Marginal Zone Lymphoma(MZL)Phase 2NCT07917650
PET/CT-Guided Maintenance Therapy in Previously Untreated MZL
A Phase 2 study testing Orelabrutinib in people with Marginal Zone Lymphoma(MZL), run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences at 1 site in China.
Trial summary
A prospective, multicenter, open-label, phase II trial of PET/CT-guided maintenance therapy in newly diagnosed marginal zone lymphoma. After first-line immunochemotherapy, dual-tracer PET/CT (18F-FDG and 68Ga-Pentixafor) is performed. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Marginal Zone Lymphoma(MZL)
- What is being tested?
- Orelabrutinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteChina
- Study dates
- 14 May 2026to 2 Dec 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years ECOG performance status (PS) 0-2 Life expectancy of no less than 12 weeks Marginal zone lymphoma (MZL) confirmed according to the WHO 2022 classification of lymphoid neoplasms, including all three subtypes: splenic MZL, nodal MZL, and extranodal MZL Presence of a treatment indication for MZL per NCCN guidelines, and no prior systemic therapy for MZL (hormonal therapy and anti-infective treatment excepted)
- Adequate organ function, as defined by the following criteria (except when attributable to lymphoma involvement):
- Hematologic function:
- ANC ≥1.0×10⁹/L
- Platelets ≥75×10⁹/L
- Hemoglobin ≥80 g/dL
Show all 10Show fewer
- Biochemical function:
- Total bilirubin (TBIL) <1.5×ULN
- ALT and AST <2.5×ULN (<5×ULN for patients with hepatic involvement)
- Creatinine clearance ≥40 mL/min (Cockcroft-Gault formula) Women of childbearing potential must have practiced reliable contraception or have a negative pregnancy test (serum or urine) within 7 days before enrollment, and must agree to use appropriate contraception during the study and for 8 weeks after the last dose of study drug. Men must agree to use appropriate contraception or have undergone surgical sterilization during the study and for 8 weeks after the last dose of study drug Voluntary participation with signed written informed consent and willingness to comply with follow-up
Who cannot join
- Central nervous system involvement Prior or concurrent malignant tumor that has not been cured, except adequately treated basal cell carcinoma of the skin, carcinoma in situ of the cervix, and superficial bladder cancer Presence of any of the following cardiovascular diseases: myocardial ischemia or myocardial infarction of grade II or above, uncontrolled arrhythmia (including QTc interval ≥450 ms in males and ≥470 ms in females), New York Heart Association (NYHA) class III-IV heart failure, or left ventricular ejection fraction (LVEF) <50% on echocardiography Coagulation abnormalities (INR >1.5, or prothrombin time (PT) >ULN + 4 seconds, or APTT >1.5×ULN), a bleeding tendency, or ongoing thrombolytic or anticoagulant therapy Arterial or venous thromboembolic events within 12 months before enrollment, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, and cerebral infarction), deep vein thrombosis, and pulmonary embolism Known hereditary or acquired bleeding or thrombotic diathesis (e.g., hemophilia, coagulation disorders) Major surgery, severe traumatic injury, fracture, or ulcer within 4 weeks before enrollment Factors that significantly affect the oral absorption of drugs, such as inability to swallow, chronic diarrhea, and intestinal obstruction Active infection requiring antimicrobial therapy (e.g., antibacterial or antiviral agents; excluding anti-HBV therapy for chronic hepatitis B and antifungal therapy) Active hepatitis B (HBV DNA ≥2000 IU/mL or 10⁴ copies/mL) or hepatitis C (positive anti-HCV antibody with HCV RNA above the lower limit of detection of the assay) History of psychotropic substance abuse that cannot be abstained from, or presence of a psychiatric disorder Known allergy to 68Ga-Pentixafor or 18F-FDG Inability to undergo PET/CT examination for other reasons (e.g., claustrophobia, inability to lie supine) Pregnant or lactating women; patients of childbearing potential who are unwilling or unable to use effective contraception Any other condition that, in the judgment of the investigator, may affect the conduct of the clinical study or the assessment of study results.
Trial locations and contacts
1 site in 1 country.
China1 site
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, beijing,
Beijing
About this study
Official title: PET/CT-Guided Maintenance Therapy in Previously Untreated Marginal Zone Lymphoma: A Prospective, Multicenter, Open-Label, Phase II Trial
A prospective, multicenter, open-label, phase II trial of PET/CT-guided maintenance therapy in newly diagnosed marginal zone lymphoma. After first-line immunochemotherapy, dual-tracer PET/CT (18F-FDG and 68Ga-Pentixafor) is performed. Patients with Deauville score 4-5 receive orelabrutinib 150 mg daily for 1 year; those with score 1-3 are observed. Primary endpoint: 2-year progression-free survival rate.
Read the detailed description
Marginal zone lymphoma (MZL) is an indolent B-cell malignancy in which the value of post-induction maintenance therapy remains controversial. This is a prospective, multicenter, open-label, phase II study investigating a PET/CT-guided, response-adapted maintenance strategy in patients with newly diagnosed MZL, including its three subtypes ( extranodal MALT lymphoma, nodal MZL, and splenic MZL). A total of 45 patients will be enrolled (40 evaluable cases, assuming a 10% dropout rate).Patients aged ≥18 years with MZL confirmed per the WHO 2022 lymphoma classification, ECOG performance status 0-2, an indication for systemic treatment per NCCN guidelines, and no prior systemic therapy for MZL (excluding topical and anti-infective treatment) will be eligible. Adequate organ function is required (ANC ≥1.0×10⁹/L, platelets ≥75×10⁹/L, hemoglobin ≥80 g/dL, TBIL <1.5×ULN, ALT/AST <2.5×ULN [<5×ULN with liver involvement], creatinine clearance ≥40 mL/min). Key exclusions include CNS involvement, prior or concurrent uncontrolled malignancy (except cured basal cell carcinoma, cervical carcinoma in situ, and superficial bladder cancer), significant cardiovascular disease, and coagulation abnormalities or thromboembolic events within 12 months.First-line immunochemotherapy (e.g., R-CHOP, R-CVP, or bendamustine-rituximab) will be selected by the treating physician according to routine clinical practice; the study does not intervene in treatment decisions. All patients will undergo dual-tracer PET/CT with 68Ga-Pentixafor and 18F-FDG at two mandatory time points: baseline (before first-line therapy) and end of treatment (after completion of planned first-line therapy). Both scans will be performed within 72 hours of each other at Peking Union Medical College Hospital, with randomized imaging order. Images will be independently and blindly interpreted by two experienced nuclear medicine physicians using the Lugano 2014 criteria; 18F-FDG PET/CT will be graded by the 5-point Deauville scale (score 4-5 defined as PET-positive).At the response-assessment and decision point, post-treatment 18F-FDG PET/CT results will guide the subsequent strategy: patients with a positive scan (Deauville 4-5) will receive maintenance therapy with orelabrutinib 150 mg once daily for 1 year, while patients with a negative scan (Deauville 1-3) will be followed with observation alone. The 68Ga-Pentixafor PET/CT results will be used for exploratory diagnostic-performance comparison only and will not influence treatment decisions.After the decision point, all patients will be followed every 3 months (±7 days) by clinic visit or telephone for at least 2 years, or until death, loss to follow-up, or study completion. The primary endpoint is the 2-year progression-free survival (PFS) rate. Secondary endpoints include the sensitivity, specificity, accuracy, and positive/negative predictive values of both tracers at baseline and end of treatment (with ROC analysis using pathology or clinical follow-up as the reference standard); concordance between 18F-FDG and 68Ga-Pentixafor PET/CT (kappa test); adverse events (CTCAE); and overall survival. PFS and OS will be estimated by the Kaplan-Meier method, and survival will be compared between the PET-positive and PET-negative groups using the log-rank test.
- Conditions
- Marginal Zone Lymphoma(MZL)
- Being tested
- Orelabrutinib
- 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.
OrelabrutinibDrug
After the patient received one cycle of the anti-CD20 monoclonal antibody CVP regimen, obinutuzumab was added starting from the second cycle for combination therapy. After a total of five cycles of the obinutuzumab combined with the anti-CD20 monoclonal antibody CVP regimen, maintenance treatment with obinutuzumab monotherapy was administered for 18 cycles or until disease progression or unacceptable toxicity occurred.
| Study group | Role | What they receive |
|---|---|---|
| Patients with MZL who are treatment-naive | Experimental | Baseline dual-tracer PET/CT with 68Ga-Pentixafor and 18F-FDG will be performed at the Department of Nuclear Medicine, Peking Union Medical College Hospital, before first-line treatment. Patients will then receive standard first-line therapy; upon completion of 6 cycles, both PET/CT scans will be repeated at the same institution. The post-treatment 18F-FDG PET/CT result will determine the subsequent strategy:
PET-positive (Deauville 4-5): maintenance therapy with orelabrutinib 150 mg once daily for 1 year; PET-negative (Deauville 1-3): regular follow-up with observation alone. The 68Ga-Pentixafor PET/CT results will be used for comparative analysis only and will not directly influence treatment decisions. Receives: Drug: Orelabrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
24-month progression-free survival rate
Percentage of patients alive and free from disease progression at 24 months (±4 weeks) after enrollment.
Measured: From enrollment to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2026
- Study start14 May 2026
- Primary completion1 Dec 2029 (estimated)
- Study completion2 Dec 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 Lymphoma(MZL)Studies of the same condition, open and under way.
- More trials run by Cancer Institute and Hospital, Chinese Academy of Medical SciencesThe 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
- Model description
- A multicenter, prospective, interventional study, with a planned number of subjects: approximately 45 cases.
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Xinxin Cao, Study chair, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07917650
- Sponsor's protocol ID
- NCCH-000569
- Status last verified
- Feb 2026
- First submitted
- 30 Oct 2026
- Last updated
- 4 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PET/CT-Guided Maintenance Therapy in Previously Untreated Marginal Zone Lymphoma: A Prospective, Multicenter, Open-Label, Phase II Trial
- ClinicalTrials.gov ID
- NCT07917650
- Acronym / sponsor ID
- NCCH-000569
- Conditions
- Marginal Zone Lymphoma(MZL)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Cancer Institute and Hospital, Chinese Academy of Medical SciencesUniversity, hospital or other
- Study start
- 14 May 2026 (actual)
- Primary completion
- 1 Dec 2029 (estimated)
- Study completion
- 2 Dec 2029 (estimated)
- First posted
- 4 Nov 2026 (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.
A prospective, multicenter, open-label, phase II trial of PET/CT-guided maintenance therapy in newly diagnosed marginal zone lymphoma. After first-line immunochemotherapy, dual-tracer PET/CT (18F-FDG and 68Ga-Pentixafor) is performed. Patients with Deauville score 4-5 receive orelabrutinib 150 mg daily for 1 year; those with score 1-3 are observed. Primary endpoint: 2-year progression-free survival rate.
Detailed description
Marginal zone lymphoma (MZL) is an indolent B-cell malignancy in which the value of post-induction maintenance therapy remains controversial. This is a prospective, multicenter, open-label, phase II study investigating a PET/CT-guided, response-adapted maintenance strategy in patients with newly diagnosed MZL, including its three subtypes ( extranodal MALT lymphoma, nodal MZL, and splenic MZL). A total of 45 patients will be enrolled (40 evaluable cases, assuming a 10% dropout rate).Patients aged ≥18 years with MZL confirmed per the WHO 2022 lymphoma classification, ECOG performance status 0-2, an indication for systemic treatment per NCCN guidelines, and no prior systemic therapy for MZL (excluding topical and anti-infective treatment) will be eligible. Adequate organ function is required (ANC ≥1.0×10⁹/L, platelets ≥75×10⁹/L, hemoglobin ≥80 g/dL, TBIL <1.5×ULN, ALT/AST <2.5×ULN [<5×ULN with liver involvement], creatinine clearance ≥40 mL/min). Key exclusions include CNS involvement, prior or concurrent uncontrolled malignancy (except cured basal cell carcinoma, cervical carcinoma in situ, and superficial bladder cancer), significant cardiovascular disease, and coagulation abnormalities or thromboembolic events within 12 months.First-line immunochemotherapy (e.g., R-CHOP, R-CVP, or bendamustine-rituximab) will be selected by the treating physician according to routine clinical practice; the study does not intervene in treatment decisions. All patients will undergo dual-tracer PET/CT with 68Ga-Pentixafor and 18F-FDG at two mandatory time points: baseline (before first-line therapy) and end of treatment (after completion of planned first-line therapy). Both scans will be performed within 72 hours of each other at Peking Union Medical College Hospital, with randomized imaging order. Images will be independently and blindly interpreted by two experienced nuclear medicine physicians using the Lugano 2014 criteria; 18F-FDG PET/CT will be graded by the 5-point Deauville scale (score 4-5 defined as PET-positive).At the response-assessment and decision point, post-treatment 18F-FDG PET/CT results will guide the subsequent strategy: patients with a positive scan (Deauville 4-5) will receive maintenance therapy with orelabrutinib 150 mg once daily for 1 year, while patients with a negative scan (Deauville 1-3) will be followed with observation alone. The 68Ga-Pentixafor PET/CT results will be used for exploratory diagnostic-performance comparison only and will not influence treatment decisions.After the decision point, all patients will be followed every 3 months (±7 days) by clinic visit or telephone for at least 2 years, or until death, loss to follow-up, or study completion. The primary endpoint is the 2-year progression-free survival (PFS) rate. Secondary endpoints include the sensitivity, specificity, accuracy, and positive/negative predictive values of both tracers at baseline and end of treatment (with ROC analysis using pathology or clinical follow-up as the reference standard); concordance between 18F-FDG and 68Ga-Pentixafor PET/CT (kappa test); adverse events (CTCAE); and overall survival. PFS and OS will be estimated by the Kaplan-Meier method, and survival will be compared between the PET-positive and PET-negative groups using the log-rank test.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- A multicenter, prospective, interventional study, with a planned number of subjects: approximately 45 cases.
| Arm | Type | Receives |
|---|---|---|
| Patients with MZL who are treatment-naive | Experimental | Drug: OrelabrutinibBaseline dual-tracer PET/CT with 68Ga-Pentixafor and 18F-FDG will be performed at the Department of Nuclear Medicine, Peking Union Medical College Hospital, before first-line treatment. Patients will then receive standard first-line therapy; upon completion of 6 cycles, both PET/CT scans will be repeated at the same institution. The post-treatment 18F-FDG PET/CT result will determine the subsequent strategy: PET-positive (Deauville 4-5): maintenance therapy with orelabrutinib 150 mg once daily for 1 year; PET-negative (Deauville 1-3): regular follow-up with observation alone. The 68Ga-Pentixafor PET/CT results will be used for comparative analysis only and will not directly influence treatment decisions. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age ≥18 years ECOG performance status (PS) 0-2 Life expectancy of no less than 12 weeks Marginal zone lymphoma (MZL) confirmed according to the WHO 2022 classification of lymphoid neoplasms, including all three subtypes: splenic MZL, nodal MZL, and extranodal MZL Presence of a treatment indication for MZL per NCCN guidelines, and no prior systemic therapy for MZL (hormonal therapy and anti-infective treatment excepted)
- Adequate organ function, as defined by the following criteria (except when attributable to lymphoma involvement):
- ANC ≥1.0×10⁹/L
- Platelets ≥75×10⁹/L
- Hemoglobin ≥80 g/dL
Key exclusion criteria (1 listed)
- Central nervous system involvement Prior or concurrent malignant tumor that has not been cured, except adequately treated basal cell carcinoma of the skin, carcinoma in situ of the cervix, and superficial bladder cancer Presence of any of the following cardiovascular diseases: myocardial ischemia or myocardial infarction of grade II or above, uncontrolled arrhythmia (including QTc interval ≥450 ms in males and ≥470 ms in females), New York Heart Association (NYHA) class III-IV heart failure, or left ventricular ejection fraction (LVEF) <50% on echocardiography Coagulation abnormalities (INR >1.5, or prothrombin time (PT) >ULN + 4 seconds, or APTT >1.5×ULN), a bleeding tendency, or ongoing thrombolytic or anticoagulant therapy Arterial or venous thromboembolic events within 12 months before enrollment, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, and cerebral infarction), deep vein thrombosis, and pulmonary embolism Known hereditary or acquired bleeding or thrombotic diathesis (e.g., hemophilia, coagulation disorders) Major surgery, severe traumatic injury, fracture, or ulcer within 4 weeks before enrollment Factors that significantly affect the oral absorption of drugs, such as inability to swallow, chronic diarrhea, and intestinal obstruction Active infection requiring antimicrobial therapy (e.g., antibacterial or antiviral agents; excluding anti-HBV therapy for chronic hepatitis B and antifungal therapy) Active hepatitis B (HBV DNA ≥2000 IU/mL or 10⁴ copies/mL) or hepatitis C (positive anti-HCV antibody with HCV RNA above the lower limit of detection of the assay) History of psychotropic substance abuse that cannot be abstained from, or presence of a psychiatric disorder Known allergy to 68Ga-Pentixafor or 18F-FDG Inability to undergo PET/CT examination for other reasons (e.g., claustrophobia, inability to lie supine) Pregnant or lactating women; patients of childbearing potential who are unwilling or unable to use effective contraception Any other condition that, in the judgment of the investigator, may affect the conduct of the clinical study or the assessment of study results.
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 |
|---|---|---|
| OrelabrutinibAfter the patient received one cycle of the anti-CD20 monoclonal antibody CVP regimen, obinutuzumab was added starting from the second cycle for combination therapy. After a total of five cycles of the obinutuzumab combined with the anti-CD20 monoclonal antibody CVP regimen, maintenance treatment with obinutuzumab monotherapy was administered for 18 cycles or until disease progression or unacceptable toxicity occurred. | Drug | Patients with MZL who are treatment-naive |
Primary outcome
24-month progression-free survival rate
Time frame: From enrollment to 24 months
Percentage of patients alive and free from disease progression at 24 months (±4 weeks) after enrollment.
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 4 Nov 2026.
- Individual participant dataSharing planned: No
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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.
Xinxin Cao study chair
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
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 in people with Marginal Zone Lymphoma(MZL), run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences 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 10 inclusion and 1 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: under way, not looking for participants, as of the sponsor's last update on 4 Nov 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?
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?
24-month progression-free survival rate (time frame: From enrollment to 24 months). 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 4 Nov 2026.