ClinicalTrials.gg
RecruitingNCT01790152Updated May 18, 2026

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

An observational study in Hodgkin Lymphoma in Remission, Leukemia in Remission and Lymphoblastic Lymphoma, sponsored by Children's Oncology Group. Recruiting at 79 sites in 4 countries. Per ClinicalTrials.gov, last updated 2026-05-18.

Sponsored by Children's Oncology Group · Observational

From the registry’s dates

  • Started Mar 2014; still recruiting 12 years 8 months later.
Study type
Observational
Model
Case-only
Time perspective
Prospective
Enrollment
420
Sex
All
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Study 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.

Read the detailed description

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.

02

Conditions studied

  • Hodgkin Lymphoma in Remission
  • Leukemia in Remission
  • Lymphoblastic Lymphoma
  • Osteosarcoma
  • Recurrent Leukemia
  • Recurrent Lymphoma
  • Recurrent Malignant Neoplasm
03

In context

Precursor Cell Lymphoblastic Leukemia-Lymphoma

2,584 studies on the registry are indexed under Precursor Cell Lymphoblastic Leukemia-Lymphoma; 473 are open to participants now.

This study's planned enrollment of 420 is above the median of 108 across 400 observational studies indexed under Precursor Cell Lymphoblastic Leukemia-Lymphoma.

Browse Precursor Cell Lymphoblastic Leukemia-Lymphoma studies →

Lead sponsor

Children's Oncology Group is the lead sponsor of 448 studies on the registry; 36 are open to participants now.

Of its 12 completed or terminated interventional studies of FDA-regulated products, 11 (92%) have results posted.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
No
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

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 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
  • 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 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 -proven moderate or high grade osteosarcoma without ; 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 >= 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
Terms in these criteria, in plain language(6)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Relapsed and refractory

Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.

Biopsy and archival tissue

A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.

Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

LVEF (left ventricular ejection fraction)

The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.

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Study design

Observational model
Case-only
Time perspective
Prospective
Enrollment
420 participants (estimated)
Biospecimen retention
Samples with dna

Groups and cohorts

  • 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

  • OtherAssessment of Therapy Complications

    Ancillary studies

  • OtherLaboratory Biomarker Analysis

    Correlative studies

  • OtherQuality-of-Life Assessment

    Ancillary studies

    Also known as: Quality of Life Assessment

  • OtherQuestionnaire Administration

    Ancillary studies

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Baseline

  2. 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.

    Time frame: Baseline

Secondary outcomes

  1. Quality of life based on self-report instruments

    An analytic Markov model will be created and used. Estimates and their 95% confidence will be included to explore the sensitivity of any quality-adjusted life years estimates.

    Time frame: Baseline

  2. Primary disease relapse

    An analytic Markov model will be created and used.

    Time frame: Baseline

  3. Second cancer rates

    An analytic Markov model will be created and used.

    Time frame: Baseline

  4. Longitudinal trajectory of 2-dimensional echocardiographic parameters

    Will utilize generalized linear model-general estimation equation to model the trajectories of echocardiographic biomarker estimates (continuous outcomes) across time. Relevant model shapes will be evaluated, beginning with linear models, but also testing more flexible shapes (e.g., quadratic, cubic, or cubic spline functions with varying numbers of knots) to determine whether non-linear components are needed for fit. Will also examine interactions of dexrazoxane (DRZ) status with the selected functions of time to evaluate for differences in trajectories over time by DRZ status.

    Time frame: From time of cancer treatment to subsequent follow-up

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Study locations

62 of 79 sites recruiting
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References and documents

Publications

  • 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. PubMed 36669148 ↗
  • 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. PubMed 34810210 ↗
  • 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. PubMed 34644414 ↗
  • 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. PubMed 26014292 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 18, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT01790152
Responsible party
Sponsor
First posted
Feb 13, 2013
Start date
Mar 5, 2014
Primary completion
Dec 31, 2022
Completion
Dec 31, 2026 (estimated)
Last update
May 18, 2026

Study contacts

Eric J Chow
principal investigator · Children's Oncology Group

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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