Orelabrutinib Combined With Rituximab Versus R-CVP in the Untreated MZL： A Randomized, Open Phase II Trial

NCT06700798 | Recruiting Phase 2

• 1 other identifier: ORRIS
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Marginal Zone Lymphoma(MZL)

Keywords

Orelabrutinib combined with Rituximab versus R-CVP

Outcome Measures

Primary Outcomes (1)

• CRR

  The proportion of patients who achieve Complete Remission (CR) at the end of the combined antitumor treatment

  up to two years

Secondary Outcomes (3)

• ORR

  up to two years

• PFS rate at 24month

  Two years after the last patient was enrolled.

• Safety parameters

  up to 3 years

Study Arms (2)

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

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.

Drug: rituximab; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Prednisone tablet

Interventions

Orelabrutinib DRUG

150mg po

Also known as: ICP-022

OR-R

rituximab DRUG

375mg/m\^2, intravenous

OR-R; R-CVP

Cyclophosphamide DRUG

750mg/m\^2

R-CVP

Vincristine DRUG

1.4mg/m\^2

R-CVP

Prednisone tablet DRUG

60mg/m\^2

R-CVP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.);
• 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.

Sponsors & Collaborators

• Fei Li: lead

Study Sites (1)

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330000, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal Zone

Interventions

orelabrutinib; Rituximab; Cyclophosphamide; Vincristine; Prednisone

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Fei Li, professor

  The First Affiliated Hospital of Nanchang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yulan Zhou Doctor, PhD

CONTACT

86-0791-88692743; wenxin_yl@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief physician

Study Record Dates

• First Submitted: November 20, 2024
• First Posted: November 22, 2024
• Study Start: December 1, 2024
• Primary Completion: May 4, 2026
• Study Completion (Estimated): December 4, 2027
• Last Updated: June 17, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)