Phase 2 dexrazoxane Top2β cardioprotectant vs liposomal doxorubicin anthracycline in DLBCL

This Phase 2 randomized, double-blind, double-dummy CARDIOPROTECT trial tests two strategies to reduce anthracycline-related heart failure events in newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients at high cardiac risk while preserving curative lymphoma outcomes. Participants receiving standard first-line immunochemotherapy (either R-CHOP or polatuzumab vedotin–R-CHP) are randomized to (1) dexrazoxane, a small-molecule cardioprotectant that chelates iron and functionally reduces doxorubicin-induced Top2β–mediated DNA damage in cardiomyocytes, paired with conventional doxorubicin, or (2) dexrazoxane placebo paired with liposomal doxorubicin, which encapsulates doxorubicin to alter tissue distribution and may lower myocardial exposure. The sponsor is Beth Israel Deaconess Medical Center (Beth Israel Lahey Health); the commercial angle is a head-to-head, regimen-embedded cardio-oncology comparison that could change how high-risk patients receive anthracyclines without defaulting to less effective substitutes. Today, front-line DLBCL care is typically curative-intent R-CHOP, and for many higher-risk patients polatuzumab vedotin with R-CHP is used; both still rely on an anthracycline backbone, making cardioprotection a key practical barrier for patients with reduced LVEF, prior heart failure, or prior anthracycline exposure.