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Diffuse Large B-cell Lymphoma (DLBCL)Phase 2NCT07654426

The CARDIOPROTECT Trial

A Phase 2 study testing Dexrazoxane, Doxorubicin and Liposomal Doxorubicin in people with Diffuse Large B-cell Lymphoma (DLBCL) and Cardiotoxicity, run by Beth Israel Deaconess Medical Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Dexrazoxane, Doxorubicin and Liposomal Doxorubicin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
60 participants
Where
1 siteUnited States
Study dates
31 Aug 2026to 31 Dec 2035
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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.

Who cannot join

  • 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
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  • 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.
  • Eligibility for observational arm of the study. The above inclusion and exclusion criteria are for the randomized trial. Patients who meet the inclusion criteria but have one or more exclusion criterion are eligible to participate in the observational arm of the study. In addition, patients who meet all eligibility criteria for the randomized trial but decline participation in the randomized trial are also eligible to participate in the observational arm of the study.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Jenica Upshaw, MD, MSc contact

(617) 667-8800

jupshaw@bidmc.harvard.edu

United States1 site, 1 recruiting

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

    Jenica Upshaw, MD, MSc, (617) 667-8800, jupshaw@bidmc.harvard.edu

    Recruiting

Other trials in United States

About this study

Official title: 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

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
Read the detailed description

This phase II, multicenter, randomized, double-blind, double-dummy 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.

Participants will be assigned by the study doctor to standard of care R-CHOP or standard of care pola-R-CHP therapy regimens.

R-CHOP Participants will be randomized into 1 of 2 study groups: Group A: Dexrazoxane, cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab versus Group B: Placebo, cyclophosphamide, liposomal doxorubicin, vincristine, prednisone, rituximab. Participants will have an equal chance of being placed into one of those study groups.

Pola-R-CHP participants will be randomized into 1 of 2 study groups: Group C: Dexrazoxane, cyclophosphamide, doxorubicin, polatuzumab vedotin-piiq, prednisone, rituximab versus Group D: Placebo, cyclophosphamide, liposomal doxorubicin, polatuzumab vedotin-piiq, prednisone, rituximab. Participants will have an equal chance of being placed into one of those study groups.

Randomization means a participant is placed into a study group by chance. Neither a participant or the study doctor will choose or know what group a participant is placed in. This is called a "double-blind" study.

The research study procedures include screening for eligibility, in-clinic visits, questionnaires, blood tests, urine tests, electrocardiograms (ECGs), and echocardiograms (ECHO).

The U.S. Food and Drug Administration (FDA) has not approved dexrazoxane for DLBCL.

The FDA has not approved liposomal doxorubicin for DLBCL. The FDA has approved all the drugs in R-CHOP as a treatment option for DLBCL. The FDA has approved all the drugs in pola-R-CHP as a treatment option for DLBCL It is expected that about 60 people will take part in this research study. The National Cancer Institute is sponsoring this study by providing funding.

Being tested
Dexrazoxane, Dexrazoxane placebo, Doxorubicin, Liposomal Doxorubicin, Cyclophosphamide
Keywords
Diffuse Large B-cell Lymphoma (DLBCL), High Risk for Heart Failure Events, Cardiotoxicity, Lymphoma, Stage B Heart Failure, Stage C Heart Failure, Left ventricular ejection fraction (LVEF) decline
Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Cardiotoxicity, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DexrazoxaneDrug

    Also called C11H16N4O4

    Topoisomerase II Inhibitor, single-dose vial, via intravenous infusion per protocol.

  • Dexrazoxane placeboDrug

    Dexrazoxane placebo via intravenous infusion per protocol.

  • DoxorubicinDrug

    Also called doxorubicin hydrochloride, C27H29NO11•HCL, ADRIAMYCIN, FI-106

    Topoisomerase II Inhibitors, single-dose vial, via intravenous infusion per protocol.

  • Liposomal DoxorubicinDrug

    Also called doxorubicin hydrochloride, Caelyx, Doxil, TLC-DOXO, PLD, Pegylated Liposomal Doxorubicin, TLC D-99, ATI-0918

    Topoisomerase II Inhibitors, single-dose vial, via intravenous infusion per protocol.

  • CyclophosphamideDrug

    Also called C7H15Cl2N2O2P•H2O, Cytoxan, Cyclophosphamide-OE

    Lymphodepleting chemotherapy, multi-dose vial, via intravenous infusion per standard of care.

  • VincristineDrug

    Also called Vincristine Sulfate, C46H56N4O10

    vinca alkaloid, single-dose vial, via intravenous infusion per standard of care.

  • PrednisoneDrug

    Also called C21H26O5

    Glucocorticoid, tablet taken orally per standard of care.

  • RituximabDrug

    Also called Riabni, Rituxan, Ruxience, Truxima, ABP 798, IDEC-C2B8, PF-05280586

    Anti-CD20 antibody, single-use vials, via intravenous infusion per standard of care.

  • Polatuzumab VedotinDrug

    Also called Polatuzumab Vedotin-piiq

    CD79b-directed antibody-drug conjugate, single-dose vial, via intravenous infusion per standard of care.

Study groups in NCT07654426
Study groupRoleWhat they receive
Arm A: Dexrazoxane + Doxorubicin + RCHOPExperimentalParticipants 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
Receives: Drug: Dexrazoxane; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Prednisone; Drug: Rituximab
Arm B: Dexrazoxane Placebo + Liposomal Doxorubicin + RCHOPPlacebo 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
Receives: Drug: Dexrazoxane placebo; Drug: Liposomal Doxorubicin; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Prednisone; Drug: Rituximab
Arm C: Dexrazoxane + Doxorubicin + pola-R-CHPExperimentalParticipants 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
Receives: Drug: Dexrazoxane; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Prednisone; Drug: Rituximab; Drug: Polatuzumab Vedotin
Arm D: Dexrazoxane Placebo + Liposomal Doxorubicin + pola-R-CHPPlacebo 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
Receives: Drug: Dexrazoxane placebo; Drug: Liposomal Doxorubicin; Drug: Cyclophosphamide; Drug: Prednisone; Drug: Rituximab; Drug: Polatuzumab Vedotin
Arm E: Observational R-CHOPOtherParticipants 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
Receives: Drug: Dexrazoxane; Drug: Dexrazoxane placebo; Drug: Doxorubicin; Drug: Liposomal Doxorubicin; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Prednisone; Drug: Rituximab
Arm F: Observational pola-R-CHPOtherParticipants 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
Receives: Drug: Dexrazoxane placebo; Drug: Doxorubicin; Drug: Liposomal Doxorubicin; Drug: Cyclophosphamide; Drug: Prednisone; Drug: Rituximab; Drug: Polatuzumab Vedotin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: 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)

  1. Time to First Heart Failure (HF) Events

    Time to first HF events is defined as the time from randomization to the first adjudicated heart failure event, including HF-related hospitalizations, emergency department visits, or urgent outpatient visits for worsening HF, or censoring at last follow-up, study withdrawal, based on a cause-specific hazard model.

    Measured: Up to 5 years

  2. Time to Recurrent Heart Failure (HF) Events

    Time to recurrent HF events is defined as the time from randomization to all adjudicated heart failure event, including HF-related hospitalizations, emergency department visits, or urgent outpatient visits for worsening HF, or censoring at last follow-up, study withdrawal, based on Andersen-Gill or Lin-Wei-Ying-Yang (LWYY) models.

    Measured: Up to 5 years

  3. Changes in 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12) Score from Baseline

    This endpoint evaluates score changes in self-reported health status using the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12), which ranges from 0 to 70, with higher scores indicating better health status. Clinically meaningful changes are defined as 5-, 10-, and 20-point thresholds.

    Measured: 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.

  4. Changes in Patient-Reported Outcomes Measurement Information System 10-Item Global Health Scale (PROMIS-10) Score from Baseline

    This endpoint evaluates changes in self-reported global health status using the 10-item PROMIS Global scale (PROMIS-10), in which the first 9 items are scored 1-5 and the last item is scored 0-10, with higher scores indicating better overall physical and mental health.

    Measured: 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.

  5. Change in N-terminal pro-B-type Natriuretic Peptide (NT-proBNP)

    NT-proBNP is measured in picograms per milliliter (pg/mL) using established laboratory methods. Values are collected to assess changes in neurohormonal activation.

    Measured: 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.

  6. Change in High-Sensitivity Troponin

    High-sensitivity troponin is measured in nanograms per liter (ng/L) using established

    Measured: 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. Median Progression-Free Survival (PFS)

    PFS based on Kaplan-Meier method is defined as from date of registration to date of first observation of progressive disease according to the 2014 Lugano classification, or death due to any cause. Participants last known to be alive and without report of progression are censored at date of last contact.

    Measured: Up to 5 years

  8. Time to First Cardiovascular (CV) Event

    Time to first CV event is defined as the time from randomization to the first adjudicated major cardiovascular event, including acute coronary syndrome, ischemic or hemorrhagic stroke, atrial fibrillation or atrial flutter, or ventricular tachycardia, with death treated as a competing risk.

    Measured: Up to 5 years

  9. Median Overall Survival (OS)

    OS based on Kaplan-Meier method is defined as the time from randomization (or registration) to death due to any cause or censored at date last known alive.

    Measured: Up to 5 years

  10. Cause-Specific Mortality

    Cause-specific mortality will be analyzed using a cause-specific proportional hazards model, with deaths from other causes treated as competing risks, to estimate the relative effect of treatment on cause-specific mortality.

    Measured: Up to 5 years

  11. Grade 2 or Higher Adverse Event (AE) Rate

    Grade 2 or higher AE rate is defined as the proportion of participants who experience grade 2 or higher AE. AE will be summarized and graded based on CTCAE 5.0.

    Measured: Adverse events will be monitored up to 12 months after completion of chemotherapy, with chemotherapy administered for up to 18 weeks.

  12. Grade 3 or Higher Adverse Event (AE) Rate

    Grade 3 or higher AE rate is defined as the proportion of participants who experience grade 3 or higher AE. AE will be summarized and graded based on CTCAE 5.0.

    Measured: Adverse events will be monitored up to 12 months after completion of chemotherapy, with chemotherapy administered for up to 18 weeks.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jun 2026
  2. Study start31 Aug 2026 (estimated)
  3. Primary completion31 Dec 2030 (estimated)
  4. Study completion31 Dec 2035 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07654426
Sponsor's protocol ID
25-814
Status last verified
Jul 2026
First submitted
12 Jun 2026
Last updated
27 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dexrazoxane, Doxorubicin and Liposomal Doxorubicin in people with Diffuse Large B-cell Lymphoma (DLBCL) and Cardiotoxicity, run by Beth Israel Deaconess Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 27 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Jenica Upshaw, MD, MSc ((617) 667-8800, jupshaw@bidmc.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Left Ventricular Ejection Fraction (LVEF) (time frame: LVEF will be assessed by echocardiography 3 months after completion of front-line chemotherapy, with chemotherapy administered for up to 18 weeks.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07654426.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2026.

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