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.
• Untreated patients with a confirmed histologic diagnosis of CD20+ DLBCL according to WHO classification 2022:
‣ DLBCL, not otherwise specified (NOS)
⁃ High-grade B-cell lymphoma NOS
⁃ High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 translocation when DA-EPOCH-R is not an option. R2- CHOP is allowed.
⁃ Follicular lymphoma
⁃ T-cell/histiocyte-rich B cell lymphoma (THRBCL)
• Note: Transformed, previously untreated lymphoma is allowed.
• Note: 5-day treatment of dexamethasone 15 mg/day or prednisone 100 mg/day or local radiotherapy in order to control life-threatening/invalidating tumor related symptoms is allowed.
• Note: It is allowed to start with a first cycle of R-CHOP21 pending the FISH results.
• Planned treatment with 6 R-CHOP21. The following regimens are also allowed:
‣ Treatment with reversed R-CHOP21
⁃ Treatment with R2-CHOP21 (6 R-CHOP21 + lenalidomide 15 mg day 1-14) in case of double hit lymphoma
⁃ Two additional administrations of rituximab after 6 cycles of R-CHOP21
⁃ High dosis MTX and/or MTX-it for CNS prophylaxis
• Ann Abor stages II-IV and stage I if the treatment plan is 6 R-CHOP21 in case of bulky disease (defined as a ≥10 cm mass);
• Age ≥ 18 years;
• WHO performance status ≤ 2, WHO 3 performance status is allowed when considered directly related to the DLBCL;
• Negative pregnancy test at study entry for women of childbearing potential;
• Female patient is either post-menopausal for at least 1 year before the screening visit or surgically sterile or if of childbearing potential, agrees to practice two effective methods of contraception, at the same time, from the time of signing the informed consent through at least 12 months after the last dose of protocol treatment, or agrees to completely abstain from heterosexual intercourse;
• Male patient, even if surgically sterilized, (i.e., status post vasectomy) agrees to practice effective barrier contraception during the entire study period and through 12 months after the last dose of protocol treatment, or agrees to completely abstain from heterosexual intercourse;
• Patient is able to adhere to the study visit schedule and other protocol requirements;
⁃ Written informed consent.