Diffuse Large B Cell LymphomaPhase 2R-CHOEP-brutNCT03399513
Ibrutinib and Standard Immuno-Chemotherapy in Younger, High-Risk Patients With Diffuse Large B-Cell Lymphoma
A Phase 2 study testing Ibrutinib Oral Capsule [Imbruvica] and R-CHOEP chemotherapy in people with Diffuse Large B Cell Lymphoma, run by University Hospital Muenster at 12 sites in Germany.
Trial summary
This study will investigate if treatment results obtained with R-CHOEP in young high-risk patients with diffuse large B-cell lymphoma can be further improved by the addition of ibrutinib to this regimen. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Diffuse Large B Cell Lymphoma
- What is being tested?
- Ibrutinib Oral Capsule [Imbruvica] and R-CHOEP chemotherapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 12 sitesGermany
- Study dates
- 3 May 2018to 23 Dec 2023
- Phase
- Phase 2
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study.
- Age between 18-60 years
- Risk score 2 or 3 according to age-adjusted International Prognostic Index
- Histology: Primary diagnosis of diffuse large B-cell lymphoma
- Performance status: ECOG (toxicity and response criteria of the eastern cooperative oncology group) 0-3
- Stage: all stages according Ann Arbor
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- Absolute neutrophil count: > 1000 cells/microliter (independent of growth factor support)
- Platelet count ≥ 100.000/mm³ or ≥ 50.000/mm³ if bone marrow involvement independent of transfusion support in either situation.
- Alanine-aminotransferase and Aspartate-aminotransferase: < 3 x Upper limit of normal value
- Total Bilirubin: < 1.5 x Upper limit of normal value
- Serum Creatinine: < 2 x Upper limit of normal value or estimated Glomerular filtration rate (Glomerular filtration rate [Cockcroft-Gault]) ≥ 40 ml/min
- Women of childbearing potential and men who are sexually active must be practising a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during and after the study. For male subjects, these restrictions apply for 6 months after last dose of study drug. For female subjects, they apply for 12 months after last dose of study drug.
- Women of childbearing potential must have negative serum or urine beta-human chorionic gonadotropin pregnancy test at screening. Women who are pregnant or breast-feeding are ineligible for this study.
- Willing/ able to adhere to the prohibitions and restrictions specified in this protocol.
Who cannot join
- Vaccinated with live, attenuated vaccines within 4 weeks of inclusion.
- Major surgery within 4 weeks of inclusion.
- Any prior lymphoma-directed therapy (except pre-phase treatment).
- Known central nervous system involvement.
- Diagnosed or treated for malignancy other than diffuse large B-cell lymphoma, in particular any other (indolent) lymphoma.
- Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional classification.
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- Bone marrow involvement > 25%
- History of stroke or intracranial hemorrhage within six months of inclusion.
- Requires anticoagulation with warfarin or equivalent vitamin K antagonist.
- Known history of human immunodeficiency virus or active hepatitis C virus or active hepatitis B virus infection or any uncontrolled active systemic infection requiring IV antibiotics.
- Requires treatment with strong CYP3A inhibitors.
- Use of preparations containing St. John's Wort.
- Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk.
- Concurrent treatment with other investigational agent or X-ray therapy.
- Previous chemo- or radiotherapy for any other malignancy, in particular indolent lymphoma.
- Any psychological, cognitive, familial, sociological or geographical condition that, in the investigator's opinion, compromises the patient's ability to understand the patient information, to give informed consent or to comply with the study protocol.
- Participation in another interventional clinical trial during this trial. There may be exceptions at the discretion of the coordinating investigator.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
Germany12 sites
HELIOS Hospital Berlin-Buch
Berlin, 13125
Hospital Chemnitz
Chemnitz, 09116
University Hospital Cologne
Cologne, 50937
University Hospital Göttingen
Göttingen, 37075
University Hospital Hamburg-Eppendorf
Hamburg, 20246
University Hospital Heidelberg
Heidelberg, 69120
Saarland University Hospital
Homburg, 66421
Johannes Wesling Hospital Minden
Minden, 32429
University Hospital Muenster
Münster, 48149
Rostock University Medical Center
Rostock, 18057
University Hospital Tuebingen
Tübingen, 72076
University Hospital Ulm
Ulm, 89081
About this study
Official title: Ibrutinib and Standard Immuno-Chemotherapy (R-CHOEP-14) in Younger, High-Risk Patients With Diffuse Large B-Cell Lymphoma
This study will investigate if treatment results obtained with R-CHOEP in young high-risk patients with diffuse large B-cell lymphoma can be further improved by the addition of ibrutinib to this regimen.
Read the detailed description
Encouraging results have been achieved in younger high-risk patients with newly diagnosed diffuse large B-cell lymphoma treated with R-CHOEP. However, more than one fourth of patients still relapse or show primary progressive disease. The outcome of such patients is poor, in particular if first-line therapy contained rituximab. In order to avoid such detrimental situations, we seek to further improve progression-free survival and overall survival by combining R-CHOEP with ibrutinib.
Ibrutinib is a first-in-class, orally administered, potent, small-molecule inhibitor of Bruton's tyrosine kinase, a mediator of critical B-cell signaling pathways implicated in the pathogenesis of B-cell cancers.
- Conditions
- Diffuse Large B Cell Lymphoma
- Being tested
- Ibrutinib Oral Capsule [Imbruvica], R-CHOEP chemotherapy
- Keywords
- Ibrutinib
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ibrutinib Oral Capsule [Imbruvica]Drug
Imbruvica 140 mg hard capsules (Active substance: Ibrutinib)
R-CHOEP chemotherapyDrug
Immunochemotherapy
| Study group | Role | What they receive |
|---|---|---|
| Ibrutinib and R-CHOEP chemotherapy | Experimental | All patients will receive 8 cycles of R-CHOEP immunochemotherapy every two weeks with the following doses per cycle: rituximab 375 mg/m², cyclophosphamide 750 mg/m², doxorubicin 50 mg/m², vincristine 1.4 mg/m² (dose capped at 2 mg), etoposide 300 mg/m², prednisolone 500 mg.
In addition, ibrutinib capsules will be administered orally once daily at a dose of 560 mg (4 x 140 mg hard capsules) for 112 days. Receives: Drug: Ibrutinib Oral Capsule [Imbruvica]; Drug: R-CHOEP chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
2-year progression-free survival
Length of time that a patient lives without disease progression or relapse.
Measured: From the day of inclusion into the study until one of the following events occurs, whichever is first: disease progression, relapse, death due to any other cause (assessed up to 4 years).
Secondary outcomes (14)
Overall survival
The percentage of patients in this study who are still alive.
Measured: From the day of inclusion into the study to death due to any cause (assessed up to 4 years).
Event-free survival
Length of time that a patient remains free of certain events (disease progression, start of additional, unplanned anti-tumor therapy, relapse, death due to any other cause).
Measured: From the day of inclusion into the study until one of the following events occurs, whichever comes first: disease progression, start of additional, unplanned anti-tumor therapy, relapse, death due to any other cause (assessed up to 4 years).
Rate of complete remission
Rate of complete remission measured as number of complete remissions divided by the number of patients included.
Measured: From the day of inclusion into the study until date of complete remission (assessed up to 6 months).
Rate of partial remission
Rate of partial remission measured as number of partial remissions divided by the number of patients included.
Measured: From the day of inclusion into the study until date of partial remission (assessed up to 6 months).
Overall response rate
Overall response rate measured as number of complete and partial remissions divided by the number of patients included.
Measured: From the day of inclusion into the study until date of complete or partial remission (assessed up to 6 months).
Progression rate
Progression rate measured as number of progressions divided by the number of patients included.
Measured: From the day of inclusion into the study until date of progression during therapy or within 2 months after last treatment course (assessed up to 6 months).
Relapse rate
Relapse rate measured as number of relapses divided by the number of patients included.
Measured: From the day of inclusion into the study until date of relapse during therapy or within 2 months after last treatment course (assessed up to 6 months).
Duration of response
The time between the initial response to therapy and subsequent disease progression or relapse.
Measured: From documentation of tumor response to disease progression or relapse (assessed up to 6 months).
Adverse events and serious adverse events
Frequency of adverse events and serious adverse events
Measured: The documentation of adverse events, including serious adverse events, starts with first study treatment after patient inclusion and ends 100 days after the last application of ibrutinib or any component of R-CHOEP (whichever is applied last).
Rate of treatment-related deaths
The number of deaths during therapy or up to 2 months after the end of therapy divided by the number of patients who started study treatment.
Measured: From the start of therapy up to 2 months after the end of therapy.
Therapy cycles (number)
Number of therapy cycles
Measured: From the start of therapy until the end of therapy (assessed up to 4 months).
Therapy cycles (duration)
Duration of therapy cycles
Measured: From the start of therapy until the end of therapy (assessed up to 4 months).
Used drugs
Cumulative doses of R-CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, rituximab) and ibrutinib.
Measured: From the start of therapy until the end of therapy (assessed up to 4 months).
Outcome according to lymphoma biology
Lymphoma tissue from all patients will be characterized.
Measured: From the start of study until the end of study (assessed up to 4 years).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2018
- Study start3 May 2018
- Primary completion23 Dec 2023
- Study completion23 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Large B Cell LymphomaStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Muenster
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen-Cilag G.m.b.H
- Responsible party
- Sponsor
- Investigators
- Prof. Norbert Schmitz, MD, Principal investigator, University Hospital Muenster
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03399513
- Sponsor's protocol ID
- UKM17_0017
- Acronym
- R-CHOEP-brut
- Status last verified
- Jan 2024
- First submitted
- 18 Dec 2017
- Last updated
- 5 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ibrutinib and Standard Immuno-Chemotherapy (R-CHOEP-14) in Younger, High-Risk Patients With Diffuse Large B-Cell Lymphoma
- ClinicalTrials.gov ID
- NCT03399513
- Acronym / sponsor ID
- R-CHOEP-brut / UKM17_0017
- Conditions
- Diffuse Large B Cell Lymphoma
- Keywords
- Ibrutinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University Hospital MuensterUniversity, hospital or other
- Collaborators
- Janssen-Cilag G.m.b.H
- Study start
- 3 May 2018 (actual)
- Primary completion
- 23 Dec 2023 (actual)
- Study completion
- 23 Dec 2023 (actual)
- First posted
- 16 Jan 2018 (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.
This study will investigate if treatment results obtained with R-CHOEP in young high-risk patients with diffuse large B-cell lymphoma can be further improved by the addition of ibrutinib to this regimen.
Detailed description
Encouraging results have been achieved in younger high-risk patients with newly diagnosed diffuse large B-cell lymphoma treated with R-CHOEP. However, more than one fourth of patients still relapse or show primary progressive disease. The outcome of such patients is poor, in particular if first-line therapy contained rituximab. In order to avoid such detrimental situations, we seek to further improve progression-free survival and overall survival by combining R-CHOEP with ibrutinib.
Ibrutinib is a first-in-class, orally administered, potent, small-molecule inhibitor of Bruton's tyrosine kinase, a mediator of critical B-cell signaling pathways implicated in the pathogenesis of B-cell cancers.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ibrutinib and R-CHOEP chemotherapy | Experimental | Drug: Ibrutinib Oral Capsule [Imbruvica], Drug: R-CHOEP chemotherapyAll patients will receive 8 cycles of R-CHOEP immunochemotherapy every two weeks with the following doses per cycle: rituximab 375 mg/m², cyclophosphamide 750 mg/m², doxorubicin 50 mg/m², vincristine 1.4 mg/m² (dose capped at 2 mg), etoposide 300 mg/m², prednisolone 500 mg. In addition, ibrutinib capsules will be administered orally once daily at a dose of 560 mg (4 x 140 mg hard capsules) for 112 days. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study.
- Age between 18-60 years
- Risk score 2 or 3 according to age-adjusted International Prognostic Index
- Histology: Primary diagnosis of diffuse large B-cell lymphoma
- Performance status: ECOG (toxicity and response criteria of the eastern cooperative oncology group) 0-3
Key exclusion criteria (17 listed)
- Vaccinated with live, attenuated vaccines within 4 weeks of inclusion.
- Major surgery within 4 weeks of inclusion.
- Any prior lymphoma-directed therapy (except pre-phase treatment).
- Known central nervous system involvement.
- Diagnosed or treated for malignancy other than diffuse large B-cell lymphoma, in particular any other (indolent) lymphoma.
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 |
|---|---|---|
| Ibrutinib Oral Capsule [Imbruvica]Imbruvica 140 mg hard capsules (Active substance: Ibrutinib) | Drug | Ibrutinib and R-CHOEP chemotherapy |
| R-CHOEP chemotherapyImmunochemotherapy | Drug | Ibrutinib and R-CHOEP chemotherapy |
Primary outcome
2-year progression-free survival
Time frame: From the day of inclusion into the study until one of the following events occurs, whichever is first: disease progression, relapse, death due to any other cause (assessed up to 4 years).
Length of time that a patient lives without disease progression or relapse.
14 secondary outcomes
Overall survival
Time frame: From the day of inclusion into the study to death due to any cause (assessed up to 4 years).
Event-free survival
Time frame: From the day of inclusion into the study until one of the following events occurs, whichever comes first: disease progression, start of additional, unplanned anti-tumor therapy, relapse, death due to any other cause (assessed up to 4 years).
Rate of complete remission
Time frame: From the day of inclusion into the study until date of complete remission (assessed up to 6 months).
Rate of partial remission
Time frame: From the day of inclusion into the study until date of partial remission (assessed up to 6 months).
Overall response rate
Time frame: From the day of inclusion into the study until date of complete or partial remission (assessed up to 6 months).
Progression rate
Time frame: From the day of inclusion into the study until date of progression during therapy or within 2 months after last treatment course (assessed up to 6 months).
Relapse rate
Time frame: From the day of inclusion into the study until date of relapse during therapy or within 2 months after last treatment course (assessed up to 6 months).
Duration of response
Time frame: From documentation of tumor response to disease progression or relapse (assessed up to 6 months).
Adverse events and serious adverse events
Time frame: The documentation of adverse events, including serious adverse events, starts with first study treatment after patient inclusion and ends 100 days after the last application of ibrutinib or any component of R-CHOEP (whichever is applied last).
Rate of treatment-related deaths
Time frame: From the start of therapy up to 2 months after the end of therapy.
Therapy cycles (number)
Time frame: From the start of therapy until the end of therapy (assessed up to 4 months).
Therapy cycles (duration)
Time frame: From the start of therapy until the end of therapy (assessed up to 4 months).
Used drugs
Time frame: From the start of therapy until the end of therapy (assessed up to 4 months).
Outcome according to lymphoma biology
Time frame: From the start of study until the end of study (assessed up to 4 years).
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 5 Jan 2024.
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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.
Prof. Norbert Schmitz, MD principal investigator
University Hospital Muenster
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ibrutinib Oral Capsule [Imbruvica] and R-CHOEP chemotherapy in people with Diffuse Large B Cell Lymphoma, run by University Hospital Muenster at 12 sites in Germany.
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 14 inclusion and 17 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 5 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Germany. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
2-year progression-free survival (time frame: From the day of inclusion into the study until one of the following events occurs, whichever is first: disease progression, relapse, death due to any other cause (assessed up to 4 years).). 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 5 Jan 2024.