Marginal Zone Lymphoma(MZL)Phase 2NCT06700798
Orelabrutinib Combined With Rituximab Versus R-CVP in the Untreated MZL： A Randomized, Open Phase II Trial
A Phase 2 study testing Orelabrutinib, rituximab and Cyclophosphamide in people with Marginal Zone Lymphoma(MZL), run by Fei Li at 1 site in China.
Trial summary
This study is a randomized, open-label, multicenter, prospective clinical trial aimed at evaluating the efficacy and safety of orelabrutinib combined with rituximab for the previously untreat MZL Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Marginal Zone Lymphoma(MZL)
- What is being tested?
- Orelabrutinib, rituximab and Cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteChina
- Study dates
- 1 Dec 2024to 4 Dec 2027
- 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
- 1.Age ≥18 years； 2.ECOG performance status level 0~2； 3.Life expectancy of at least 12 weeks; 4.Confirmed CD20-positive marginal zone lymphoma according to the WHO 2008 lymphoma classification criteria, including splenic MZL, nodal MZL, and extranodal MZL subtypes; 5.Measurable lesions detected by enhanced computed tomography (CT) or magnetic resonance imaging (MRI); 6.Indication for treatment according to NCCN guidelines and no prior systemic treatment for MZL; 7.Normal function of major organs; 8.Women of childbearing age must have taken reliable contraceptive measures or undergone a pregnancy test (serum or urine) within 7 days before enrollment, with a negative result, and must be willing to use appropriate contraceptive methods during the trial period and for 8 weeks after the last administration of the trial medication. For men, they must agree to use appropriate contraceptive methods during the trial period and for 8 weeks after the last administration of the trial medication or have undergone surgical sterilization; 9.The subject voluntarily participates in this study, signs the informed consent form, has good compliance, and cooperates with follow-up.
- -
Who cannot join
- Patients with central nervous system involvement;
- History or concurrent other untreated malignant tumors, except for cured basal cell carcinoma of the skin, cervical carcinoma in situ, and superficial bladder cancer;
- Patients with the following cardiovascular diseases: Grade II or above myocardial ischemia or myocardial infarction, poorly controlled arrhythmias (including QTc interval for males ≥450 ms, for females ≥470 ms); Class III to IV heart failure according to NYHA standards, or echocardiography indicating left ventricular ejection fraction (LVEF) <50%;
- Coagulation abnormalities (INR >1.5 or prothrombin time (PT) >ULN+4 seconds or APTT >1.5 ULN), with a tendency to bleed or undergoing thrombolytic or anticoagulant therapy;
- Arterial/venous thrombotic events within 12 months prior to enrollment, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
- Known hereditary or acquired bleeding and thrombotic tendencies (such as hemophilia, coagulation disorders, thrombocytopenia, hypersplenism, etc.);
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- Major surgical procedures or severe traumatic injuries, fractures, or ulcers within 4 weeks prior to enrollment;
- Factors that significantly affect the absorption of oral medications, such as inability to swallow, chronic diarrhea, and intestinal obstruction;
- Active infections requiring antimicrobial treatment (e.g., requiring antibacterial, antiviral drugs, excluding chronic hepatitis B antiviral treatment, antifungal treatment);
- Active hepatitis B (HBV DNA ≥2000 IU/mL or 104 copies/mL) or hepatitis C (hepatitis C antibody positive, and HCV RNA above the lower limit of detection of the analytical method);
- History of substance abuse and inability to quit or mental disorders;
- Participation in other anticancer drug clinical trials within 4 weeks prior to enrollment;
- Received treatment with potent CYP3A4 inhibitors within 7 days prior to enrollment, or received treatment with potent CYP3A4 inducers within 12 days prior to study participation;
- Pregnant or breastfeeding women; patients of childbearing potential who are unwilling or unable to use effective contraceptive measures;
- Other situations judged by the investigator that may affect the conduct of the clinical study and the determination of study results.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
The First Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, 330000
Yulan Zhou doctor, PhD, 86-0791-88692748, wenxin_yl@163.com
About this study
Official title: A Randomized, Open-Label Phase II Clinical Study of Orelabrutinib Combined With Rituximab Versus R-CVP in the Treatment of Newly Diagnosed Marginal Zone Lymphoma (MZL).
This study is a randomized, open-label, multicenter, prospective clinical trial aimed at evaluating the efficacy and safety of orelabrutinib combined with rituximab for the previously untreat MZL
Read the detailed description
For patients with advanced-stage MZL who require treatment, immunochemotherapy is the standard therapy, including regimens such as BR, R-CHOP, R-CVP, etc. The second-generation BTK inhibitor, orelabrutinib, has shown promising efficacy in relapsed/refractory MZL, suggesting that a chemofree regimen combining orelabrutinib with rituximab could also achieve good clinical outcomes in first-line treatment of MZL. However, there is still a lack of prospective studies to confirm this. This study plans to compare the efficacy and safety of orelabrutinib combined with rituximab followed by maintenance therapy with orelabrutinib to the R-CVP regimen.
- Conditions
- Marginal Zone Lymphoma(MZL)
- Being tested
- Orelabrutinib, rituximab, Cyclophosphamide, Vincristine, Prednisone tablet
- Keywords
- Orelabrutinib combined with Rituximab versus R-CVP
- 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
Also called ICP-022
150mg po
rituximabDrug
375mg/m^2, intravenous
CyclophosphamideDrug
750mg/m^2
VincristineDrug
1.4mg/m^2
Prednisone tabletDrug
60mg/m^2
| Study group | Role | What they receive |
|---|---|---|
| OR-R | Experimental | Orelabrutinib 150mg, oral, once daily, Days 1-28, with a cycle of 4 weeks; Cycles 1-24； Rituximab: 375mg/m^2, intravenous, Day 1, with a cycle of 4 weeks; Cycles 1-6 Receives: Drug: Orelabrutinib; Drug: rituximab |
| R-CVP | Active comparator | Rituximab: 375mg/m^2, intravenous, Day 1, with a cycle of 3 weeks; Cycles 1-8； Cyclophosphamide: 750mg/m^2, intravenous, Day 1, with a cycle of 3 weeks;Cycles 1-8； Vincristine: 1.4mg/m^2 (maximum 2mg), intravenous, Day 1, with a cycle of 3 weeks;Cycles 1-8； Prednisone: 60mg/m^2, oral, Days 1-5, with a cycle of 3 weeks，Cycles 1-8
Subsequently, maintenance with rituximab monotherapy until two years from the start of treatment or until toxicity intolerable. Receives: Drug: rituximab; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Prednisone tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
CRR
The proportion of patients who achieve Complete Remission (CR) at the end of the combined antitumor treatment
Measured: up to two years
Secondary outcomes (3)
ORR
ORR is defined as the percentage of participants with partial or complete response
Measured: up to two years
PFS rate at 24month
the proportion of patients who have not experienced disease progression or death due to any cause within 2 years of receiving the first dose of the study medication.
Measured: Two years after the last patient was enrolled.
Safety parameters
Type, frequency, and severity of AEs
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 posted22 Nov 2024
- Study start1 Dec 2024
- Primary completion4 May 2026 (estimated)
- Study completion4 Dec 2027 (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.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fei Li
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Fei Li, The First Affiliated Hospital of Nanchang University
- Investigators
- Fei Li, professor, Principal investigator, The First Affiliated Hospital of Nanchang University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06700798
- Sponsor's protocol ID
- ORRIS
- Status last verified
- Jun 2025
- First submitted
- 20 Nov 2024
- Last updated
- 17 Jun 2025
- Results posted
- No
- Data monitoring committee
- 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 17 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-Label Phase II Clinical Study of Orelabrutinib Combined With Rituximab Versus R-CVP in the Treatment of Newly Diagnosed Marginal Zone Lymphoma (MZL).
- ClinicalTrials.gov ID
- NCT06700798
- Acronym / sponsor ID
- ORRIS
- Conditions
- Marginal Zone Lymphoma(MZL)
- Keywords
- Orelabrutinib combined with Rituximab versus R-CVP
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Fei LiUniversity, hospital or other
- Study start
- 1 Dec 2024 (actual)
- Primary completion
- 4 May 2026 (estimated)
- Study completion
- 4 Dec 2027 (estimated)
- First posted
- 22 Nov 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 study is a randomized, open-label, multicenter, prospective clinical trial aimed at evaluating the efficacy and safety of orelabrutinib combined with rituximab for the previously untreat MZL
Detailed description
For patients with advanced-stage MZL who require treatment, immunochemotherapy is the standard therapy, including regimens such as BR, R-CHOP, R-CVP, etc. The second-generation BTK inhibitor, orelabrutinib, has shown promising efficacy in relapsed/refractory MZL, suggesting that a chemofree regimen combining orelabrutinib with rituximab could also achieve good clinical outcomes in first-line treatment of MZL. However, there is still a lack of prospective studies to confirm this. This study plans to compare the efficacy and safety of orelabrutinib combined with rituximab followed by maintenance therapy with orelabrutinib to the R-CVP regimen.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| OR-R | Experimental | Drug: Orelabrutinib, Drug: rituximabOrelabrutinib 150mg, oral, once daily, Days 1-28, with a cycle of 4 weeks; Cycles 1-24； Rituximab: 375mg/m^2, intravenous, Day 1, with a cycle of 4 weeks; Cycles 1-6 |
| R-CVP | Active comparator | Drug: rituximab, Drug: Cyclophosphamide, Drug: Vincristine, Drug: Prednisone tabletRituximab: 375mg/m^2, intravenous, Day 1, with a cycle of 3 weeks; Cycles 1-8； Cyclophosphamide: 750mg/m^2, intravenous, Day 1, with a cycle of 3 weeks;Cycles 1-8； Vincristine: 1.4mg/m^2 (maximum 2mg), intravenous, Day 1, with a cycle of 3 weeks;Cycles 1-8； Prednisone: 60mg/m^2, oral, Days 1-5, with a cycle of 3 weeks，Cycles 1-8 Subsequently, maintenance with rituximab monotherapy until two years from the start of treatment or until toxicity intolerable. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 1.Age ≥18 years； 2.ECOG performance status level 0~2； 3.Life expectancy of at least 12 weeks; 4.Confirmed CD20-positive marginal zone lymphoma according to the WHO 2008 lymphoma classification criteria, including splenic MZL, nodal MZL, and extranodal MZL subtypes; 5.Measurable lesions detected by enhanced computed tomography (CT) or magnetic resonance imaging (MRI); 6.Indication for treatment according to NCCN guidelines and no prior systemic treatment for MZL; 7.Normal function of major organs; 8.Women of childbearing age must have taken reliable contraceptive measures or undergone a pregnancy test (serum or urine) within 7 days before enrollment, with a negative result, and must be willing to use appropriate contraceptive methods during the trial period and for 8 weeks after the last administration of the trial medication. For men, they must agree to use appropriate contraceptive methods during the trial period and for 8 weeks after the last administration of the trial medication or have undergone surgical sterilization; 9.The subject voluntarily participates in this study, signs the informed consent form, has good compliance, and cooperates with follow-up.
- -
Key exclusion criteria (15 listed)
- Patients with central nervous system involvement;
- History or concurrent other untreated malignant tumors, except for cured basal cell carcinoma of the skin, cervical carcinoma in situ, and superficial bladder cancer;
- Patients with the following cardiovascular diseases: Grade II or above myocardial ischemia or myocardial infarction, poorly controlled arrhythmias (including QTc interval for males ≥450 ms, for females ≥470 ms); Class III to IV heart failure according to NYHA standards, or echocardiography indicating left ventricular ejection fraction (LVEF) <50%;
- Coagulation abnormalities (INR >1.5 or prothrombin time (PT) >ULN+4 seconds or APTT >1.5 ULN), with a tendency to bleed or undergoing thrombolytic or anticoagulant therapy;
- Arterial/venous thrombotic events within 12 months prior to enrollment, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
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 |
|---|---|---|
| OrelabrutinibAlso: ICP-022150mg po | Drug | OR-R |
| rituximab375mg/m^2, intravenous | Drug | OR-R, R-CVP |
| Cyclophosphamide750mg/m^2 | Drug | R-CVP |
| Vincristine1.4mg/m^2 | Drug | R-CVP |
| Prednisone tablet60mg/m^2 | Drug | R-CVP |
Primary outcome
CRR
Time frame: up to two years
The proportion of patients who achieve Complete Remission (CR) at the end of the combined antitumor treatment
3 secondary outcomes
ORR
Time frame: up to two years
PFS rate at 24month
Time frame: Two years after the last patient was enrolled.
Safety parameters
Time frame: 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 17 Jun 2025.
- 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.
Fei Li, professor principal investigator
The First Affiliated Hospital of Nanchang University
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, rituximab and Cyclophosphamide in people with Marginal Zone Lymphoma(MZL), run by Fei Li 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 2 inclusion and 15 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 17 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 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 Yulan Zhou Doctor, PhD (86-0791-88692743, wenxin_yl@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CRR (time frame: up to two years). 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 17 Jun 2025.