- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06220032
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
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: A. van Rhenen, MD
- Phone Number: +31 107041560
- Email: A.vanRhenen@umcutrecht.nl
Study Contact Backup
- Name: M.P.M. Linschoten, MD
- Email: m.p.m.linschoten@amsterdamumc.nl
Study Locations
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Almelo, Netherlands
- NL-Almelo-ZGTALMELO
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Amstelveen, Netherlands
- NL-Amstelveen-AMSTELLAND
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Apeldoorn, Netherlands
- NL-Apeldoorn-GELREAPELDOORN
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Arnhem, Netherlands
- NL-Arnhem-RIJNSTATE
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Breda, Netherlands
- NL-Breda-AMPHIA
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Delft, Netherlands
- NL-Delft-RDGG
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Den Bosch, Netherlands
- NL-Den Bosch-JBZ
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Den Haag, Netherlands
- NL-Den Haag-HAGA
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Dordrecht, Netherlands
- NL-Dordrecht-ASZ
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Eindhoven, Netherlands
- NL-Eindhoven-CATHARINA
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Eindhoven, Netherlands
- NL-Eindhoven-MAXIMAMC
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Goes, Netherlands
- NL-Goes-ADRZ
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Groningen, Netherlands
- NL-Groningen-MARTINI
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Harderwijk, Netherlands
- NL-Harderwijk-STJANSDALHARDERWIJK
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Hilversum, Netherlands
- NL-Hilversum-TERGOOI
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Hoofddorp, Netherlands
- NL-Hoofddorp-SPAARNEGASTHUIS
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Nieuwegein, Netherlands
- NL-Nieuwegein-ANTONIUS
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Nijmegen, Netherlands
- NL-Nijmegen-CWZ
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Rotterdam, Netherlands
- NL-Rotterdam-IKAZIA
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Schiedam, Netherlands
- NL-Schiedam-FRANCISCUSVLIETLAND
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Sneek, Netherlands
- NL-Sneek-ANTONIUSSNEEK
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Utrecht, Netherlands
- NL-Utrecht-UMCUTRECHT
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Venlo, Netherlands
- NL-Venlo-VIECURI
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Zwolle, Netherlands
- NL-Zwolle-ISALA
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
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);
- Age ≥ 18 years;
- WHO performance status ≤ 2, WHO 3 performance status is allowed when considered directly related to the DLBCL;
- Negative pregnancy test at study entry for women of childbearing potential;
- 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;
- 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;
- Patient is able to adhere to the study visit schedule and other protocol requirements;
- Written informed consent.
Exclusion Criteria:
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
- Non-diagnostic/poor transthoracic echocardiography imaging quality at baseline;
- Severe pulmonary dysfunction defined as breathlessness at rest (COPD GOLD III or IV), unless clearly related to DLBCL;
- Severe neurological or psychiatric disease;
- Inadequate hematological function (absolute Neutrophil Count (ANC) <1.0x109/L or platelets <75x109/L), unless clearly related to DLBCL;
- Significant hepatic dysfunction (serum bilirubin or transaminases ≥ 3 times the upper limit of normal) unless related to lymphoma infiltration of the liver;
- 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;
- Significant renal dysfunction (creatinine clearance < 30 ml/min after rehydration) or requiring dialysis;
- Active uncontrolled fungal, bacterial and/or viral infection;
- Patient known to be HIV-positive;
- Breast-feeding female patients;
- Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule;
- Participation in another clinical trial with anti-cancer therapy or a cardiovascular drug.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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. |
Day 1 Cycle 1-6: 375 mg/m2 (iv)
Day 1 Cycle 1-6: 750 mg/m2 (iv)
Day 1 Cycle 1-6: 50 mg/m2 (iv)
Day 1 Cycle 1-6: 1.4 mg/m2 (max 2 mg) (iv)
Day 1-5 Cycle 1-6: 100 mg (oral)
Day 1-14 Cycle 1-6: 15 mg day (oral) Only in case of a double hit lymphoma.
Other Names:
6 mg (1 dose per cycle) in case of neutropenia.
Pegfilgastim is mandatory in patients that receive R2-CHOP21.
Other Names:
|
Experimental: 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. |
Day 1 Cycle 1-6: 375 mg/m2 (iv)
Day 1 Cycle 1-6: 750 mg/m2 (iv)
Day 1 Cycle 1-6: 50 mg/m2 (iv)
Day 1 Cycle 1-6: 1.4 mg/m2 (max 2 mg) (iv)
Day 1-5 Cycle 1-6: 100 mg (oral)
Day 1-14 Cycle 1-6: 15 mg day (oral) Only in case of a double hit lymphoma.
Other Names:
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.
Other Names:
6 mg (1 dose per cycle) in case of neutropenia.
Pegfilgastim is mandatory in patients that receive R2-CHOP21.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The incidence of AICD.
Time Frame: 12 months after LPI
|
The incidence of AICD (measured with 2D) within 12 months after registration.
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12 months after LPI
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Complete Metabolic Remission.
Time Frame: 12 months after LPI
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Complete metabolic remission (CMR) on 18F-FDG PET-CT at end of treatment 6-8 weeks after completion of 6x R-CHOP21.
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12 months after LPI
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Overall survival (OS).
Time Frame: 12 months after LPI
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Overall survival (OS) at 12-months.
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12 months after LPI
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Progression-free survival.
Time Frame: 12 months after LPI
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Progression-free survival (PFS) at 12-months.
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12 months after LPI
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LVEF and global longitudinal strain (GLS).
Time Frame: 12 months after LPI
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LVEF (2D and 3D) and global longitudinal strain (GLS) at end of treatment and 12-months after start of treatment.
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12 months after LPI
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NYHA.
Time Frame: 12 months after LPI
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NYHA functional class.
|
12 months after LPI
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Cardiac biomarkers.
Time Frame: 12 months after LPI
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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).
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12 months after LPI
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Quality of Life.
Time Frame: 12 months after LPI
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To analyse the impact of the addition of dexrazoxane on QoL via validated questionaires such as QLQ-C30, NHL-HG29, PRO-CTCAE.
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12 months after LPI
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety and toxicity.
Time Frame: 12 months after LPI
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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
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12 months after LPI
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Secondary malignancies.
Time Frame: 12 months after LPI
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Incidence of secondary malignancies.
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12 months after LPI
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Major Adverse Cardiovascular Events.
Time Frame: 1- 2-, 5- and 10 years
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Major Adverse Cardiovascular Events (MACE) at 1-, 2-, 5- and 10-years.
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1- 2-, 5- and 10 years
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: A. van Rhenen, MD, UMC Utrecht
- Principal Investigator: M.P.M. Linschoten, MD, Amsterdam UMC
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Lymphoma
- Lymphoma, B-Cell
- Lymphoma, Large B-Cell, Diffuse
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Protective Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Cardiotonic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Antibiotics, Antineoplastic
- Prednisolone
- Cyclophosphamide
- Lenalidomide
- Rituximab
- Doxorubicin
- Vincristine
- Dexrazoxane
- Razoxane
Other Study ID Numbers
- HO170 DLBCL-ANTICIPATE
- 2023-505377-32 (Other Identifier: EU CT number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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