The CARDIOPROTECT Trial
A Randomized Study of Dexrazoxane or Liposomal Doxorubicin in Newly Diagnosed Diffuse Large B-cell Lymphoma at High Risk for Heart Failure Events: the CARDIOPROTECT Trial
1 other identifier
interventional
60
1 country
1
Brief Summary
This trial is to evaluate if dexrazoxane is safer and more effective than liposomal doxorubicin in preventing heart failure events in participants with diffuse large B-cell lymphoma (DLBCL) undergoing either standard of care R-CHOP or pola-R-CHP treatment regiments. The names of the study drugs involved in this study are:
- Dexrazoxane (a type of Topoisomerase II Inhibitor)
- Liposomal Doxorubicin (a type of Topoisomerase II Inhibitor)
- Standard of care R-CHOP treatment regimen (Cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab)
- Standard of care pola-R-CHP treatment regimen: Cyclophosphamide, doxorubicin, polatuzumab vedotin-piiq, prednisone, rituximab
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Oct 2026
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 12, 2026
CompletedFirst Posted
Study publicly available on registry
June 17, 2026
CompletedStudy Start
First participant enrolled
October 2, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2030
Study Completion
Last participant's last visit for all outcomes
December 31, 2035
June 17, 2026
June 1, 2026
4.2 years
June 12, 2026
June 12, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Left Ventricular Ejection Fraction (LVEF)
LVEF represents the proportion of blood ejected from the left ventricle during each heartbeat and is calculated as LVEF=(ECV-ESV)/EDV, where EDV is the end-diastolic volume (the volume of blood in the ventricle at the end of filling) and ESV is the end-systolic volume (the volume of blood remaining in the ventricle after contraction).
LVEF will be assessed by echocardiography 3 months after completion of front-line chemotherapy, with chemotherapy administered for up to 18 weeks.
Secondary Outcomes (12)
Time to First Heart Failure (HF) Events
Up to 5 years
Time to Recurrent Heart Failure (HF) Events
Up to 5 years
Changes in 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12) Score from Baseline
Health status will be assessed at baseline, at cycle 3 of chemotherapy, at 3 and 12 months post-chemotherapy, and annually through 5 years, with chemotherapy administered for up to 18 weeks.
Changes in Patient-Reported Outcomes Measurement Information System 10-Item Global Health Scale (PROMIS-10) Score from Baseline
Health status will be assessed at baseline, at cycle 3 of chemotherapy, at 3 and 12 months post-chemotherapy, and annually through 5 years, with chemotherapy administered for up to 18 weeks.
Change in N-terminal pro-B-type Natriuretic Peptide (NT-proBNP)
Biomarkers will be measured at baseline prior to chemotherapy, every 2 cycles during chemotherapy, and at 3 and 12 months post-chemotherapy to assess treatment-related changes over time, with chemotherapy administered for up to 18 weeks.
- +7 more secondary outcomes
Study Arms (6)
Arm A: Dexrazoxane + Doxorubicin + RCHOP
EXPERIMENTALParticipants will be randomized in 1:1 ratio and stratified by cancer stage and enrolling site to this group and will complete: * Baseline visit * Cycle 1 through End of Treatment (21 day cycles): * Day 1: predetermined dose of Dexrazoxane 1x daily * Day 1: predetermined dose of Doxorubicin 1x daily * Standard of care R-CHOP per protocol * 3 and 12 month follow up post-standard of care treatment completion * Long term follow up: annually from year 2 - 5
Arm B: Dexrazoxane Placebo + Liposomal Doxorubicin + RCHOP
PLACEBO COMPARATORParticipants will be randomized in 1:1 ratio and stratified by cancer stage and enrolling site to this group and will complete: * Baseline visit * Cycle 1 through End of Treatment (21 day cycles): * Day 1: predetermined dose of Dexrazoxane placebo 1x daily * Day 1: predetermined dose of Liposomal Doxorubicin 1x daily * Standard of care R-CHOP per protocol * 3 and 12 month follow up post-standard of care treatment completion * Long term follow up: annually from year 2 - 5
Arm C: Dexrazoxane + Doxorubicin + pola-R-CHP
EXPERIMENTALParticipants will be randomized in 1:1 ratio and stratified by cancer stage and enrolling site to this group and will complete: Baseline visit * Cycle 1 through End of Treatment (21 day cycles): * Day 1: predetermined dose of Dexrazoxane 1x daily * Day 1: predetermined dose of Doxorubicin 1x daily * Standard of care pola-R-CHP per protocol * 3 and 12 month follow up post-standard of care treatment completion * Long term follow up: annually from year 2 - 5
Arm D: Dexrazoxane Placebo + Liposomal Doxorubicin + pola-R-CHP
PLACEBO COMPARATORParticipants will be randomized in 1:1 ratio and stratified by cancer stage and enrolling site to this group and will complete: * Baseline visit * Cycle 1 through End of Treatment (21 day cycles): * Day 1: predetermined dose of Dexrazoxane placebo 1x daily * Day 1: predetermined dose of Liposomal Doxorubicin 1x daily * Standard of care pola-R-CHP per protocol * 3 and 12 month follow up post-standard of care treatment completion * Long term follow up: annually from year 2 - 5
Arm E: Observational R-CHOP
OTHERParticipants meeting inclusion but not all exclusion criteria, or who decline randomization, may enroll in an observational cohort for data and biospecimen collection and will complete the following: * Baseline visit with assessments and questionnaires * Cycle 1 through End of Treatment (21 day cycles): * Day 1: assessments and questionnaires * Standard of care R-CHOP * 3 and 12 month follow up post-treatment completion * Long term follow up: annually from year 2 - 5, in-person or virtually
Arm F: Observational pola-R-CHP
OTHERParticipants meeting inclusion but not all exclusion criteria, or who decline randomization, may enroll in an observational cohort for data and biospecimen collection and will complete the following: * Baseline visit with assessments and questionnaires * Cycle 1 through End of Treatment (21 day cycles): * Day 1: assessments and questionnaires * Standard of care pola-R-CHP * 3 and 12 month follow up post-treatment completion * Long term follow up: annually from year 2 - 5, in-person or virtually
Interventions
Topoisomerase II Inhibitor, single-dose vial, via intravenous infusion per protocol.
Dexrazoxane placebo via intravenous infusion per protocol.
Topoisomerase II Inhibitors, single-dose vial, via intravenous infusion per protocol.
Topoisomerase II Inhibitors, single-dose vial, via intravenous infusion per protocol.
Lymphodepleting chemotherapy, multi-dose vial, via intravenous infusion per standard of care.
vinca alkaloid, single-dose vial, via intravenous infusion per standard of care.
Glucocorticoid, tablet taken orally per standard of care.
Anti-CD20 antibody, single-use vials, via intravenous infusion per standard of care.
CD79b-directed antibody-drug conjugate, single-dose vial, via intravenous infusion per standard of care.
Eligibility Criteria
You may qualify if:
- Participants must have histologically confirmed diffuse large B-cell lymphoma, histologically transformed large B cell lymphoma from a prior indolent lymphoma, or other high-grade B-cell lymphoma for which R-CHOP or pola-R-CHP are planned. Any cancer stage is permitted.
- Participants must not have received any prior chemotherapy for this malignancy. Pre-phase steroids are allowed. Prior treatment for a different malignancy is allowed, including prior treatment for indolent lymphoma.
- Age ≥18 years. Diffuse large B cell lymphoma is rare in participants \<18 years of age. The prevalence of HF prior to chemotherapy is also exceedingly rare in participants \<18 years of age; therefore, participants \<18 years of age are excluded from this study.
- Participants must have ONE or more of the following risk factors for HF events with anthracycline-containing chemotherapy
- LVEF 30-50% on most recent echocardiogram with or without HF history
- LVEF 50% with a history of HF (i.e. HF with improved EF or HF with preserved EF).
- History of anthracycline exposure for different malignancy.
- Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
- Because dexrazoxane as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of chemotherapy administration.
- Ability to understand and the willingness to sign a written informed consent document.
You may not qualify if:
- New York Heart Association (NYHA) Class III or IV exertional dyspnea. The symptoms should be attributed to HF and not due to lymphoma, anemia, arthritis or other causes per the assessment of the treating clinician or study investigator. NYHA Class III defined as: "Marked limitations with less than ordinary activity such as walking short distances or climbing a few stairs" and NYHA Class IV defined as: "Inability to carry out any activity without discomfort. Symptoms are present at rest and if any physical activity is undertaken the symptoms are increased." (see Appendix A for NYHA Classification).
- LVEF \<30% on most recent echocardiogram. Patients with prior LVEF \<30% with improvement to \>30% on most recent echocardiogram are eligible.
- Meeting criteria for frailty according to the simplified geriatric assessment (see Appendix A for the simplified geriatric assessment criteria).
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to any agents used in study.
- Presence of central nervous system involvement
- Presence of concurrent genetic rearrangements of the MYC and BCL2 genes, so called "double-hit" large-cell lymphoma who are not deemed eligible for intensified induction chemotherapy such as dose adjusted EPOCH-R by their treating physician can be enrolled
- Ineligible for R-CHOP or pola-R-CHP because of liver disease per institutional policies
- Patients with planned dose reductions from the first cycle ie R-mini-CHOP will be excluded
- There are no contraindicated medications. Caution and monitoring are advised with medications that can cause myelosuppression.
- Patients with positive Hepatitis B core antibody can be enrolled if they have negative viral load and can be maintained on antiviral prophylaxis
- Patients with HIV can be enrolled if they have anti-retroviral therapy options without drug-drug interactions with the cancer treatment, agree to take anti-retroviral therapy and do not have uncontrolled opportunistic infections.
- Pregnant women are excluded from this study because dexrazoxane and liposomal doxorubicin are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with dexrazoxane and liposomal doxorubicin, breastfeeding should be discontinued if the mother is treated with dexrazoxane and liposomal doxorubicin. These potential risks may also apply to other agents used in this study.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jenica Upshaw, MD, MSc
Beth Israel Deaconess Medical Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Double Blind
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
June 12, 2026
First Posted
June 17, 2026
Study Start (Estimated)
October 2, 2026
Primary Completion (Estimated)
December 31, 2030
Study Completion (Estimated)
December 31, 2035
Last Updated
June 17, 2026
Record last verified: 2026-06
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- Data can be shared no earlier than 1 year following the date of publication
The Harvard Cancer Consortium encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.