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.
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
Testicular DLBCL;
Primary mediastinal B-cell lymphoma;
Epstein-Barr virus (EBV) post-transplant lymphoproliferative disorder;
Any prior malignancy or present malignancy other than DLBCL that required or requires systemic therapy. Prior surgery or local radiotherapy is allowed in case the heart has not been exposed.
Parallel
Dexrazoxane
DrugDay 1 Cycle 1-6: Dexrazoxane 500 mg/m2 (iv) will be given 30 minutes before doxorubicin infusion and should be infused during 15 minutes.
Rituximab
DrugDay 1 Cycle 1-6: 375 mg/m2 (iv)
Cyclophosphamide
DrugDay 1 Cycle 1-6: 750 mg/m2 (iv)
Doxorubicin
DrugDay 1 Cycle 1-6: 50 mg/m2 (iv)
Vincristine
DrugDay 1 Cycle 1-6: 1.4 mg/m2 (max 2 mg) (iv)
Prednisolone
DrugDay 1-5 Cycle 1-6: 100 mg (oral)
Lenalidomide
DrugDay 1-14 Cycle 1-6: 15 mg day (oral) Only in case of a double hit lymphoma.
Pegfilgrastim
Drug6 mg (1 dose per cycle) in case of neutropenia. Pegfilgastim is mandatory in patients that receive R2-CHOP21.
The incidence of AICD.
The incidence of AICD (measured with 2D) within 12 months after registration is reported in the eCRF.
Complete Metabolic Remission.
Complete metabolic remission (CMR) on 18F-FDG PET-CT at end of treatment 6-8 weeks after completion of 6x R-CHOP21 is reported in the eCRF.
Overall survival (OS).
Overall survival (OS) at 12-months is reported in the eCRF.
Progression-free survival.
Progression-free survival (PFS) at 12-months is reported in the eCRF.
LVEF and global longitudinal strain (GLS).
LVEF (2D and 3D) and global longitudinal strain (GLS) at end of treatment and 12-months after start of treatment is reported in the eCRF.
Safety and toxicity.
Safety and toxicity as defined by type, frequency and severity of adverse events as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Secondary malignancies.
Incidence of secondary malignancies.
Major Adverse Cardiovascular Events.
Major Adverse Cardiovascular Events (MACE) at 1-, 2-, 5- and 10-years.
Click on the lead sponsor to view all of their trials.
Stichting Hemato-Oncologie voor Volwassenen Nederland
Lead sponsor
UMC Utrecht
Collaborator
Amsterdam UMC, location VUmc
Collaborator
The Dutch Network for Cardiovascular Research (WCN)
Collaborator
