Marginal Zone LymphomasPhase 2NCT07008053
BR Combined With OR in Treatment-naïve Marginal Zone Lymphoma
A Phase 2 study testing BR+OR in people with Marginal Zone Lymphomas, run by Tianjin Medical University Cancer Institute and Hospital at 6 sites in China.
Trial summary
This is a multi-center, prospective study. The main purpose is to evaluate the efficacy and safety of BR (bendamustine and zuberitamab) combined with OR (orelabrutinib and zuberitamab) in treatment-naïve patients with marginal zone lymphoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Marginal Zone Lymphomas
- What is being tested?
- BR+OR
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 6 sitesChina
- Study dates
- Jul 2025to Nov 2028
- 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
- Aged ≥18 years, gender not limited;
- Histopathologically confirmed CD20-positive marginal zone lymphoma including MALT, SMZL, NMZL;
- At least one measurable lesion;
- Ann Arbor stage II includes abdominal or intestinal tumor invasion, stage III and IV have indications for treatment (e.g. B symptoms, decreased blood cells, bleeding, large masses, rapid tumor progression);
- Without systemic treatment, MZL that has progressed, recurred, or is not suitable for local treatment after previous local treatment (local treatments include surgery, radiotherapy, Helicobacter pylori treatment, hepatitis C treatment, and CD20 monoclonal antibody monotherapy);
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
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- Major organ function meets 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 invasion, absolute neutrophil count ≥1.0×10^9/L, platelets ≥50×10^9/L, hemoglobin ≥50g/L; b) Blood biochemistry: Total bilirubin ≤1.5 ULN, AST or ALT ≤2 ULN; serum creatinine ≤1.5 ULN;
- Coagulation function: International normalized ratio (INR) ≤1.5 ULN;
- Expected survival time ≥12 months;
- Voluntarily sign a written informed consent form before the trial screening.
Who cannot join
- Currently or previously diagnosed with other malignant tumors, unless curative 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 uncontrolled or significant cardiovascular disease: a) Within 6 months prior to the first dose of the study drug, there was New York Heart Association (NYHA) Class II or above congestive heart failure, unstable angina, myocardial infarction, or any arrhythmia requiring treatment at screening, with a left ventricular ejection fraction (LVEF)<50%; b) Primary cardiomyopathy (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, or unclassified cardiomyopathy); c) History of clinically significant QTc interval prolongation, or QTc interval >470 ms for females and >450 ms for males during the screening period; d) Subjects with symptomatic or pharmacologically treated coronary artery disease; e) Subjects with uncontrolled hypertension (blood pressure not reaching target despite lifestyle modifications and the use of reasonable, tolerable doses of 3 or more antihypertensive drugs (including diuretics) for over 1 month, or blood pressure only effectively controlled with 4 or more antihypertensive drugs.
- Active bleeding within 2 months prior to screening, or currently taking anticoagulant medications, or the investigator considers there to be a definite bleeding tendency;
- History of deep vein thrombosis or pulmonary embolism within the past six months.
- Major surgery within 6 weeks prior to screening or minor surgery within 2 weeks prior to screening. Major surgery is defined as any surgical procedure that requires general anesthesia, except endoscopic procedures performed for diagnostic purposes, which are not considered major surgery
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- Active infection or uncontrolled HBV (positive for HBsAg and/or HBcAb and positive for HBV DNA titer), HCV Ab positive, HIV/AIDS, or other serious infectious diseases;
- Patients currently have pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-induced pneumonia, or other conditions affecting lung function；
- Pregnant or lactating women and women of childbearing age who are unwilling to take contraceptive measures;
- Need to continuously take drugs with moderate to severe inhibitory or strong inductive effects on cytochrome P450 CYP3A;
- Other conditions that the investigator considers unsuitable for participating in this trial.
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
China6 sites
Hunan Cancer Hospital
Changsha, Hunan
Fujian Cancer Hospital
Fuzhou, Fujian
Shandong Cancer Hospital
Jinan, Shandong
The Affiliated Hospital of Qingdao University
Qingdao, Shandong
The Fourth Hospital of Hebei Medical University
Shijiazhuang, Hebei
Tianjin Medical University Cancer Institute and Hospital
Tianjin
Huilai Zhang, 022-23340123, zhlwgq@126.com
About this study
Official title: BR (Bendamustine and Zuberitamab) Combined With OR (Orelabrutinib and Zuberitamab) in Treatment-naïve Marginal Zone Lymphoma: A Multicenter, Prospective Study
This is a multi-center, prospective study. The main purpose is to evaluate the efficacy and safety of BR (bendamustine and zuberitamab) combined with OR (orelabrutinib and zuberitamab) in treatment-naïve patients with marginal zone lymphoma.
Read the detailed description
Marginal zone lymphoma (MZL) represents the second most prevalent indolent lymphoma subtype, accounting for 5-15% of all non-Hodgkin lymphomas. MZL is categorized into three subtypes based on distinct clinical and pathological features: mucosa-associated lymphoid tissue lymphoma (MALT), nodal marginal zone lymphoma (NMZL), and splenic marginal zone lymphoma (SMZL). Currently, there remains no internationally recognized consensus regarding the optimal first-line treatment for MZL. Exploring more effective, low-toxicity treatment regimens for MZL patients is a scientifically valuable and clinically significant attempt. Orelabrutinib, a novel highly selective BTK inhibitor, 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 clinical study involving previously untreated MZL patients. During the induction therapy phase, patients will receive 90 mg/m2 of bendamustine and 375 mg/m2 zuberitamab from cycles 1 to 3, followed by 150 mg of orelabrutinib and 375 mg/m2 zuberitamab from cycles 4 to 6. At the investigator's discretion, patients who achieved a complete response or partial response could be assigned to maintenance therapy, consisting of 150 mg of orelabrutinib for up to 24 cycles.
- Conditions
- Marginal Zone Lymphomas
- Being tested
- BR+OR
- Keywords
- Lymphoma、Marginal zone lymphoma、Orelabrutinib, Bendamustine, Zuberitamab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BR+ORDrug
Patients who meet the inclusion criteria will enter the treatment period, which consists of an induction phase followed by a maintenance phase. During the induction treatment period, a combined treatment of 3 cycles of the BR regimen and 3 cycles of the OR regimen will be administered, every 28-day cycle for 6 cycles. After the induction treatment, the efficacy assessment will determine whether patients with CR or PR proceed to the maintenance treatment period. Orelabrutinib monotherapy will used as maintenance therapy, every 28-day cycle for up to 24 cycles, or until disease progression/recurrence, unacceptable toxicity, death or consent withdrawal.
| Study group | Role | What they receive |
|---|---|---|
| BR (bendamustine and zuberitamab) + OR (orelabrutinib and zuberitamab) | Experimental | Induction therapy: patients will receive 90 mg/m2 of bendamustine and 375 mg/m2 zuberitamab from cycles 1 to 3, followed by 150 mg of orelabrutinib and 375 mg/m2 zuberitamab from cycles 4 to 6.
Maintenance therapy: at the investigator's discretion, patients who achieved a complete response or partial response could be assigned to maintenance therapy, consisting of 150 mg of orelabrutinib for 24 cycles. Receives: Drug: BR+OR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete response rate
Complete response rate is defined as the proportion of patients with a response of CR.
Measured: From enrollment to the end of induction therapy of cycle 6 (each cycle is 28 days)
Secondary outcomes (6)
Overall response rate (ORR)
The ORR is defined as the proportion of patients with a response of CR or PR.
Measured: At the end of induction therapy (6 cycles; each cycle is 28 days)
Time to response (TTR)
TTR is defined as the time from the start of therapy to the first response.
Measured: From the start of therapy to the first documentation of response, assessed up to 3 years.
Duration of Response (DOR)
DOR is defined as the time from documentation of response to treatment to the first documentation of tumor progression or death due to any cause, whichever comes first.
Measured: From the first demonstration of response until disease progression/death, up to 3 years
Progression-free survival (PFS)
PFS is defined as the time from enrollment 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 the date of enrollment until the date of first documented progression, up to 3 years
Overall survival (OS)
OS is defined as the enrollment 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 the date of enrollment until the date of death, up to 3 years
The occurrence of adverse events (AEs)
AEs will be graded by the investigator according to the NCI-CTCAE Version 5.0.
Measured: From the date of enrollment until the date of death, 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 posted6 Jun 2025
- Study startJul 2025 (estimated)
- Primary completionJul 2027 (estimated)
- Study completionNov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Marginal Zone LymphomasStudies of the same condition, open and under way.
- More trials run by Tianjin Medical University Cancer Institute and HospitalThe 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
- 37 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Huilai Zhang, Study director, Tianjin Medical University Cancer Institute and Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07008053
- Sponsor's protocol ID
- BROAD
- Status last verified
- May 2025
- First submitted
- 18 May 2025
- Last updated
- 6 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BR (Bendamustine and Zuberitamab) Combined With OR (Orelabrutinib and Zuberitamab) in Treatment-naïve Marginal Zone Lymphoma: A Multicenter, Prospective Study
- ClinicalTrials.gov ID
- NCT07008053
- Acronym / sponsor ID
- BROAD
- Conditions
- Marginal Zone Lymphomas
- Keywords
- Lymphoma、Marginal zone lymphoma、Orelabrutinib, Bendamustine, Zuberitamab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 37 participants (estimated)
- Lead sponsor
- Tianjin Medical University Cancer Institute and HospitalUniversity, hospital or other
- Study start
- Jul 2025 (estimated)
- Primary completion
- Jul 2027 (estimated)
- Study completion
- Nov 2028 (estimated)
- First posted
- 6 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.
This is a multi-center, prospective study. The main purpose is to evaluate the efficacy and safety of BR (bendamustine and zuberitamab) combined with OR (orelabrutinib and zuberitamab) in treatment-naïve patients with marginal zone lymphoma.
Detailed description
Marginal zone lymphoma (MZL) represents the second most prevalent indolent lymphoma subtype, accounting for 5-15% of all non-Hodgkin lymphomas. MZL is categorized into three subtypes based on distinct clinical and pathological features: mucosa-associated lymphoid tissue lymphoma (MALT), nodal marginal zone lymphoma (NMZL), and splenic marginal zone lymphoma (SMZL). Currently, there remains no internationally recognized consensus regarding the optimal first-line treatment for MZL. Exploring more effective, low-toxicity treatment regimens for MZL patients is a scientifically valuable and clinically significant attempt. Orelabrutinib, a novel highly selective BTK inhibitor, 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 clinical study involving previously untreated MZL patients. During the induction therapy phase, patients will receive 90 mg/m2 of bendamustine and 375 mg/m2 zuberitamab from cycles 1 to 3, followed by 150 mg of orelabrutinib and 375 mg/m2 zuberitamab from cycles 4 to 6. At the investigator's discretion, patients who achieved a complete response or partial response could be assigned to maintenance therapy, consisting of 150 mg of orelabrutinib for up to 24 cycles.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BR (bendamustine and zuberitamab) + OR (orelabrutinib and zuberitamab) | Experimental | Drug: BR+ORInduction therapy: patients will receive 90 mg/m2 of bendamustine and 375 mg/m2 zuberitamab from cycles 1 to 3, followed by 150 mg of orelabrutinib and 375 mg/m2 zuberitamab from cycles 4 to 6. Maintenance therapy: at the investigator's discretion, patients who achieved a complete response or partial response could be assigned to maintenance therapy, consisting of 150 mg of orelabrutinib for 24 cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Aged ≥18 years, gender not limited;
- Histopathologically confirmed CD20-positive marginal zone lymphoma including MALT, SMZL, NMZL;
- At least one measurable lesion;
- Ann Arbor stage II includes abdominal or intestinal tumor invasion, stage III and IV have indications for treatment (e.g. B symptoms, decreased blood cells, bleeding, large masses, rapid tumor progression);
- Without systemic treatment, MZL that has progressed, recurred, or is not suitable for local treatment after previous local treatment (local treatments include surgery, radiotherapy, Helicobacter pylori treatment, hepatitis C treatment, and CD20 monoclonal antibody monotherapy);
Key exclusion criteria (11 listed)
- Currently or previously diagnosed with other malignant tumors, unless curative 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 uncontrolled or significant cardiovascular disease: a) Within 6 months prior to the first dose of the study drug, there was New York Heart Association (NYHA) Class II or above congestive heart failure, unstable angina, myocardial infarction, or any arrhythmia requiring treatment at screening, with a left ventricular ejection fraction (LVEF)<50%; b) Primary cardiomyopathy (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, or unclassified cardiomyopathy); c) History of clinically significant QTc interval prolongation, or QTc interval >470 ms for females and >450 ms for males during the screening period; d) Subjects with symptomatic or pharmacologically treated coronary artery disease; e) Subjects with uncontrolled hypertension (blood pressure not reaching target despite lifestyle modifications and the use of reasonable, tolerable doses of 3 or more antihypertensive drugs (including diuretics) for over 1 month, or blood pressure only effectively controlled with 4 or more antihypertensive drugs.
- Active bleeding within 2 months prior to screening, or currently taking anticoagulant medications, or the investigator considers there to be a definite 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 |
|---|---|---|
| BR+ORPatients who meet the inclusion criteria will enter the treatment period, which consists of an induction phase followed by a maintenance phase. During the induction treatment period, a combined treatment of 3 cycles of the BR regimen and 3 cycles of the OR regimen will be administered, every 28-day cycle for 6 cycles. After the induction treatment, the efficacy assessment will determine whether patients with CR or PR proceed to the maintenance treatment period. Orelabrutinib monotherapy will used as maintenance therapy, every 28-day cycle for up to 24 cycles, or until disease progression/recurrence, unacceptable toxicity, death or consent withdrawal. | Drug | BR (bendamustine and zuberitamab) + OR (orelabrutinib and zuberitamab) |
Primary outcome
Complete response rate
Time frame: From enrollment to the end of induction therapy of cycle 6 (each cycle is 28 days)
Complete response rate is defined as the proportion of patients with a response of CR.
6 secondary outcomes
Overall response rate (ORR)
Time frame: At the end of induction therapy (6 cycles; each cycle is 28 days)
Time to response (TTR)
Time frame: From the start of therapy to the first documentation of response, assessed up to 3 years.
Duration of Response (DOR)
Time frame: From the first demonstration of response until disease progression/death, up to 3 years
Progression-free survival (PFS)
Time frame: From the date of enrollment until the date of first documented progression, up to 3 years
Overall survival (OS)
Time frame: From the date of enrollment until the date of death, up to 3 years
The occurrence of adverse events (AEs)
Time frame: From the date of enrollment until the date of death, up to 3 years
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 6 Jun 2025.
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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.
Huilai Zhang study director
Tianjin Medical University Cancer Institute and Hospital
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 BR+OR in people with Marginal Zone Lymphomas, run by Tianjin Medical University Cancer Institute and Hospital 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 10 inclusion and 11 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: opening soon, as of the sponsor's last update on 6 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 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?
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 Tianjin Medical University Cancer Institute and Hospital (022-23340123, zhlwgq@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete response rate (time frame: From enrollment to the end of induction therapy of cycle 6 (each cycle is 28 days)). 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 6 Jun 2025.