The CARDIOPROTECT Trial

Inclusion Criteria:

* 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

  1. LVEF 30-50% on most recent echocardiogram with or without HF history
  2. LVEF 50% with a history of HF (i.e. HF with improved EF or HF with preserved EF).
  3. 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.

Exclusion Criteria:

* 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.
* 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.