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Preventie van door antracycline geïnduceerde hartstoornissen met dexrazoxaan bij patiënten met diffuus groot-B-cellymfoom (HO170DLBCL)

18 september 2026 bijgewerkt door: Stichting Hemato-Oncologie voor Volwassenen Nederland

ANTICIPEREN: Preventie van door ANThracycline geïnduceerde hartdysfunctie door dexrazoxaan bij patiënten met diffuus groot B-cellymfoom: een fase III nationaal multicenter prospectief gerandomiseerd open-label onderzoek

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.

Studie Overzicht

Toestand

Werving

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Geschat)

324

Fase

  • Fase 3

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Contact Back-up

Studie Locaties

  • Nederland
      • 's-Hertogenbosch, Nederland
        • Werving
        • NL-Den Bosch-JBZ
      • Almelo, Nederland
        • Werving
        • NL-Almelo-ZGTALMELO
      • Amstelveen, Nederland
        • Werving
        • NL-Amstelveen-AMSTELLAND
      • Apeldoorn, Nederland
        • Werving
        • NL-Apeldoorn-GELREAPELDOORN
      • Arnhem, Nederland
        • Werving
        • NL-Arnhem-RIJNSTATE
      • Breda, Nederland
        • Werving
        • NL-Breda-AMPHIA
      • Delft, Nederland
        • Werving
        • NL-Delft-RDGG
      • Dordrecht, Nederland
        • Werving
        • NL-Dordrecht-ASZ
      • Eindhoven, Nederland
        • Werving
        • NL-Eindhoven-MAXIMAMC
      • Eindhoven, Nederland
        • Werving
        • NL-Eindhoven-CATHARINA
      • Goes, Nederland
        • Werving
        • NL-Goes-ADRZ
      • Groningen, Nederland
        • Werving
        • NL-Groningen-MARTINI
      • Harderwijk, Nederland
        • Werving
        • NL-Harderwijk-STJANSDALHARDERWIJK
      • Hilversum, Nederland
        • Werving
        • NL-Hilversum-TERGOOI
      • Hoofddorp, Nederland
        • Werving
        • NL-Hoofddorp-SPAARNEGASTHUIS
      • Nieuwegein, Nederland
        • Werving
        • NL-Nieuwegein-ANTONIUS
      • Nijmegen, Nederland
        • Werving
        • NL-Nijmegen-CWZ
      • Rotterdam, Nederland
        • Werving
        • NL-Rotterdam-IKAZIA
      • Schiedam, Nederland
        • Werving
        • NL-Schiedam-FRANCISCUSVLIETLAND
      • Sittard, Nederland
        • Werving
        • NL-Sittard-ZUYDERLAND MC
      • Sneek, Nederland
        • Werving
        • NL-Sneek-ANTONIUSSNEEK
      • The Hague, Nederland
        • Werving
        • NL-Den Haag-HAGA
      • Utrecht, Nederland
        • Werving
        • NL-Utrecht-UMCUTRECHT
      • Venlo, Nederland
        • Werving
        • NL-Venlo-VIECURI
      • Zwolle, Nederland
        • Werving
        • NL-Zwolle-ISALA

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

  1. 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.

  2. 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

  3. 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);

  4. Age ≥ 18 years;

  5. WHO performance status ≤ 2, WHO 3 performance status is allowed when considered directly related to the DLBCL;

  6. Negative pregnancy test at study entry for women of childbearing potential;

  7. 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;

  8. 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;

  9. Patient is able to adhere to the study visit schedule and other protocol requirements;

  10. Written informed consent.

Exclusion Criteria:

  1. 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;

  2. 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.

  3. Patients requiring treatment with mini-R-CHOP

  4. 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

  5. Non-diagnostic/poor transthoracic echocardiography imaging quality at baseline;

  6. Severe pulmonary dysfunction defined as breathlessness at rest (COPD GOLD III or IV), unless clearly related to DLBCL;

  7. Severe neurological or psychiatric disease;

  8. Inadequate hematological function (absolute Neutrophil Count (ANC) <1.0x109/L or platelets <75x109/L), unless clearly related to DLBCL;

  9. Significant hepatic dysfunction (serum bilirubin or transaminases ≥ 3 times the upper limit of normal) unless related to lymphoma infiltration of the liver;

  10. Active hepatitis B or C infection (serology testing is required at screening). Patients positive for hepatitis B surface antigen (HBsAg) regardless of antibody status or HBsAg negative but anti-HBc positive are only eligible if HBV-PCR is negative and patients are protected with lamuvidine or entecavir. Patients with positive hepatitis C serology are only eligible if HCV-(RNA) is confirmed negative;

  11. Significant renal dysfunction (creatinine clearance < 30 ml/min after rehydration) or requiring dialysis;

  12. Active uncontrolled fungal, bacterial and/or viral infection;

  13. Patient known to be HIV-positive;

  14. Breast-feeding female patients;

  15. Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule;

  16. Participation in another clinical trial with anti-cancer therapy or a cardiovascular drug.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Arm A

Standard R-CHOP 21 treatment regimen:

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

*The use of a biosimilar is allowed.
Geneesmiddel: Rituximab

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

Geneesmiddel: Cyclophosphamide

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

Geneesmiddel: Doxorubicin

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

Geneesmiddel: Vincristine

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

Geneesmiddel: Prednisolone

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

Geneesmiddel: Lenalidomide

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

Andere namen:
  • Revlimid
Geneesmiddel: Pegfilgrastim

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

Andere namen:
  • Pegfilgastim
Experimenteel: Arm B -

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.
Geneesmiddel: Rituximab

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

Geneesmiddel: Cyclophosphamide

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

Geneesmiddel: Doxorubicin

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

Geneesmiddel: Vincristine

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

Geneesmiddel: Prednisolone

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

Geneesmiddel: Lenalidomide

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

Andere namen:
  • Revlimid
Geneesmiddel: Pegfilgrastim

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

Andere namen:
  • Pegfilgastim
Geneesmiddel: 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.

Andere namen:
  • Cardioxaan

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
The incidence of AICD.
Tijdsspanne: 12 months after LPI

The incidence of AICD (measured with 2D) within 12 months after registration is reported in the eCRF.
12 months after LPI

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Complete Metabolic Remission.
Tijdsspanne: 12 months after LPI

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.
12 months after LPI
Overall survival (OS).
Tijdsspanne: 12 months after LPI

Overall survival (OS) at 12-months is reported in the eCRF.
12 months after LPI
Progression-free survival.
Tijdsspanne: 12 months after LPI

Progression-free survival (PFS) at 12-months is reported in the eCRF.
12 months after LPI
LVEF and global longitudinal strain (GLS).
Tijdsspanne: 12 months after LPI

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.
12 months after LPI
NYHA.
Tijdsspanne: 12 months after LPI

NYHA functional class is reported in the eCRF.
12 months after LPI
Cardiac biomarkers.
Tijdsspanne: 12 months after LPI

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). Items are reported in the eCRF.
12 months after LPI
Quality of Life.
Tijdsspanne: 12 months after LPI

To analyse the impact of the addition of dexrazoxane on QoL via validated questionaires such as QLQ-C30, NHL-HG29, PRO-CTCAE. Data are collected.
12 months after LPI

Andere uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Safety and toxicity.
Tijdsspanne: 12 months after LPI

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
12 months after LPI
Secondary malignancies.
Tijdsspanne: 12 months after LPI

Incidence of secondary malignancies.
12 months after LPI
Major Adverse Cardiovascular Events.
Tijdsspanne: 1- 2-, 5- and 10 years

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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Stichting Hemato-Oncologie voor Volwassenen Nederland

Medewerkers

UMC Utrecht
Amsterdam UMC, location VUmc
The Dutch Network for Cardiovascular Research (WCN)

Onderzoekers

  • Hoofdonderzoeker: A. van Rhenen, MD, UMC Utrecht
  • Hoofdonderzoeker: M.P.M. Linschoten, MD, Amsterdam UMC

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Nuttige links

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

15 augustus 2024

Primaire voltooiing (Geschat)

15 december 2028

Studie voltooiing (Geschat)

15 december 2028

Studieregistratiedata

Eerst ingediend

11 januari 2024

Eerst ingediend dat voldeed aan de QC-criteria

22 januari 2024

Eerst geplaatst (Werkelijk)

23 januari 2024

Updates van studierecords

Laatste update geplaatst (Werkelijk)

23 september 2026

Laatste update ingediend die voldeed aan QC-criteria

18 september 2026

Laatst geverifieerd

1 oktober 2025

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • HO170 DLBCL-ANTICIPATE
  • 2023-505377-32 (Andere identificatie: EU CT number)
  • 2023 (Subsidie/contract van de Amerikaanse NIH)

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

JA

Beschrijving IPD-plan

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.

IPD-tijdsbestek voor delen

After the publication of primary endpoint analysis.

IPD delen Ondersteunend informatietype

  • LEERPROTOCOOL
  • SAP

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

product vervaardigd in en geëxporteerd uit de V.S.

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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