DLBCL - Diffuse Large B Cell Lymphoma Clinical Trial
Official title:
ANTICIPATE: Prevention of ANThracycline-Induced Cardiac Dysfunction by Dexrazoxane In PATients With diffusE Large B-cell Lymphoma: a Phase III National Multicenter Prospective Randomized Open-label Trial
Patients treated for DLBCL are at high risk of developing AICD. This adverse event is characterized by irreversible damage to the heart muscle with a loss of cardiomyocytes and subsequent decline in cardiac pumping capacity. Thereby patients treated for this malignancy are at double the risk of developing symptomatic heart failure / cardiomyopathy when compared to the general population. This corresponds to a cumulative incidence of 5-10% within 5-years after receiving R-CHOP. In the elderly, an incidence of 26% has been reported after 8-years of follow-up. Among patients who die in complete remission, heart failure has been described to be one of the most important causes of death. ANTICIPATE aims to evaluate if dexrazoxane can prevent AICD in DLBCL patients and identify those at highest risk of AICD. Of all patients treated with anthracyclines in a first-line setting, DLBCL patients were chosen for this trial for two primary reasons. Firstly, these patients have a favourable oncological prognosis with a 5-year relative survival in the Netherlands of 64-78% in those aged 18-74 years increasing the importance of preventing long-term toxicity. Secondly, the cumulative anthracycline dose used for the treatment of DLBCL is higher than the dose used in breast cancer. The cumulative anthracycline dose is the most important risk factor for AICD known.
HO170 DLBCL-ANTICIPATE: "Prevention of ANThracycline-Induced Cardiac dysfunction by dexrazoxane In PATients with diffusE large B-cell lymphoma" is a national randomized controlled trial that will be conducted across 25 Dutch hospitals. This study will include adult patients with DLBCL in which first-line treatment with 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) is planned (cumulative doxorubicin dose 300 mg/m2). In this trial, we have chosen to include patients with a normal cardiac function before chemotherapy because cardiac dysfunction is a contra-indication for administration of anthracyclines. A total of 324 DLBCL patients will prior to treatment be randomized in a 1:1 ratio to either (1) intravenous dexrazoxane administration in a 10:1 dexrazoxane:doxorubicin ratio prior to each doxorubicin infusion or (2) no cardioprotective treatment (current standard of care). Due to the low pH of the dexrazoxane solution that would jeopardize the blinding no placebo is used. Cardiac function will be screened with echocardiography prior to the initiation of chemotherapy and followed-up at 4- and 12-months post randomization. The primary end point of the study will be the incidence of AICD, defined as a left ventricular ejection fraction (LVEF) decline of ≥10 percentage points from baseline and below 50% (normal reference value for two-dimensional (2D) echocardiography). The secondary endpoint will be the percentage of patients with complete metabolic remission (CMR) after R-CHOP chemotherapy, to reassure that dexrazoxane does not influence the antineoplastic efficacy of doxorubicin. To declare ANTICIPATE successful, the trial must show both the superiority of addition of dexrazoxane on the primary endpoint and non-inferiority on the secondary endpoint. Deep-phenotyping of patient- and treatment-related factors will be performed to evaluate their prognostic value. ;