Marginal Zone LymphomaPhase 2NCT06504940
Optimize Study - Orelabrutinib Combined With BR/G in Untreated Marginal Zone Lymphoma (MZL)
A Phase 2 study testing Orelabrutinib combined with bendamustine and rituximab and Orelabrutinib combined with obinutuzumab in people with Marginal Zone Lymphoma, run by First Affiliated Hospital of Zhejiang University at 1 site in China.
Trial summary
This is a multi-center, prospective cohort study. The main purpose of Cohort A is to evaluate the efficacy and safety of Orelabrutinib combined with BR (bendamustine and rituximab) for previously untreated young patients with MZL; the purpose of Cohort B is to assess the efficacy and safety of Orelabrutinib combined… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Marginal Zone Lymphoma
- What is being tested?
- Orelabrutinib combined with bendamustine and rituximab and Orelabrutinib combined with obinutuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 69 participants
- Where
- 1 siteChina
- Study dates
- 28 Jun 2024to 8 Jul 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- For Cohort A: Age 18-70 years, physical condition assessed by a physician as suitable for chemotherapy; for Cohort B: Age 70 or older or under 70 years of age assessed by a physician as unsuitable for chemotherapy.
- Gender is not limited.
- Confirmed by histopathology, marginal zone lymphoma including MALT, SMZL, NMZL.
- Progression, recurrence after local treatment, or unsuitable for local treatment (local treatments include surgery, radiotherapy, Helicobacter pylori treatment, hepatitis C treatment).
- ECOG performance score 0-3 points (if the score is 3 points, the physician needs to assess that the deterioration of physical condition is mainly due to tumor burden).
- Indications for treatment (with B symptoms, blood cell decline, bleeding, large mass, rapid progression of tumors, etc.).
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- Major organ functions meet the following criteria: a) Complete blood count: Absolute neutrophil count ≥1.5×10^9/L, platelets ≥75×10^9/L, hemoglobin ≥75g/L; if accompanied by bone marrow involvement, absolute neutrophil count ≥1.0×10^9/L, platelets ≥50×10^9/L, hemoglobin ≥50g/L. b) Blood biochemistry: Total bilirubin ≤1.5 times the upper limit of normal (ULN), AST or ALT ≤2 times ULN; serum creatinine ≤1.5 times ULN; serum amylase ≤ULN. c) Coagulation function: International normalized ratio (INR) ≤1.5 times ULN.
- Life expectancy ≥3 months.
- Voluntarily sign a written informed consent form before the trial screening.
Who cannot join
- Currently or previously have other malignant tumors, unless radical treatment has been performed and there is evidence of no recurrence or metastasis within the last 5 years.
- Lymphoma involving the central nervous system or transformation to a higher grade.
- Have uncontrollable or significant cardiovascular diseases, including: a) Within 6 months before the first administration of the study drug, there is a history of New York Heart Association (NYHA) class II or above congestive heart failure, unstable angina, myocardial infarction, or arrhythmias requiring treatment at the time of screening, with a left ventricular ejection fraction (LVEF) \<50%. b) Primary cardiomyopathy (such as dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, unclassified cardiomyopathy). c) A history of clinically significant QTc interval prolongation, or a QTc interval \>470ms in females and \>450ms in males during the screening period. d) Symptomatic or medication-requiring coronary artery heart disease subjects. e) Subjects with uncontrollable hypertension (despite lifestyle improvements and the use of reasonable, tolerable, and adequate doses of three or more antihypertensive drugs, including diuretics, for more than 1 month, blood pressure is still not at the standard, or it is only effectively controlled when taking four or more antihypertensive drugs).
- Active bleeding within 2 months before screening, or currently taking anticoagulant drugs, or the investigator believes there is a clear bleeding tendency.
- History of deep vein thrombosis or pulmonary embolism within the past six months.
- Clinically significant gastrointestinal abnormalities that may affect the intake, transport, or absorption of drugs (such as inability to swallow, chronic diarrhea, intestinal obstruction), or subjects who have undergone total gastrectomy.
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- History of organ transplantation or allogeneic bone marrow transplantation.
- Major surgery within 6 weeks before screening or minor surgery within 2 weeks before screening. Major surgery is surgery that uses general anesthesia, but endoscopic examinations for diagnostic purposes are not considered major surgery. Insertion of vascular access devices will be exempt from this exclusion criterion.
- Active infection or uncontrolled HBV (positive for HBsAg and/or HBcAb with positive HBV DNA titer), positive for HCV Ab, HIV/AIDS, or other serious infectious diseases; define active infection.
- Subjects currently with pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, etc., that seriously affect lung function.
- Previously treated with BTK, BCR pathway inhibitors (such as PI3K, Syk), and BCL-2 inhibitors.
- Pregnant, breastfeeding women, and subjects of childbearing age who are unwilling to take contraceptive measures.
- Need to continuously take drugs with moderate to severe inhibitory effects on cytochrome P450 CYP3A or strong inductive effects.
- Other situations deemed unsuitable for participating in this trial by the investigator.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Wenjuan Yu contact
China1 site, 1 recruiting
- Recruiting
The First Affiliated Hospital ，Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310003
Xuewu Zhang, +86 15168316013, moyu0718@126.com
About this study
Official title: Orelabrutinib Combined With BR/G Followed by Orelabrutinib Maintenance Therapy for Newly Diagnosed Marginal Zone Lymphoma (MZL): A Prospective ,Multicenter, Clinical Study
This is a multi-center, prospective cohort study. The main purpose of Cohort A is to evaluate the efficacy and safety of Orelabrutinib combined with BR (bendamustine and rituximab) for previously untreated young patients with MZL; the purpose of Cohort B is to assess the efficacy and safety of Orelabrutinib combined with G (Obinutuzumab) followed by Orelabrutinib maintenance therapy for previously untreated elderly patients with MZL.
Read the detailed description
Marginal Zone Lymphoma (MZL) is a group of B-cell malignancies believed to originate from B lymphocytes, typically found in the marginal zones of lymphoid follicles in the spleen, lymph nodes, and mucosa-associated lymphoid tissues. Currently, there is no unified, high-level evidence-based treatment plan for previously untreated MZL. Exploring more effective, low-toxicity treatment plans for MZL patients is a scientifically valuable and clinically significant attempt. With the development of new drugs, new drug regimens have become prominent in the treatment of MZL, and there is an increasing amount of research data on BTK inhibitors in the field of MZL. The BTK inhibitor Orelabrutinib has shown good efficacy in MZL and has been approved by the NMPA for the treatment of MZL in patients who have received at least one prior treatment.
This study is a multi-center, prospective cohort clinical study for previously untreated MZL. Cohort A: For individuals under 70 years of age with good fitness, they will receive three cycles of Orelabrutinib combined with bendamustine and rituximab (BR: bendamustine 70mg/m^2 on days 1-2; rituximab 375mg/m^2 on day 0). Patients achieving PR or better will enter the Orelabrutinib monotherapy maintenance phase (up to 21 cycles, each cycle 28 days). Cohort B: For individuals aged 70 or older or those under 70 years with poor fitness, they will receive six cycles of Orelabrutinib combined with obinutuzumab (G 1000mg iv on days 1, 8, 15 of cycle 1, and day 1 of cycles 2-6; Orelabrutinib 150mg once daily). Patients achieving PR or better will enter the Orelabrutinib monotherapy maintenance phase (up to 18 cycles, each cycle 28 days ).
- Conditions
- Marginal Zone Lymphoma
- Being tested
- Orelabrutinib combined with bendamustine and rituximab, Orelabrutinib combined with obinutuzumab
- Keywords
- orebrutinib, BTKi, Marginal Zone Lymphoma
- Medical subject headings
- Lymphoma, B-Cell, Marginal Zone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Orelabrutinib combined with bendamustine and rituximabDrug
they will receive three cycles of Orelabrutinib combined with bendamustine and rituximab (BR: bendamustine 70mg/m^2 on days 1-2; rituximab 375mg/m^2 on day 0). Patients achieving PR or better will enter the Orelabrutinib monotherapy maintenance phase (up to 21 cycles, each cycle 28 days).
Orelabrutinib combined with obinutuzumabDrug
they will receive six cycles of Orelabrutinib combined with obinutuzumab (G 1000mg iv on days 1, 8, 15 of cycle 1, and day 1 of cycles 2-6; Orelabrutinib 150mg once daily). Patients achieving PR or better will enter the Orelabrutinib monotherapy maintenance phase (up to 18 cycles, each cycle 28 days ).
| Study group | Role | What they receive |
|---|---|---|
| Cohort A | Experimental | For individuals under 70 years of age with good fitness, Receives: Drug: Orelabrutinib combined with bendamustine and rituximab |
| Cohort B | Experimental | For individuals aged 70 or older or those under 70 years with poor fitness Receives: Drug: Orelabrutinib combined with obinutuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cohort A:the complete response rate (CRR)
CRR is defined as the proportion of patients with a response of CR
Measured: At 3 months.
Cohort B: CRR
CRR is defined as the proportion of patients with a response of CR
Measured: at 6 months
Secondary outcomes (7)
Overall response rate (ORR)
The ORR is defined as the proportion of patients with a response of CR or PR
Measured: Up to 2 years
The 2-year overall survival (OS) rate
Overall survival is defined as the period from the induction registration to death from any cause. Patients who have not died until the time of the analysis will be censored at their last contact date.
Measured: From date of signing the informed consent until the date of death from any cause, whichever came first, assessed up to 2 years
The 2-year progression-free survival (PFS) rate.
Progression free survival (PFS) is defined as the time from registration to the first occurrence of progression or relapse as assessed by the investigator, or death from any cause. PFS for patients without disease progression, relapse, or death will be censored at the time of the last tumor assessment.
Measured: From date of signing the informed consent until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Duration of response
Duration of response as defined as the period from the first response (at least PR) to treatment until evidence of disease progression, relapse or death of any cause. Patients alive without progression and relapse will be censored at the latest tumor assessment date or the stopping date.
Measured: Up to 2 years
TTR
TTR is defined as the time from registration to the first response.
Measured: Up to 2 years
The frequency of grade 3-5 AEs
Adverse events will be graded by the investigator according to the NCI-CTCAE Version 5.0.
Measured: From the first drug administration to one month after the end of treatment.
The occurrence of adverse events and serious adverse events
- Adverse events will be graded by the investigator according to the NCI-CTCAE Version 5.0.
Measured: From the first drug administration to one month after the end of treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2024
- Study start28 Jun 2024
- Primary completion8 Jul 2027 (estimated)
- Study completion8 Jul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Marginal Zone 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 69 participants (estimated)
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital of Zhejiang University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06504940
- Sponsor's protocol ID
- IIT20240202
- Status last verified
- Jul 2025
- First submitted
- 11 Jul 2024
- Last updated
- 27 Feb 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Orelabrutinib Combined With BR/G Followed by Orelabrutinib Maintenance Therapy for Newly Diagnosed Marginal Zone Lymphoma (MZL): A Prospective ,Multicenter, Clinical Study
- ClinicalTrials.gov ID
- NCT06504940
- Acronym / sponsor ID
- IIT20240202
- Conditions
- Marginal Zone Lymphoma
- Keywords
- orebrutinib, BTKi, Marginal Zone Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 69 participants (estimated)
- Lead sponsor
- First Affiliated Hospital of Zhejiang UniversityUniversity, hospital or other
- Study start
- 28 Jun 2024 (actual)
- Primary completion
- 8 Jul 2027 (estimated)
- Study completion
- 8 Jul 2029 (estimated)
- First posted
- 17 Jul 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 multi-center, prospective cohort study. The main purpose of Cohort A is to evaluate the efficacy and safety of Orelabrutinib combined with BR (bendamustine and rituximab) for previously untreated young patients with MZL; the purpose of Cohort B is to assess the efficacy and safety of Orelabrutinib combined with G (Obinutuzumab) followed by Orelabrutinib maintenance therapy for previously untreated elderly patients with MZL.
Detailed description
Marginal Zone Lymphoma (MZL) is a group of B-cell malignancies believed to originate from B lymphocytes, typically found in the marginal zones of lymphoid follicles in the spleen, lymph nodes, and mucosa-associated lymphoid tissues. Currently, there is no unified, high-level evidence-based treatment plan for previously untreated MZL. Exploring more effective, low-toxicity treatment plans for MZL patients is a scientifically valuable and clinically significant attempt. With the development of new drugs, new drug regimens have become prominent in the treatment of MZL, and there is an increasing amount of research data on BTK inhibitors in the field of MZL. The BTK inhibitor Orelabrutinib has shown good efficacy in MZL and has been approved by the NMPA for the treatment of MZL in patients who have received at least one prior treatment.
This study is a multi-center, prospective cohort clinical study for previously untreated MZL. Cohort A: For individuals under 70 years of age with good fitness, they will receive three cycles of Orelabrutinib combined with bendamustine and rituximab (BR: bendamustine 70mg/m^2 on days 1-2; rituximab 375mg/m^2 on day 0). Patients achieving PR or better will enter the Orelabrutinib monotherapy maintenance phase (up to 21 cycles, each cycle 28 days). Cohort B: For individuals aged 70 or older or those under 70 years with poor fitness, they will receive six cycles of Orelabrutinib combined with obinutuzumab (G 1000mg iv on days 1, 8, 15 of cycle 1, and day 1 of cycles 2-6; Orelabrutinib 150mg once daily). Patients achieving PR or better will enter the Orelabrutinib monotherapy maintenance phase (up to 18 cycles, each cycle 28 days ).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A | Experimental | Drug: Orelabrutinib combined with bendamustine and rituximabFor individuals under 70 years of age with good fitness, |
| Cohort B | Experimental | Drug: Orelabrutinib combined with obinutuzumabFor individuals aged 70 or older or those under 70 years with poor fitness |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- For Cohort A: Age 18-70 years, physical condition assessed by a physician as suitable for chemotherapy; for Cohort B: Age 70 or older or under 70 years of age assessed by a physician as unsuitable for chemotherapy.
- Gender is not limited.
- Confirmed by histopathology, marginal zone lymphoma including MALT, SMZL, NMZL.
- Progression, recurrence after local treatment, or unsuitable for local treatment (local treatments include surgery, radiotherapy, Helicobacter pylori treatment, hepatitis C treatment).
- ECOG performance score 0-3 points (if the score is 3 points, the physician needs to assess that the deterioration of physical condition is mainly due to tumor burden).
Key exclusion criteria (14 listed)
- Currently or previously have other malignant tumors, unless radical treatment has been performed and there is evidence of no recurrence or metastasis within the last 5 years.
- Lymphoma involving the central nervous system or transformation to a higher grade.
- Have uncontrollable or significant cardiovascular diseases, including: a) Within 6 months before the first administration of the study drug, there is a history of New York Heart Association (NYHA) class II or above congestive heart failure, unstable angina, myocardial infarction, or arrhythmias requiring treatment at the time of screening, with a left ventricular ejection fraction (LVEF) \<50%. b) Primary cardiomyopathy (such as dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, unclassified cardiomyopathy). c) A history of clinically significant QTc interval prolongation, or a QTc interval \>470ms in females and \>450ms in males during the screening period. d) Symptomatic or medication-requiring coronary artery heart disease subjects. e) Subjects with uncontrollable hypertension (despite lifestyle improvements and the use of reasonable, tolerable, and adequate doses of three or more antihypertensive drugs, including diuretics, for more than 1 month, blood pressure is still not at the standard, or it is only effectively controlled when taking four or more antihypertensive drugs).
- Active bleeding within 2 months before screening, or currently taking anticoagulant drugs, or the investigator believes there is a clear bleeding tendency.
- History of deep vein thrombosis or pulmonary embolism within the past six months.
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 bendamustine and rituximabthey will receive three cycles of Orelabrutinib combined with bendamustine and rituximab (BR: bendamustine 70mg/m^2 on days 1-2; rituximab 375mg/m^2 on day 0). Patients achieving PR or better will enter the Orelabrutinib monotherapy maintenance phase (up to 21 cycles, each cycle 28 days). | Drug | Cohort A |
| Orelabrutinib combined with obinutuzumabthey will receive six cycles of Orelabrutinib combined with obinutuzumab (G 1000mg iv on days 1, 8, 15 of cycle 1, and day 1 of cycles 2-6; Orelabrutinib 150mg once daily). Patients achieving PR or better will enter the Orelabrutinib monotherapy maintenance phase (up to 18 cycles, each cycle 28 days ). | Drug | Cohort B |
Primary outcome
Cohort A:the complete response rate (CRR)
Time frame: At 3 months.
CRR is defined as the proportion of patients with a response of CR
Cohort B: CRR
Time frame: at 6 months
CRR is defined as the proportion of patients with a response of CR
7 secondary outcomes
Overall response rate (ORR)
Time frame: Up to 2 years
The 2-year overall survival (OS) rate
Time frame: From date of signing the informed consent until the date of death from any cause, whichever came first, assessed up to 2 years
The 2-year progression-free survival (PFS) rate.
Time frame: From date of signing the informed consent until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Duration of response
Time frame: Up to 2 years
TTR
Time frame: Up to 2 years
The frequency of grade 3-5 AEs
Time frame: From the first drug administration to one month after the end of treatment.
The occurrence of adverse events and serious adverse events
Time frame: From the first drug administration to one month after the end of treatment.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 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.
Wenjuan Yu contact
1 site 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 bendamustine and rituximab and Orelabrutinib combined with obinutuzumab in people with Marginal Zone Lymphoma, run by First Affiliated Hospital of Zhejiang University at 1 site 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 9 inclusion and 14 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: looking for participants now, as of the sponsor's last update on 27 Feb 2026. 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 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Xuewu Zhang (+86 15168316013, moyu0718@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cohort A:the complete response rate (CRR) (time frame: At 3 months.). The study lists 2 primary outcomes in all. 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 Feb 2026.