MZL-IPI Risk-adapted Targeted Therapy in Untreated MZL

NCT ID: NCT06793189

Last Updated: 2025-01-27

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 145 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-21
• Study Completion Date: 2028-12-31

Brief Summary

Marginal zone lymphoma (MZL) is a common type of indolent lymphoma that originates from the marginal zone of lymphoid follicles. This study aims to evaluate targeted therapy based on the prognostic risk stratification of MZL-IPI in newly diagnosed MZL cases requiring systemic treatment, and provides a basis for precision treatment of MZL.

Conditions

Marginal Zone Lymphoma(MZL)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Obinutuzumab and Orelabrutinib (O2) regimen

Low-risk patients (MZL-IPI 0-2 points)

Group Type: EXPERIMENTAL

Obinutuzumab and Orelabrutinib

Intervention Type: DRUG

Induction: Obinutuzumab (1000 mg on days 1, 8, and 15 of cycle 1; 1000 mg on day 1 of cycles 2-6, cycle length=21 days) and Orelabrutinib (150 mg once daily).

Orelabrutinib

Intervention Type: DRUG

Maintenance: Orelabrutinib monotherapy (150 mg once daily up to 24 months).

Obinutuzumab, Orelabrutinib and Lenalidomide (O2R) regimen

High-risk patients (MZL-IPI 3-5 points)

Group Type: EXPERIMENTAL

Obinutuzumab, Orelabrutinib and Lenalidomide

Intervention Type: DRUG

Induction: Obinutuzumab (1000 mg on days 1, 8, and 15 of cycle 1; 1000 mg on day 1 of cycles 2-6, cycle length=21 days), Orelabrutinib (150 mg once daily), and Lenalidomide (25 mg on days 2-11 of cycles 1-6, cycle length=21 days).

Orelabrutinib

Intervention Type: DRUG

Maintenance: Orelabrutinib monotherapy (150 mg once daily up to 24 months).

Interventions

Obinutuzumab and Orelabrutinib

Induction: Obinutuzumab (1000 mg on days 1, 8, and 15 of cycle 1; 1000 mg on day 1 of cycles 2-6, cycle length=21 days) and Orelabrutinib (150 mg once daily).

Intervention Type: DRUG

Obinutuzumab, Orelabrutinib and Lenalidomide

Induction: Obinutuzumab (1000 mg on days 1, 8, and 15 of cycle 1; 1000 mg on day 1 of cycles 2-6, cycle length=21 days), Orelabrutinib (150 mg once daily), and Lenalidomide (25 mg on days 2-11 of cycles 1-6, cycle length=21 days).

Intervention Type: DRUG

Orelabrutinib

Maintenance: Orelabrutinib monotherapy (150 mg once daily up to 24 months).

Intervention Type: DRUG

Orelabrutinib

Maintenance: Orelabrutinib monotherapy (150 mg once daily up to 24 months).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 1. Histopathologically confirmed CD20-positive marginal zone lymphoma (according to the 2016 WHO classification).

2. Age ≥ 18 years old, regardless of gender. 3. MZL patients requiring systemic treatment, including but not limited to:

1. Helicobacter pylori (HP)-positive or HP - negative gastric mucosa extranodal marginal zone lymphoma (MALT) patients with progression/relapse after local treatment (including surgery, radiotherapy, and anti - Helicobacter pylori treatment).

2. Non - gastric MALT patients with Ann Arbor stage I - II who have progression/relapse after local treatment (including surgery, radiotherapy, etc.), or untreated patients with Ann Arbor stage III - IV who meet the GELF criteria recommended by the NCCN guidelines.

3. Splenic marginal zone lymphoma (SMZL) patients with progression/relapse after local treatment (including splenectomy, antiviral treatment for HCV - positive patients, etc.), or untreated patients meeting the criteria of progressive or painful splenomegaly, symptomatic or progressive cytopenia such as HB < 100g/L, PLT < 80×10⁹/L, absolute neutrophil count (ANC) < 1.0×10⁹/L.

4. Nodal marginal zone lymphoma (NMZL) patients with Ann Arbor stage I - II who have progression/relapse after local treatment (including surgery, radiotherapy, etc.), or untreated patients with Ann Arbor stage III - IV who meet the GELF criteria recommended by the NCCN guidelines.

4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2. 5. Life expectancy of at least 3 months. 6. The patient has adequate bone marrow (except those caused by MZL), liver and kidney functions.

7. Able to comply with the research procedures and cooperate in the implementation of the entire research process; 8. Written informed consent; 9. Women with fertility agree to take appropriate measures to avoid pregnancy during the treatment period until at least one year after the end of treatment; Men agree to maintain abstinence or use barrier contraception.

Exclusion Criteria

• 1. Histologically transformed into high-grade lymphoma. 2. Known central nervous system involvement of MZL. 3. Previous systemic treatment including immunotherapy, chemotherapy or targeted drugs.

4. Previous autologous stem-cell transplantation or allogeneic tissue/solid organ transplantation.

5. History of other invasive cancers within the past 3 years that have not received curative treatment or are still receiving anti-cancer treatment (including hormonal therapy for breast or prostate cancer).

6. Complicated with uncontrolled cardiovascular and cerebrovascular diseases (such as New York Heart Association-defined grade 3 or 4 heart failure, arrhythmia, myocardial infarction, stroke, or intracranial hemorrhage), coagulation - disorder diseases, connective tissue diseases, severe infectious diseases (including active pulmonary tuberculosis), etc.

7. Known human immunodeficiency virus (HIV) infection, or active hepatitis B or C virus infection (positive result shown by polymerase chain reaction [PCR]). Serological antibody - positive is allowed if HBV DNA < 10³ IU/ml; HCV RNA test must be negative.

8. Vaccinated with live attenuated vaccines within 4 weeks before starting investigational treatment. During the study, patients are prohibited from receiving live attenuated vaccine inoculations, including influenza vaccines.

9. Requiring continuous treatment with potent and moderate-effect CYP3A inhibitors or CYP3A inducers.

10. Unable to swallow capsules or having diseases that significantly affect gastrointestinal function, such as malabsorption syndrome, bariatric surgery, inflammatory bowel disease, or partial or complete intestinal obstruction.

11. Psychiatric patients or other patients known or suspected to be unable to fully comply with the study protocol.

12. Pregnant or lactating women. 13. Other concurrent and uncontrolled medical conditions that, in the investigator's opinion, will affect the patient's participation in the study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ruijin Hospital

OTHER

Sponsor Role: lead

Responsible Party

Zhao Weili

Professor and Director，Shanghai Institute of Hematology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Weili Zhao

Role: CONTACT

zwl_trial@163.com

+862164370045

Pengpeng Xu

Role: CONTACT

pengpeng_xu@126.com

+862164370045

Other Identifiers

MAGIC

Identifier Type: -

Identifier Source: org_study_id