive Not Recruiting
Detroit, Michigan, United States
Ascension Saint John HospitalRecruiting
Detroit, Michigan, United States
Hurley Medical CenterActive Not Recruiting
Flint, Michigan, United States
University of Mississippi Medical CenterRecruiting
Jackson, Mississippi, United States
Columbia RegionalActive Not Recruiting
Columbia, Missouri, United States
Washington University School of MedicineRecruiting
St Louis, Missouri, United States
University Medical Center of Southern NevadaRecruiting
Las Vegas, Nevada, United States
Sunrise Hospital and Medical CenterRecruiting
Las Vegas, Nevada, United States
Alliance for Childhood Diseases/Cure 4 the Kids FoundationRecruiting
Las Vegas, Nevada, United States
Summerlin Hospital Medical CenterRecruiting
Las Vegas, Nevada, United States
Dartmouth Hitchcock Medical CenterActive Not Recruiting
Lebanon, New Hampshire, United States
Hackensack University Medical CenterRecruiting
Hackensack, New Jersey, United States
University of New Mexico Cancer CenterRecruiting
Albuquerque, New Mexico, United States
Roswell Park Cancer InstituteSuspended
Buffalo, New York, United States
The Steven and Alexandra Cohen Children's Medical Center of New YorkRecruiting
New Hyde Park, New York, United States
University of RochesterRecruiting
Rochester, New York, United States
Stony Brook University Medical CenterRecruiting
Stony Brook, New York, United States
State University of New York Upstate Medical UniversityRecruiting
Syracuse, New York, United States
Mission HospitalRecruiting
Asheville, North Carolina, United States
Wake Forest University Health SciencesRecruiting
Winston-Salem, North Carolina, United States
Children's Hospital Medical Center of AkronRecruiting
Akron, Ohio, United States
Cincinnati Children's Hospital Medical CenterRecruiting
Cincinnati, Ohio, United States
University of Oklahoma Health Sciences CenterRecruiting
Oklahoma City, Oklahoma, United States
Legacy Emanuel Children's HospitalRecruiting
Portland, Oregon, United States
Oregon Health and Science UniversityRecruiting
Portland, Oregon, United States
Saint Christopher's Hospital for ChildrenRecruiting
Philadelphia, Pennsylvania, United States
Rhode Island HospitalRecruiting
Providence, Rhode Island, United States
Medical University of South CarolinaRecruiting
Charleston, South Carolina, United States
BI-LO Charities Children's Cancer CenterRecruiting
Greenville, South Carolina, United States
Medical City Dallas HospitalActive Not Recruiting
Dallas, Texas, United States
UT Southwestern/Simmons Cancer Center-DallasRecruiting
Dallas, Texas, United States
Cook Children's Medical CenterSuspended
Fort Worth, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer CenterRecruiting
Houston, Texas, United States
University of Texas Health Science Center at San AntonioRecruiting
San Antonio, Texas, United States
University of Vermont and State Agricultural CollegeRecruiting
Burlington, Vermont, United States
Virginia Commonwealth University/Massey Cancer CenterRecruiting
Richmond, Virginia, United States
Seattle Children's HospitalRecruiting
Seattle, Washington, United States
Providence Sacred Heart Medical Center and Children's HospitalRecruiting
Spokane, Washington, United States
Children's Hospital of WisconsinRecruiting
Milwaukee, Wisconsin, United States
Princess Margaret Hospital for ChildrenActive Not Recruiting
Perth, Western Australia, Australia
Perth Children's HospitalRecruiting
Perth, Western Australia, Australia
Alberta Children's HospitalRecruiting
Calgary, Alberta, Canada
McMaster Children's Hospital at Hamilton Health SciencesSuspended
Hamilton, Ontario, Canada
Children's Hospital of Eastern OntarioActive Not Recruiting
Ottawa, Ontario, Canada
Hospital for Sick ChildrenSuspended
Toronto, Ontario, Canada
The Montreal Children's Hospital of the MUHCRecruiting
Montreal, Quebec, Canada
Centre Hospitalier Universitaire Sainte-JustineRecruiting
Montreal, Quebec, Canada
Centre Hospitalier Universitaire de QuebecRecruiting
Québec, Canada
San Jorge Children's HospitalRecruiting
San Juan, Puerto Rico