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

NCT01790152 | Recruiting

• 6 other identifiers: ALTE11C2S0004187COG-ALTE11C2R01CA211996U10CA095861UG1CA189955
• Study Type: observational
• Target: 420
• Locations: 4 countries
• Sites: 79

Brief Summary

This clinical trial studies the effects of dexrazoxane hydrochloride on biomarkers associated with cardiomyopathy and heart failure after cancer treatment. Studying samples of blood in the laboratory from patients receiving dexrazoxane hydrochloride may help doctors learn more about the effects of dexrazoxane hydrochloride on cells. It may also help doctors understand how well patients respond to treatment.

Conditions

Hodgkin Lymphoma in Remission; Leukemia in Remission; Lymphoblastic Lymphoma; Osteosarcoma; Recurrent Leukemia; Recurrent Lymphoma; Recurrent Malignant Neoplasm

Outcome Measures

Primary Outcomes (2)

• Left ventricular function and measures of pathologic remodeling (i.e., thickness-to-dimension ratio) assessed using standard 2-dimensional, M-mode, and Doppler echocardiogram

  Univariate tests will be used as well as examination of the entire cohort via multivariable regression adjusting for all a priori covariates of interest.

  Baseline

• Differences in serum biomarkers (particularly cardiac troponins and natriuretic peptides)

  Univariate tests will be used as well as examination of the entire cohort via multivariable regression adjusting for all a priori covariates of interest.

  Baseline

Secondary Outcomes (4)

• Quality of life based on self-report instruments

  Baseline

• Primary disease relapse

  Baseline

• Second cancer rates

  Baseline

• Longitudinal trajectory of 2-dimensional echocardiographic parameters

  From time of cancer treatment to subsequent follow-up

Study Arms (1)

Ancillary-Correlative (laboratory biomarker analysis)

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.

Other: Assessment of Therapy Complications; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Assessment of Therapy Complications OTHER

Ancillary studies

Ancillary-Correlative (laboratory biomarker analysis)

Laboratory Biomarker Analysis OTHER

Correlative studies

Ancillary-Correlative (laboratory biomarker analysis)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Ancillary-Correlative (laboratory biomarker analysis)

Questionnaire Administration OTHER

Ancillary studies

Ancillary-Correlative (laboratory biomarker analysis)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with leukemia or lymphoma enrolled on Pediatric Oncology Group (POG) P9404, P9425, P9426, and DFCI 95-01 or osteosarcoma enrolled on P9754

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (79)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

RECRUITING

Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States

RECRUITING

Banner University Medical Center - Tucson

Tucson, Arizona, 85719, United States

RECRUITING

Arkansas Children's Hospital

Little Rock, Arkansas, 72202-3591, United States

RECRUITING

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

RECRUITING

Valley Children's Hospital

Madera, California, 93636, United States

ACTIVE NOT RECRUITING

Kaiser Permanente-Oakland

Oakland, California, 94611, United States

RECRUITING

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, 94304, United States

RECRUITING

Rady Children's Hospital - San Diego

San Diego, California, 92123, United States

RECRUITING

Yale University

New Haven, Connecticut, 06520, United States

RECRUITING

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, 33908, United States

RECRUITING

University of Florida Health Science Center - Gainesville

Gainesville, Florida, 32610, United States

SUSPENDED

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida, 33021, United States

ACTIVE NOT RECRUITING

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, 32207, United States

RECRUITING

Nemours Children's Hospital

Orlando, Florida, 32827, United States

RECRUITING

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

ACTIVE NOT RECRUITING

Saint Joseph's Hospital/Children's Hospital-Tampa

Tampa, Florida, 33607, United States

RECRUITING

Saint Mary's Hospital

West Palm Beach, Florida, 33407, United States

RECRUITING

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, 30322, United States

RECRUITING

University of Hawaii Cancer Center

Honolulu, Hawaii, 96813, United States

ACTIVE NOT RECRUITING

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, 96826, United States

RECRUITING

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

RECRUITING

University of Illinois

Chicago, Illinois, 60612, United States

ACTIVE NOT RECRUITING

Advocate Children's Hospital-Oak Lawn

Oak Lawn, Illinois, 60453, United States

RECRUITING

Saint Jude Midwest Affiliate

Peoria, Illinois, 61637, United States

RECRUITING

Ochsner Medical Center Jefferson

New Orleans, Louisiana, 70121, United States

RECRUITING

Maine Children's Cancer Program

Scarborough, Maine, 04074, United States

RECRUITING

Sinai Hospital of Baltimore

Baltimore, Maryland, 21215, United States

RECRUITING

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

ACTIVE NOT RECRUITING

Ascension Saint John Hospital

Detroit, Michigan, 48236, United States

RECRUITING

Hurley Medical Center

Flint, Michigan, 48503, United States

ACTIVE NOT RECRUITING

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

RECRUITING

Columbia Regional

Columbia, Missouri, 65201, United States

ACTIVE NOT RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

University Medical Center of Southern Nevada

Las Vegas, Nevada, 89102, United States

RECRUITING

Sunrise Hospital and Medical Center

Las Vegas, Nevada, 89109, United States

RECRUITING

Alliance for Childhood Diseases/Cure 4 the Kids Foundation

Las Vegas, Nevada, 89135, United States

RECRUITING

Summerlin Hospital Medical Center

Las Vegas, Nevada, 89144, United States

RECRUITING

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

ACTIVE NOT RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87102, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

SUSPENDED

The Steven and Alexandra Cohen Children's Medical Center of New York

New Hyde Park, New York, 11040, United States

RECRUITING

University of Rochester

Rochester, New York, 14642, United States

RECRUITING

Stony Brook University Medical Center

Stony Brook, New York, 11794, United States

RECRUITING

State University of New York Upstate Medical University

Syracuse, New York, 13210, United States

RECRUITING

Mission Hospital

Asheville, North Carolina, 28801, United States

RECRUITING

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

RECRUITING

Children's Hospital Medical Center of Akron

Akron, Ohio, 44308, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Legacy Emanuel Children's Hospital

Portland, Oregon, 97227, United States

RECRUITING

Oregon Health and Science University

Portland, Oregon, 97239, United States

RECRUITING

Saint Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134, United States

RECRUITING

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

RECRUITING

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

BI-LO Charities Children's Cancer Center

Greenville, South Carolina, 29605, United States

RECRUITING

Medical City Dallas Hospital

Dallas, Texas, 75230, United States

ACTIVE NOT RECRUITING

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

RECRUITING

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

SUSPENDED

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

RECRUITING

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

University of Vermont and State Agricultural College

Burlington, Vermont, 05405, United States

RECRUITING

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

RECRUITING

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, 99204, United States

RECRUITING

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Princess Margaret Hospital for Children

Perth, Western Australia, 6008, Australia

ACTIVE NOT RECRUITING

Perth Children's Hospital

Perth, Western Australia, 6009, Australia

RECRUITING

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

RECRUITING

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, L8N 3Z5, Canada

SUSPENDED

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

ACTIVE NOT RECRUITING

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

SUSPENDED

The Montreal Children's Hospital of the MUHC

Montreal, Quebec, H3H 1P3, Canada

RECRUITING

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

RECRUITING

Centre Hospitalier Universitaire de Quebec

Québec, G1V 4G2, Canada

RECRUITING

San Jorge Children's Hospital

San Juan, 00912, Puerto Rico

RECRUITING

Related Publications (4)

• Chow EJ, Aggarwal S, Doody DR, Aplenc R, Armenian SH, Baker KS, Bhatia S, Blythe N, Colan SD, Constine LS, Freyer DR, Kopp LM, Laverdiere C, Leisenring WM, Sasaki N, Vrooman LM, Asselin BL, Schwartz CL, Lipshultz SE. Dexrazoxane and Long-Term Heart Function in Survivors of Childhood Cancer. J Clin Oncol. 2023 Apr 20;41(12):2248-2257. doi: 10.1200/JCO.22.02423. Epub 2023 Jan 20.

  PMID: 36669148 RESULT

• Lipshultz ER, Chow EJ, Doody DR, Armenian SH, Asselin BL, Baker KS, Bhatia S, Constine LS, Freyer DR, Kopp LM, Schwartz CL, Lipshultz SE, Vrooman LM. Cardiometabolic Risk in Childhood Cancer Survivors: A Report from the Children's Oncology Group. Cancer Epidemiol Biomarkers Prev. 2022 Mar 1;31(3):536-542. doi: 10.1158/1055-9965.EPI-21-0360.

  PMID: 34810210 RESULT

• Chow EJ, Aplenc R, Vrooman LM, Doody DR, Huang YV, Aggarwal S, Armenian SH, Baker KS, Bhatia S, Constine LS, Freyer DR, Kopp LM, Leisenring WM, Asselin BL, Schwartz CL, Lipshultz SE. Late health outcomes after dexrazoxane treatment: A report from the Children's Oncology Group. Cancer. 2022 Feb 15;128(4):788-796. doi: 10.1002/cncr.33974. Epub 2021 Oct 13.

  PMID: 34644414 RESULT

• Chow EJ, Asselin BL, Schwartz CL, Doody DR, Leisenring WM, Aggarwal S, Baker KS, Bhatia S, Constine LS, Freyer DR, Lipshultz SE, Armenian SH. Late Mortality After Dexrazoxane Treatment: A Report From the Children's Oncology Group. J Clin Oncol. 2015 Aug 20;33(24):2639-45. doi: 10.1200/JCO.2014.59.4473. Epub 2015 May 26.

  PMID: 26014292 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Serum

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Osteosarcoma; Leukemia; Lymphoma; Recurrence

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Eric J Chow

  Children's Oncology Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2013
• First Posted: February 13, 2013
• Study Start: March 5, 2014
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2025
• Last Updated: May 23, 2025

Record last verified: 2025-05

Locations

CA (7); AU (2); PR (1); US (69)