Prevention of Anthracycline-Induced Cardiac Dysfunction With Dexrazoxane in Patients With Diffuse Large-B Cell Lymphoma
HO170DLBCL
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
2 other identifiers
interventional
324
1 country
25
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Aug 2024
Typical duration for phase_3
25 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 11, 2024
CompletedFirst Posted
Study publicly available on registry
January 23, 2024
CompletedStudy Start
First participant enrolled
August 15, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 15, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 15, 2028
January 5, 2026
October 1, 2025
4.3 years
January 11, 2024
January 2, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
The incidence of AICD.
The incidence of AICD (measured with 2D) within 12 months after registration.
12 months after LPI
Secondary Outcomes (7)
Complete Metabolic Remission.
12 months after LPI
Overall survival (OS).
12 months after LPI
Progression-free survival.
12 months after LPI
LVEF and global longitudinal strain (GLS).
12 months after LPI
NYHA.
12 months after LPI
- +2 more secondary outcomes
Other Outcomes (3)
Safety and toxicity.
12 months after LPI
Secondary malignancies.
12 months after LPI
Major Adverse Cardiovascular Events.
1- 2-, 5- and 10 years
Study Arms (2)
Arm A
EXPERIMENTALStandard R-CHOP 21 treatment regimen: 6 cycles R-CHOP 21 (rituximab\*, cyclophosphamide, doxorubicin, vincristine, prednisolone) \*The use of a biosimilar is allowed.
Arm B -
EXPERIMENTALAddition 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.
Interventions
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.
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.
Eligibility Criteria
You may qualify if:
- 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);
- +7 more criteria
You may not qualify if:
- Any of the following B-cell lymphomas according to WHO classification 2022:
- o Central Nervous System involvement by DLBCL;
- Note: high CNS-IPI is allowed
- 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.
- Patients requiring treatment with mini-R-CHOP
- Pre-existing cardiac disease including:
- LVEF \<50% measured with echocardiography (2D or 3D)
- Symptomatic heart failure (NYHA ≥II) or hospitalization for heart failure in the last year;
- Refractory anginal symptoms
- Cardiac arrhythmias not controlled with optimal medical treatment, in case of atrial fibrillation the ventricular response needs to be \<110/min;
- Significant valvular dysfunction on echocardiography;
- Non-ischemic cardiomyopathy
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- The Dutch Network for Cardiovascular Research (WCN)collaborator
- Stichting Hemato-Oncologie voor Volwassenen Nederlandlead
- UMC Utrechtcollaborator
- Amsterdam University Medical Centerscollaborator
Study Sites (25)
NL-Den Bosch-JBZ
's-Hertogenbosch, Netherlands
NL-Almelo-ZGTALMELO
Almelo, Netherlands
NL-Amstelveen-AMSTELLAND
Amstelveen, Netherlands
NL-Apeldoorn-GELREAPELDOORN
Apeldoorn, Netherlands
NL-Arnhem-RIJNSTATE
Arnhem, Netherlands
NL-Breda-AMPHIA
Breda, Netherlands
NL-Delft-RDGG
Delft, Netherlands
NL-Dordrecht-ASZ
Dordrecht, Netherlands
NL-Eindhoven-CATHARINA
Eindhoven, Netherlands
NL-Eindhoven-MAXIMAMC
Eindhoven, Netherlands
NL-Goes-ADRZ
Goes, Netherlands
NL-Groningen-MARTINI
Groningen, Netherlands
NL-Harderwijk-STJANSDALHARDERWIJK
Harderwijk, Netherlands
NL-Hilversum-TERGOOI
Hilversum, Netherlands
NL-Hoofddorp-SPAARNEGASTHUIS
Hoofddorp, Netherlands
NL-Nieuwegein-ANTONIUS
Nieuwegein, Netherlands
NL-Nijmegen-CWZ
Nijmegen, Netherlands
NL-Rotterdam-IKAZIA
Rotterdam, Netherlands
NL-Schiedam-FRANCISCUSVLIETLAND
Schiedam, Netherlands
NL-Sittard-ZUYDERLAND MC
Sittard, Netherlands
NL-Sneek-ANTONIUSSNEEK
Sneek, Netherlands
NL-Den Haag-HAGA
The Hague, Netherlands
NL-Utrecht-UMCUTRECHT
Utrecht, Netherlands
NL-Venlo-VIECURI
Venlo, Netherlands
NL-Zwolle-ISALA
Zwolle, Netherlands
Related Publications (1)
Linschoten M, Geels J, van Werkhoven E, Visser-Wisselaar H, Chamuleau MED, Teske AJ, Robbers L, Oerlemans S, Crommelin H, Breems-de Ridder M, Schut A, Asselbergs FW, van Rhenen A; HOVON 170 DLBCL - ANTICIPATE consortium. Rationale and design of the HOVON 170 DLBCL-ANTICIPATE trial: preventing anthracycline-induced cardiac dysfunction with dexrazoxane. Cardiooncology. 2025 Jan 28;11(1):8. doi: 10.1186/s40959-025-00303-y.
PMID: 39875951DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
A. van Rhenen, MD
UMC Utrecht
- PRINCIPAL INVESTIGATOR
M.P.M. Linschoten, MD
Amsterdam UMC
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 11, 2024
First Posted
January 23, 2024
Study Start
August 15, 2024
Primary Completion (Estimated)
December 15, 2028
Study Completion (Estimated)
December 15, 2028
Last Updated
January 5, 2026
Record last verified: 2025-10
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- After the publication of primary endpoint analysis.
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.