Non Hodgkin LymphomaCLARITYNCT07041827
Cardiotoxicity and Other Late Effects After Radiotherapy and Immuno-chemoTherapy in Non-Hodgkin lYmphoma
An observational study of Non Hodgkin Lymphoma and DLBCL, run by The Netherlands Cancer Institute at 1 site in Netherlands.
Trial summary
Survivors of non-Hodgkin lymphoma and a control group will be screened for (sub)clinical cardiovascular disease, to assess the influence of contemporary treatments on risk and burden of (sub)clinical cardiovascular disease and their influence on survival. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Non Hodgkin Lymphoma, DLBCL, Cardiovascular Diseases
- What is being tested?
- Cardiovascular assessment
- How many people
- 217 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Feb 2020to 1 Feb 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: * Survivors: Over the past years, a Dutch multicentre hospital-based patient cohort of 5-year non-Hodgkin lymphoma survivors has been established. Survivors will be invited for the current study by their treating physician through the BETER survivorship clinics, or when patients have been dismissed from clinical follow-up, by their former treating physician (or head of the medical department, if the treating physician is retired) within each BETER clinic. * Siblings: As there are no patients who are unexposed to potential cardiotoxic treatment in the BETER cohort we will request every participating NHL survivor to approach one of their siblings, more specifically the sibling who is closest in birthdate to the birthdate of the survivor, for participation in the study.
Who may be able to join
- 5-15 year survivors from the patient cohort with (mediastinal) large B-cell non-Hodgkin lymphoma (ICD-code 9679) or diffuse large B-cell non-Hodgkin lymphoma (ICD-code 9684), treated with R-CHOP:
- 200 survivors treated between five to ten years ago (2007-2012)
- 150 survivors treated between ten to fifteen years ago (2002-2007)
- Treated in one of the following centers: AVL, Amsterdam UMC (location VUmc or AMC), LUMC, EMC, UMCU, UMCG, UMC Radboud.
- Age at diagnosis 15 up to 60 years.
- Age at the time of inclusion: younger than 75 years old.
- 175 siblings of the above mentioned patients (maximum of 1 sibling per patient) with their date of birth closest to the birthdate of the survivor.
Who cannot join
- Use of immunosuppressant and/or prednisolone
- HIV-infected individuals
- Pregnant women
- Mental disability or psychological condition potentially hampering compliance with the study protocol
- Insufficient understanding of the Dutch language
- Use of immunosuppressant and/or prednisolone
Show all 10Show fewer
- HIV-infected individuals
- Pregnant women
- Mental disability or psychological condition potentially hampering compliance with the study protocol
- Insufficient understanding of the Dutch language
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Netherlands Cancer Institute
Amsterdam, North Holland, 1066CX
About this study
Survivors of non-Hodgkin lymphoma and a control group will be screened for (sub)clinical cardiovascular disease, to assess the influence of contemporary treatments on risk and burden of (sub)clinical cardiovascular disease and their influence on survival.
Read the detailed description
Rationale: Few studies have thus far addressed the burden from treatment-related cardiovascular disease in long-term survivors of non-Hodgkin's lymphoma (NHL). The life expectancy of patients with aggressive B-cell NHL has significantly increased since treatment regimens have improved. Although the addition of rituximab to CHOP chemotherapy does not appear to increase cardiotoxicity during treatment, little is known about the long-term cardiac safety of R-CHOP. Nonetheless, cardiotoxicity due to doxorubicin exposure appears to be a key problem in clinical practice, while radiation exposure of the heart may add to cardiac disease risk.
Objective: The main objective is to assess in detail risk factors for cardiovascular disease and cardiotoxicity and to compare heart function parameters, vascular parameters and biomarkers associated with cardiovascular function among five- tot fifteen-year survivors, treated for aggressive B-cell NHL, and sibling controls and to assess the effects of cumulative doses of individual immuno- and chemotherapeutic agents and radiation of the heart on cardiovascular function parameters. Secondary objectives are to assess the prevalence of other late effects (metabolic syndrome, quality of life and the predictive value of newly developed markers for cardiovascular disease).
Study design: These parameters will be assessed in a cross-sectional study, nested in a well characterized cohort of aggressive B-cell NHL survivors, with a control population consisting of siblings of these survivors.
Study population: 350 survivors will be invited who are between five and fifteen years after treatment with (R-)CHOP with/without mediastinal radiotherapy, and compare them with 175 sibling controls. Eligible participants will be approached and invited to the BETER clinic by their (former) treating physician.
Main study parameters/endpoints: The main study parameters will be echocardiographic systolic and diastolic heart parameters and global longitudinal strain measurement, arterial stiffness (by pulse wave velocity measurements), endothelial function (by peripheral arterial tonometry), electrocardiography, advanced glycation end products (by skin autofluorescence, AGE-reader), presence of (sub)clinical cardiovascular disease and biomarkers. Adverse cardiovascular events, risk factors and quality of life will be assessed through questionnaires and physical measurements. Exposure to (R-)CHOP and radiotherapy will be extracted from the medical history. Multivariable logistic and linear regression analyses will be used for analyses.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: With the results of our study, guidelines for follow up and prevention will be developed which will benefit the participants during their own follow up in the future. The burden of participating is expected to be low since the study is mainly observational and assessments required in the context of research as much as possible combined with the provided standard of care for survivors during one or two hospital visits.
- Conditions
- Non Hodgkin Lymphoma, DLBCL, Cardiovascular Diseases, Cardiomyopathies, Cardiotoxicity, Metabolic Syndrome
- Being tested
- Cardiovascular assessment
- Keywords
- Cardiotoxicity, Non-Hodgkin lymphoma, Late effects, Survivor
- Medical subject headings
- Lymphoma, Non-Hodgkin, Cardiovascular Diseases, Cardiomyopathies, Cardiotoxicity, Metabolic Syndrome, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cardiovascular assessmentDiagnostic test
Also called Blood & urine sampling (biomarkers), Echocardiography, Electrocardiography, Pulse wave velocity (arterial stiffness)
A cardiovascular assessment will be performed to screen for (sub)clinical cardiovascular diseases and to compare the prevalences in survivors of non-Hodgkin lymphoma and a control group.
| Study group | Role | What they receive |
|---|---|---|
| Survivors | Over the past years, a Dutch multicentre hospital-based patient cohort of 5-year non-Hodgkin lymphoma survivors has been established. Survivors will be invited for the current study by their treating physician through the BETER survivorship clinics, or when patients have been dismissed from clinical follow-up, by their former treating physician (or head of the medical department, if the treating physician is retired) within each BETER clinic. Receives: Diagnostic Test: Cardiovascular assessment | |
| Siblings | As there are no patients who are unexposed to potential cardiotoxic treatment in the BETER cohort we will request every participating NHL survivor to approach one of their siblings, more specifically the sibling who is closest in birthdate to the birthdate of the survivor, for participation in the study. Receives: Diagnostic Test: Cardiovascular assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Echocardiography: systolic and diastolic heart parameters, various strain measurements such as global longitudinal strain
LVEF (continuous), LVEF<50%, GLS (continuous) GLS>-18%, NT-proBNP (continuous), NT-proBNP>=125 pg/mL
Measured: Once, at enrollment
Secondary outcomes (7)
Electrocardiography
Presence of cardiac disease
Measured: Once, at enrollment
Pulse wave velocity
Measurement of arterial stiffness / vascular function
Measured: Once, at enrollment
Association of different biomarkers
Value of different biomarkers (Nt-proBNP, Troponin T, sST2, galectin-3, GDF-15, high sensitive CRP)
Measured: Once, at enrollment
EndoPAT (peripheral arterial tonometry)
Measurement of endothelial function / vascular function
Measured: Once, at enrollment
Metabolic syndrome
Defined if 3 out of 5 of the following criteria are present: hypertension, dyslipidemia, diabetes, obesity, increased abdominal circumference
Measured: Once, at enrollment
Questionnaires
Assessment of health related quality of life and symptoms by validated questionnaires: EORTC QLQ-C30, EORTC-NHL-HG29, EORTC-BR29/PR-25 (sexuality items)
Measured: Once, at enrollment
Advanced glycation end products
Assessment of AGEs by skin autofluorescence, as a marker for cardiovascular and metabolic disease
Measured: Once, at enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2025
- Study start1 Feb 2020
- Primary completion1 Oct 2022
- Study completion1 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by The Netherlands Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 217 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Amsterdam UMC, location VUmc
- Responsible party
- Sponsor
- Investigators
- Michael Schaapveld, PhD, Study director, The Netherlands Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07041827
- Sponsor's protocol ID
- M18CNH
- Other IDs
- 10424
- Acronym
- CLARITY
- Status last verified
- Jun 2025
- First submitted
- 20 Feb 2019
- Last updated
- 27 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiotoxicity and Other Late Effects After Radiotherapy and Immuno-chemoTherapy in Non-Hodgkin lYmphoma
- ClinicalTrials.gov ID
- NCT07041827
- Acronym / sponsor ID
- CLARITY / M18CNH
- Conditions
- Non Hodgkin Lymphoma, DLBCL, Cardiovascular Diseases, Cardiomyopathies, Cardiotoxicity, Metabolic Syndrome
- Keywords
- Cardiotoxicity, Non-Hodgkin lymphoma, Late effects, Survivor
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 217 participants (actual)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Collaborators
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Amsterdam UMC, location VUmc
- Study start
- 1 Feb 2020 (actual)
- Primary completion
- 1 Oct 2022 (actual)
- Study completion
- 1 Feb 2023 (actual)
- First posted
- 27 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Survivors of non-Hodgkin lymphoma and a control group will be screened for (sub)clinical cardiovascular disease, to assess the influence of contemporary treatments on risk and burden of (sub)clinical cardiovascular disease and their influence on survival.
Detailed description
Rationale: Few studies have thus far addressed the burden from treatment-related cardiovascular disease in long-term survivors of non-Hodgkin's lymphoma (NHL). The life expectancy of patients with aggressive B-cell NHL has significantly increased since treatment regimens have improved. Although the addition of rituximab to CHOP chemotherapy does not appear to increase cardiotoxicity during treatment, little is known about the long-term cardiac safety of R-CHOP. Nonetheless, cardiotoxicity due to doxorubicin exposure appears to be a key problem in clinical practice, while radiation exposure of the heart may add to cardiac disease risk.
Objective: The main objective is to assess in detail risk factors for cardiovascular disease and cardiotoxicity and to compare heart function parameters, vascular parameters and biomarkers associated with cardiovascular function among five- tot fifteen-year survivors, treated for aggressive B-cell NHL, and sibling controls and to assess the effects of cumulative doses of individual immuno- and chemotherapeutic agents and radiation of the heart on cardiovascular function parameters. Secondary objectives are to assess the prevalence of other late effects (metabolic syndrome, quality of life and the predictive value of newly developed markers for cardiovascular disease).
Study design: These parameters will be assessed in a cross-sectional study, nested in a well characterized cohort of aggressive B-cell NHL survivors, with a control population consisting of siblings of these survivors.
Study population: 350 survivors will be invited who are between five and fifteen years after treatment with (R-)CHOP with/without mediastinal radiotherapy, and compare them with 175 sibling controls. Eligible participants will be approached and invited to the BETER clinic by their (former) treating physician.
Main study parameters/endpoints: The main study parameters will be echocardiographic systolic and diastolic heart parameters and global longitudinal strain measurement, arterial stiffness (by pulse wave velocity measurements), endothelial function (by peripheral arterial tonometry), electrocardiography, advanced glycation end products (by skin autofluorescence, AGE-reader), presence of (sub)clinical cardiovascular disease and biomarkers. Adverse cardiovascular events, risk factors and quality of life will be assessed through questionnaires and physical measurements. Exposure to (R-)CHOP and radiotherapy will be extracted from the medical history. Multivariable logistic and linear regression analyses will be used for analyses.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: With the results of our study, guidelines for follow up and prevention will be developed which will benefit the participants during their own follow up in the future. The burden of participating is expected to be low since the study is mainly observational and assessments required in the context of research as much as possible combined with the provided standard of care for survivors during one or two hospital visits.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Survivors | – | Diagnostic Test: Cardiovascular assessmentOver the past years, a Dutch multicentre hospital-based patient cohort of 5-year non-Hodgkin lymphoma survivors has been established. Survivors will be invited for the current study by their treating physician through the BETER survivorship clinics, or when patients have been dismissed from clinical follow-up, by their former treating physician (or head of the medical department, if the treating physician is retired) within each BETER clinic. |
| Siblings | – | Diagnostic Test: Cardiovascular assessmentAs there are no patients who are unexposed to potential cardiotoxic treatment in the BETER cohort we will request every participating NHL survivor to approach one of their siblings, more specifically the sibling who is closest in birthdate to the birthdate of the survivor, for participation in the study. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- * Survivors: Over the past years, a Dutch multicentre hospital-based patient cohort of 5-year non-Hodgkin lymphoma survivors has been established. Survivors will be invited for the current study by their treating physician through the BETER survivorship clinics, or when patients have been dismissed from clinical follow-up, by their former treating physician (or head of the medical department, if the treating physician is retired) within each BETER clinic. * Siblings: As there are no patients who are unexposed to potential cardiotoxic treatment in the BETER cohort we will request every participating NHL survivor to approach one of their siblings, more specifically the sibling who is closest in birthdate to the birthdate of the survivor, for participation in the study.
Key inclusion criteria (7 listed)
- 5-15 year survivors from the patient cohort with (mediastinal) large B-cell non-Hodgkin lymphoma (ICD-code 9679) or diffuse large B-cell non-Hodgkin lymphoma (ICD-code 9684), treated with R-CHOP:
- Treated in one of the following centers: AVL, Amsterdam UMC (location VUmc or AMC), LUMC, EMC, UMCU, UMCG, UMC Radboud.
- Age at diagnosis 15 up to 60 years.
- Age at the time of inclusion: younger than 75 years old.
- 175 siblings of the above mentioned patients (maximum of 1 sibling per patient) with their date of birth closest to the birthdate of the survivor.
Key exclusion criteria (10 listed)
- Use of immunosuppressant and/or prednisolone
- HIV-infected individuals
- Pregnant women
- Mental disability or psychological condition potentially hampering compliance with the study protocol
- Insufficient understanding of the Dutch language
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cardiovascular assessmentAlso: Blood & urine sampling (biomarkers), Echocardiography, Electrocardiography, Pulse wave velocity (arterial stiffness)A cardiovascular assessment will be performed to screen for (sub)clinical cardiovascular diseases and to compare the prevalences in survivors of non-Hodgkin lymphoma and a control group. | Diagnostic test | Siblings, Survivors |
Primary outcome
Echocardiography: systolic and diastolic heart parameters, various strain measurements such as global longitudinal strain
Time frame: Once, at enrollment
LVEF (continuous), LVEF<50%, GLS (continuous) GLS>-18%, NT-proBNP (continuous), NT-proBNP>=125 pg/mL
7 secondary outcomes
Electrocardiography
Time frame: Once, at enrollment
Pulse wave velocity
Time frame: Once, at enrollment
Association of different biomarkers
Time frame: Once, at enrollment
EndoPAT (peripheral arterial tonometry)
Time frame: Once, at enrollment
Metabolic syndrome
Time frame: Once, at enrollment
Questionnaires
Time frame: Once, at enrollment
Advanced glycation end products
Time frame: Once, at enrollment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Schaapveld, PhD study director
The Netherlands Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Non Hodgkin Lymphoma and DLBCL, run by The Netherlands Cancer Institute at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Echocardiography: systolic and diastolic heart parameters, various strain measurements such as global longitudinal strain (time frame: Once, at enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2025.