Neoplasms

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Symptoms and General Pathology

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Heart Failure

Lymphoma

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Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

B-cell Lymphoma

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Antineoplastic Agents

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All Drugs and Chemicals

Anti-Inflammatory Agents

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Gastrointestinal Agents

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Anti-Infective Agents

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

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Vincristine

Prednisolone

Lenalidomide

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

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Dexrazoxane

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Immunologic Factors

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Alkylating Agents

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Enzyme Inhibitors

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Antimitotic Agents

Angiogenesis Inhibitors

Growth Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Protective Agents

Standard R-CHOP 21 treatment regimen:

6 cycles R-CHOP 21 (rituximab\*, cyclophosphamide, doxorubicin, vincristine, prednisolone)

\*The use of a biosimilar is allowed.

Addition of the cardioprotectant dexrazoxane to the R-CHOP 21 regimen:

R-CHOP21 (rituximab\*, cyclophosphamide, doxorubicin, vincristine, prednisolone plus dexrazoxane).

\*The use of a biosimilar is allowed.

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.

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

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

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

Pegfilgrastim

A. van Rhenen, MD

M.P.M. Linschoten, MD

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.

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

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

According to the current publication policy the protocol and Statistical Analysis Plan (SAP) will be shared. The Principal Investigators can be contacted for IPD sharing after the publication of the study results. According to the 'HOVON Sample and/or Data request Form' the HOVON director; chair of the lymphoma working group, the study PI and Coordinating Investigator should approve data/sample sharing.

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

Major Adverse Cardiovascular Events (MACE) at 1-, 2-, 5- and 10-years.

The incidence of AICD (measured with 2D) within 12 months after registration.

Complete metabolic remission (CMR) on 18F-FDG PET-CT at end of treatment 6-8 weeks after completion of 6x R-CHOP21.

Progression-free survival (PFS) at 12-months.

LVEF (2D and 3D) and global longitudinal strain (GLS) at end of treatment and 12-months after start of treatment.

Release of cardiac biomarkers. At entry, after every cyle of R-CHOP, at EOT and FU. CK (if available); CK-MB (if available) \& (hs)Troponin T/I (assay according to local practice).

To analyse the impact of the addition of dexrazoxane on QoL via validated questionaires such as QLQ-C30, NHL-HG29, PRO-CTCAE.

UMC Utrecht

Amsterdam University Medical Centers

The Dutch Network for Cardiovascular Research (WCN)

Stichting Hemato-Oncologie voor Volwassenen Nederland

Spots Global Cancer Trial Database for r2chop

Every month we try and update this database with for r2chop cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for r2chop

Every month we try and update this database with for r2chop cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for r2chop cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.