Prevention of Anthracycline-Induced Cardiac Dysfunction With Dexrazoxane in Patients With Diffuse Large-B Cell Lymphoma

Summary

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.

Conditions

• DLBCL - Diffuse Large B Cell Lymphoma

Interventions

DRUG

Dexrazoxane

Day 1 Cycle 1-6: Dexrazoxane 500 mg/m2 (iv) will be given 30 minutes before doxorubicin infusion and should be infused during 15 minutes.

DRUG

Rituximab

Day 1 Cycle 1-6: 375 mg/m2 (iv)

DRUG

Cyclophosphamide

Day 1 Cycle 1-6: 750 mg/m2 (iv)

DRUG

Doxorubicin

Day 1 Cycle 1-6: 50 mg/m2 (iv)

DRUG

Vincristine

Day 1 Cycle 1-6: 1.4 mg/m2 (max 2 mg) (iv)

DRUG

Prednisolone

Day 1-5 Cycle 1-6: 100 mg (oral)

DRUG

Lenalidomide

Day 1-14 Cycle 1-6: 15 mg day (oral) Only in case of a double hit lymphoma.

DRUG

Pegfilgrastim

6 mg (1 dose per cycle) in case of neutropenia. Pegfilgastim is mandatory in patients that receive R2-CHOP21.

Sponsors & Collaborators

• UMC Utrecht

  collaborator OTHER

• Amsterdam University Medical Centers

  collaborator UNKNOWN

• The Dutch Network for Cardiovascular Research (WCN)

  collaborator UNKNOWN

• Stichting Hemato-Oncologie voor Volwassenen Nederland

  lead OTHER

Principal Investigators

• A. van Rhenen, MD · UMC Utrecht

• M.P.M. Linschoten, MD · Amsterdam UMC

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-08-15

Primary Completion

2028-12-15

Completion

2028-12-15

Countries

• Netherlands

Study Locations