Health TrialsbyHealthPanel

The CARDIOPROTECT Trial

ConditionsDiffuse Large B-cell Lymphoma (DLBCL)CardiotoxicityLymphoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorBeth Israel Deaconess Medical Center

About this 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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Dexrazoxane

    Drug

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

  • Dexrazoxane placebo

    Drug

    Dexrazoxane placebo via intravenous infusion per protocol.

  • Doxorubicin

    Drug

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

  • Liposomal Doxorubicin

    Drug

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

  • Cyclophosphamide

    Drug

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

  • Vincristine

    Drug

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

  • Prednisone

    Drug

    Glucocorticoid, tablet taken orally per standard of care.

  • Rituximab

    Drug

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

  • Polatuzumab Vedotin

    Drug

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

Treatment groups

60 Participants
are divided into 6 treatment groups

6

Treatment groups

See each treatment group below.

Group A: Arm A: Dexrazoxane + Doxorubicin + RCHOPExperimental treatment 6 interventions
Group B: Arm B: Dexrazoxane Placebo + Liposomal Doxorubicin + RCHOPPlacebo comparator 6 interventions
Group C: Arm C: Dexrazoxane + Doxorubicin + pola-R-CHPExperimental treatment 6 interventions
Group D: Arm D: Dexrazoxane Placebo + Liposomal Doxorubicin + pola-R-CHPPlacebo comparator 6 interventions
Group E: Arm E: Observational R-CHOPOther 8 interventions
Group F: Arm F: Observational pola-R-CHPOther 7 interventions

Trial outcomes

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).

Time frame
LVEF will be assessed by echocardiography 3 months after completion of front-line chemotherapy, with chemotherapy administered for up to 18 weeks.

Secondary outcomes

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.

Time frame
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.

Time frame
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.

Time frame
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.

Time frame
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.

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Beth Israel Deaconess Medical Center

Lead sponsor

Source ClinicalTrials.gov
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