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Updated June 2026 · ClinicalTrials.gov

RECRUITINGPhase 2INTERVENTIONAL

Optimize Study - Orelabrutinib Combined With BR/G in Untreated Marginal Zone Lymphoma (MZL)

Orelabrutinib Combined With BR/G Followed by Orelabrutinib Maintenance Therapy for Newly Diagnosed Marginal Zone Lymphoma (MZL): A Prospective ,Multicenter, Clinical Study

Optimize Study - Orelabrutinib Combined With BR/G in Untreated Marginal Zone Lymphoma (MZL) (NCT06504940) is a Phase 2 interventional studying Marginal Zone Lymphoma, sponsored by First Affiliated Hospital of Zhejiang University. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against Marginal Zone Lymphoma and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 69 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Marginal Zone Lymphoma subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: 1. 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. 2. Gender is not limited. 3. Confirmed by histopathology, marginal zone lymphoma including MALT, SMZL, NMZL. 4. Progression, recurrence after local treatment, or unsuitable for local treatment (local treatments include surgery, radiotherapy, Helicobacter pylori treatment, hepatitis C treatment). 5. 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). 6. Indications for treatment (with B symptoms, blood cell decline, bleeding, large mass, rapid progression of tumors, etc.). 7. Major organ functions meet the following criteria: a) Complete blood count: Absolute neutrophil count ≥1.5×10\^9/L, platelet count at least 75×10\^9/L, blood count (hemoglobin) at least 75g/L; if accompanied by bone marrow involvement, absolute neutrophil count ≥1.0×10\^9/L, platelet count at least 50×10\^9/L, blood count (hemoglobin) at least 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. 8. Life expectancy ≥3 months. 9. Voluntarily sign a written willing to sign a consent form form before the trial screening. Who Should NOT Join This Trial: 1. 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. 2. Lymphoma involving the central nervous system or transformation to a higher grade. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: 1. 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. 2. Gender is not limited. 3. Confirmed by histopathology, marginal zone lymphoma including MALT, SMZL, NMZL. 4. Progression, recurrence after local treatment, or unsuitable for local treatment (local treatments include surgery, radiotherapy, Helicobacter pylori treatment, hepatitis C treatment). 5. 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). 6. Indications for treatment (with B symptoms, blood cell decline, bleeding, large mass, rapid progression of tumors, etc.). 7. 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. 8. Life expectancy ≥3 months. 9. Voluntarily sign a written informed consent form before the trial screening. Exclusion Criteria: 1. 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. 2. Lymphoma involving the central nervous system or transformation to a higher grade. 3. 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). 4. Active bleeding within 2 months before screening, or currently taking anticoagulant drugs, or the investigator believes there is a clear bleeding tendency. 5. History of deep vein thrombosis or pulmonary embolism within the past six months. 6. 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. 7. History of organ transplantation or allogeneic bone marrow transplantation. 8. 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. 9. 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. 10. Subjects currently with pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, etc., that seriously affect lung function. 11. Previously treated with BTK, BCR pathway inhibitors (such as PI3K, Syk), and BCL-2 inhibitors. 12. Pregnant, breastfeeding women, and subjects of childbearing age who are unwilling to take contraceptive measures. 13. Need to continuously take drugs with moderate to severe inhibitory effects on cytochrome P450 CYP3A or strong inductive effects. 14. Other situations deemed unsuitable for participating in this trial by the investigator.

Treatments Being Tested

DRUG

Orelabrutinib combined with bendamustine and rituximab

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).

DRUG

Orelabrutinib combined with obinutuzumab

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 ).

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

The First Affiliated Hospital ,Zhejiang University School of Medicine
Hangzhou, Zhejiang, China

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06504940), the sponsor (First Affiliated Hospital of Zhejiang University), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT06504940 clinical trial studying?

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. The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT06504940?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT06504940?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT06504940. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06504940. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-06-26 · Data from ClinicalTrials.gov.