Diffuse Large B-cell LymphomaPhase 2NCT06290817
Orelabrutinib Combined With R-CDOP for DLBCL Patients With High-risk of CNS Relapse Defined by CNS-IPI
A Phase 2 study testing Orelabrutinib combined with R-CDOP regimen in people with Diffuse Large B-cell Lymphoma, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 6 sites in China.
Trial summary
This is a prospective, multicenter, single-arm clinical study on the treatment of newly diagnosed diffuse large B-cell lymphoma with high-risk of CNS relapse defined by CNS-IPI using Orelabrutinib in combination with R-CDOP regimen. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B-cell Lymphoma
- What is being tested?
- Orelabrutinib combined with R-CDOP regimen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 6 sitesChina
- Study dates
- 30 Mar 2023to 20 Mar 2026
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years old; ECOG score 0-3;
- Histologically confirmed diffuse large B-cell lymphoma, including DLBCL and transformed DLBCL;
- CNS-IPI≥4 points
- Previously untreated participants with CD20-positive DLBCL,;
- Heart, liver, and kidney function: creatinine < 2 times the normal upper limit (ULN); ALT (alanine aminotransferase)/AST (Aspartate Aminotransferase) < 2.5ULN; Total bilirubin < 2ULN; Cardiac ejection fraction (EF) ≥50%.
- At least one measurable lesion.
- Have the sufficient understanding ability and voluntarily sign informed consent.
Who cannot join
- Patients with evidence of CNS involvement ;
- Clinically significant active cardiovascular disease, such as uncontrolled arrhythmia, uncontrolled hypertension, congestive heart failure, any grade 3 or 4 heart disease as determined by the New York Heart Association (NYHA) functional scale, or a history of myocardial infarction within 6 months before screening;
- Human immunodeficiency virus (HIV) infection;
- Pregnant or lactating women;
- Other tumors that require treatment;
- Uncontrolled active infection;
- The HBV DNA copy number of active hepatitis after antiviral treatment can not be controlled within 2×103/ml.
- unable to understand and follow the research protocol or unable to sign the informed consent.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
China6 sites, 6 recruiting
- Recruiting
Huzhou Central Hospital
Huzhou
Lihong Shou, 13362216921, SLH077@126.COM
- Recruiting
Affiliated hospital of Jiaxing University , the First Hospital of Jiaxing
Jiaxing
Hui Zeng, 13957330440, zhwuhqn@163.com
- Recruiting
Affiliated hospital of Jiaxing University , the Second Hospital of Jiaxing
Jiaxing
Beili Hu, 0573-82080930, 87718916@qq.com
- Recruiting
Ningbo Medical Center LiHuili Hospital
Ningbo
Jing Le, 13566511755, nblejing@aliyun.com
- Recruiting
Taizhou Hospital of Zhejiang
Taizhou
Yiqun Guo, 13515861286, guoqunyi@163.com
- Recruiting
Second Affiliated Hospital, School of Medicine, Zhejiang University
Zhejiang, Zhejiang
Wenbin Qian
Xibin Xiao
About this study
Official title: A Prospective, Multicenter, Single-arm Clinical Study on the Treatment of Newly Diagnosed Diffuse Large B-cell Lymphoma With High-risk of CNS Relapse Defined by CNS-IPI Using Orelabrutinib in Combination With R-CDOP Regimen
This is a prospective, multicenter, single-arm clinical study on the treatment of newly diagnosed diffuse large B-cell lymphoma with high-risk of CNS relapse defined by CNS-IPI using Orelabrutinib in combination with R-CDOP regimen.
Read the detailed description
Diffuse large B-cell lymphoma (DLBCL) is an aggressive form of B-cell lymphoma, where the dual expression of Myc and BCL-2 genes in non-germinal center B-cell like (non-GCB) lymphomas is associated with a poor prognosis when treated with the standard R-CHOP regimen. Bruton's tyrosine kinase (BTK), a key kinase in the B-cell receptor (BCR) signaling pathway, is an important target for the treatment of B-cell lymphomas. Studies have shown that the first-generation BTK inhibitor Ibrutinib when combined with the R-CHOP regimen for previously untreated patients with dual-expressing, non-GCB lymphomas, can improve event-free survival rates. Orelabrutinib, as a new generation BTK inhibitor independently developed in China, possesses higher inhibitory activity against BTK kinase and can penetrate the blood-brain barrier, offering potential benefits for patients at high risk of central nervous system relapse. The novel anthracycline drug-Liposomal Doxorubicin, which has almost no cardiac toxicity, suggests that the combination of Orelabrutinib with the R-CDOP regimen could improve the adverse prognosis of DLBCL patients at high risk of central relapse. This is a prospective, multicenter, single-arm clinical study on the treatment of newly diagnosed diffuse large B-cell lymphoma with high-risk CNS-IPI using Orelabrutinib in combination with R-CDOP regimen. All participants were treated with the Orelabrutinib combined with R-CDOP regimen. The treatment cycles were set every 21 days for a total of 6-8 cycles. During the study treatment period, researchers conducted a tumor assessment (with a 1-week time window allowed) after the screening period and once again after the 4th, 6th, or 8th cycle of treatment to evaluate the antitumor efficacy of the investigational drug. After all treatment cycles were completed, follow-up visits were conducted every 3 months until the end of the 3-year period. The median duration of follow-up was 24 months.
- Conditions
- Diffuse Large B-cell Lymphoma
- Being tested
- Orelabrutinib combined with R-CDOP regimen
- 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.
Orelabrutinib combined with R-CDOP regimenDrug
All participants were treated with the orelabrutinib combined with R-CHOP regimen (O-RCDOP). The treatment plan involved orelabrutinib tablets at 150mg QD (once daily) from day 1 to day 21, Rituximab at 375mg/m2 on day 1; Cyclophosphamide at 750mg/m2 on day 1; Liposomal Doxorubicin at 30mg/m2 on day 0; Vincristine at 25mg/m2 on day 1 (maximum dose 40mg); and Prednisone at 100mg from day 1 to day 5. The treatment cycles were set every 21 days for a total of 6-8 cycles. Dose adjustments were made for elderly patients for Cyclophosphamide and Liposomal Doxorubicin based on age: 70-80% of the dose for those aged 70-80 years old, and 50-60% of the dose for those older than 80 years.
| Study group | Role | What they receive |
|---|---|---|
| Orelabrutinib combined with R-CDOP regimen | Experimental | Participants will receive 150 mg of oral orelabrutinib once daily with R-CDOP on day 1 of each cycle (21 days) Receives: Drug: Orelabrutinib combined with R-CDOP regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
2-year central nervous system relapse rate
The proportion of patients with central nervous system recurrence within two years from enrollment accounted for all patients treated with drugs.
Measured: up to 2 years
Secondary outcomes (7)
Complete Response Rate
The rate of patients who achieved complete response after treatment.
Measured: At the end of Cycle 3 and Cycle 6（each cycle is 21 days）
Overall Response Rate (ORR)
The rate of patients who achieved CR or PR after treatment.
Measured: At the end of Cycle 3 and Cycle 6（each cycle is 21 days）
2-year Overall survival (OS) rate
2-year overall survival (OS) rate Accessed by the investigator
Measured: Up to 2 years
1-year Overall survival (OS) rate
1-year overall survival (OS) rate Accessed by the investigator
Measured: Up to 1 year
2-year progression-free survival (PFS) rate
Number of non-progression cases/all enrolled cases at 2 years
Measured: 2 years after enrollment of final patient
1-year progression-free survival (PFS) rate
Number of non-progression cases/all enrolled cases at 1 year
Measured: 1 year after enrollment of final patient
Occurrence of hematologic adverse events and non-hematologic adverse events according to CTCAE V4.03
The safety of Orelabrutinib is measured by the occurrence of hematologic adverse events and non-hematologic adverse events according to CTCAE V4.03
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2024
- Study start30 Mar 2023
- Primary completion30 Mar 2025 (estimated)
- Study completion20 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diffuse Large B-cell LymphomaStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital, Zhejiang University, School of MedicineThe 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 62 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Huizhou Municipal Central Hospital, Ningbo Medical Center Lihuili Hospital, Affiliated Hospital of Jiaxing University, The Second Affiliated Hospital of Jiaxing University
- Responsible party
- Sponsor
- Investigators
- Wenbin Qian, Study director, 15.1 Second affiliated hospital， School of Medicine， Zhejiang University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06290817
- Sponsor's protocol ID
- 2023-0724
- Status last verified
- Feb 2024
- First submitted
- 27 Feb 2024
- Last updated
- 4 Mar 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Guo Y, Wang J, Lei H, Bao C, Chen P, Shou L, Guo Q, Hu B, Xie Y, Zhong S, Qian W, Xiao X. Efficacy and safety of orelabrutinib plus R-CDOP as first-line therapy in diffuse large B-cell lymphoma with high-risk CNS-IPI: a prospective, multicenter, single-arm, phase II study. Front Oncol. 2026 Oct 21;16:1976858. doi: 10.3389/fonc.2026.1976858. eCollection 2026.
PubMed 42979656
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Multicenter, Single-arm Clinical Study on the Treatment of Newly Diagnosed Diffuse Large B-cell Lymphoma With High-risk of CNS Relapse Defined by CNS-IPI Using Orelabrutinib in Combination With R-CDOP Regimen
- ClinicalTrials.gov ID
- NCT06290817
- Acronym / sponsor ID
- 2023-0724
- Conditions
- Diffuse Large B-cell Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 62 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Collaborators
- Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Huizhou Municipal Central Hospital, Ningbo Medical Center Lihuili Hospital, Affiliated Hospital of Jiaxing University, The Second Affiliated Hospital of Jiaxing University
- Study start
- 30 Mar 2023 (actual)
- Primary completion
- 30 Mar 2025 (estimated)
- Study completion
- 20 Mar 2026 (estimated)
- First posted
- 4 Mar 2024 (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 is a prospective, multicenter, single-arm clinical study on the treatment of newly diagnosed diffuse large B-cell lymphoma with high-risk of CNS relapse defined by CNS-IPI using Orelabrutinib in combination with R-CDOP regimen.
Detailed description
Diffuse large B-cell lymphoma (DLBCL) is an aggressive form of B-cell lymphoma, where the dual expression of Myc and BCL-2 genes in non-germinal center B-cell like (non-GCB) lymphomas is associated with a poor prognosis when treated with the standard R-CHOP regimen. Bruton's tyrosine kinase (BTK), a key kinase in the B-cell receptor (BCR) signaling pathway, is an important target for the treatment of B-cell lymphomas. Studies have shown that the first-generation BTK inhibitor Ibrutinib when combined with the R-CHOP regimen for previously untreated patients with dual-expressing, non-GCB lymphomas, can improve event-free survival rates. Orelabrutinib, as a new generation BTK inhibitor independently developed in China, possesses higher inhibitory activity against BTK kinase and can penetrate the blood-brain barrier, offering potential benefits for patients at high risk of central nervous system relapse. The novel anthracycline drug-Liposomal Doxorubicin, which has almost no cardiac toxicity, suggests that the combination of Orelabrutinib with the R-CDOP regimen could improve the adverse prognosis of DLBCL patients at high risk of central relapse. This is a prospective, multicenter, single-arm clinical study on the treatment of newly diagnosed diffuse large B-cell lymphoma with high-risk CNS-IPI using Orelabrutinib in combination with R-CDOP regimen. All participants were treated with the Orelabrutinib combined with R-CDOP regimen. The treatment cycles were set every 21 days for a total of 6-8 cycles. During the study treatment period, researchers conducted a tumor assessment (with a 1-week time window allowed) after the screening period and once again after the 4th, 6th, or 8th cycle of treatment to evaluate the antitumor efficacy of the investigational drug. After all treatment cycles were completed, follow-up visits were conducted every 3 months until the end of the 3-year period. The median duration of follow-up was 24 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Orelabrutinib combined with R-CDOP regimen | Experimental | Drug: Orelabrutinib combined with R-CDOP regimenParticipants will receive 150 mg of oral orelabrutinib once daily with R-CDOP on day 1 of each cycle (21 days) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age ≥18 years old; ECOG score 0-3;
- Histologically confirmed diffuse large B-cell lymphoma, including DLBCL and transformed DLBCL;
- CNS-IPI≥4 points
- Previously untreated participants with CD20-positive DLBCL,;
- Heart, liver, and kidney function: creatinine < 2 times the normal upper limit (ULN); ALT (alanine aminotransferase)/AST (Aspartate Aminotransferase) < 2.5ULN; Total bilirubin < 2ULN; Cardiac ejection fraction (EF) ≥50%.
Key exclusion criteria (8 listed)
- Patients with evidence of CNS involvement ;
- Clinically significant active cardiovascular disease, such as uncontrolled arrhythmia, uncontrolled hypertension, congestive heart failure, any grade 3 or 4 heart disease as determined by the New York Heart Association (NYHA) functional scale, or a history of myocardial infarction within 6 months before screening;
- Human immunodeficiency virus (HIV) infection;
- Pregnant or lactating women;
- Other tumors that require treatment;
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 |
|---|---|---|
| Orelabrutinib combined with R-CDOP regimenAll participants were treated with the orelabrutinib combined with R-CHOP regimen (O-RCDOP). The treatment plan involved orelabrutinib tablets at 150mg QD (once daily) from day 1 to day 21, Rituximab at 375mg/m2 on day 1; Cyclophosphamide at 750mg/m2 on day 1; Liposomal Doxorubicin at 30mg/m2 on day 0; Vincristine at 25mg/m2 on day 1 (maximum dose 40mg); and Prednisone at 100mg from day 1 to day 5. The treatment cycles were set every 21 days for a total of 6-8 cycles. Dose adjustments were made for elderly patients for Cyclophosphamide and Liposomal Doxorubicin based on age: 70-80% of the dose for those aged 70-80 years old, and 50-60% of the dose for those older than 80 years. | Drug | Orelabrutinib combined with R-CDOP regimen |
Primary outcome
2-year central nervous system relapse rate
Time frame: up to 2 years
The proportion of patients with central nervous system recurrence within two years from enrollment accounted for all patients treated with drugs.
7 secondary outcomes
Complete Response Rate
Time frame: At the end of Cycle 3 and Cycle 6（each cycle is 21 days）
Overall Response Rate (ORR)
Time frame: At the end of Cycle 3 and Cycle 6（each cycle is 21 days）
2-year Overall survival (OS) rate
Time frame: Up to 2 years
1-year Overall survival (OS) rate
Time frame: Up to 1 year
2-year progression-free survival (PFS) rate
Time frame: 2 years after enrollment of final patient
1-year progression-free survival (PFS) rate
Time frame: 1 year after enrollment of final patient
Occurrence of hematologic adverse events and non-hematologic adverse events according to CTCAE V4.03
Time frame: Up to 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2024.
- Derived from this study: PubMed 42979656Guo Y, Wang J, Lei H, Bao C, Chen P, Shou L, Guo Q, Hu B, Xie Y, Zhong S, Qian W, Xiao X. Efficacy and safety of orelabrutinib plus R-CDOP as first-line therapy in diffuse large B-cell lymphoma with high-risk CNS-IPI: a prospective, multicenter, single-arm, phase II study. Front Oncol. 2026 Oct 21;16:1976858. doi: 10.3389/fonc.2026.1976858. eCollection 2026.
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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.
Wenbin Qian study director
15.1 Second affiliated hospital， School of Medicine， Zhejiang University
6 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 Orelabrutinib combined with R-CDOP regimen in people with Diffuse Large B-cell Lymphoma, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 6 sites in China.
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 8 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: status not confirmed, as of the sponsor's last update on 4 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xibin Xiao (13858015535, xiaoxibinzju@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
2-year central nervous system relapse rate (time frame: up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06290817, which also lists 1 linked publication.
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 4 Mar 2024.