Prospective Clinical Study of Orelabrutinib in Combination With Rituximab (OR) for Primary Marginal Zone Lymphoma (MZL) That Failed or Not Suitable for Local Therapy

NCT ID: NCT06478472

Last Updated: 2024-07-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-06-23
• Study Completion Date: 2027-06-23

Brief Summary

Orelabrutinib combined with rituximab (OR) therapy were used to assess the efficacy and safety for newly diagnosed Marginal zone cell lymphoma

Conditions

Marginal Zone Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

OR

Orelabrutinib in combination with rituximab

Group Type: EXPERIMENTAL

Orelabrutinib in combination with rituximab

Intervention Type: DRUG

Induction Phase:

Orelabrutinib + rituximab for a total of 6 cycles of 28 days each Obrutinib (O) 150mg oral d1-28 Rituximab (R) 375mg/m2 IV d0

Maintenance phase:

Orelabrutinib 150mg po qd 24 cycles of 28 days each

Interventions

Orelabrutinib in combination with rituximab

Induction Phase:

Orelabrutinib + rituximab for a total of 6 cycles of 28 days each Obrutinib (O) 150mg oral d1-28 Rituximab (R) 375mg/m2 IV d0

Maintenance phase:

Orelabrutinib 150mg po qd 24 cycles of 28 days each

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age: ≥18 years old, gender is not limited;

2. Histopathologically confirmed CD20-positive marginal zone lymphoma including MALT, SMZL, NMZL;

3. Indications for treatment: impact on organ function, development of symptoms associated with lymphoma, large masses, hematopenia secondary to lymphoma;

4. MZL that has progressed, relapsed, or is unsuitable for local therapy after prior local therapy (local therapy includes surgery, radiotherapy, anti-Helicobacter pylori therapy, anti-hepatitis C therapy);

5. ECOG 0-2;

6. Must have at least one measurable or evaluable lesion using the Lugano 2014 Lymphoma Efficacy Evaluation Criteria: i.e., PET/CT with an evaluable lesion; an intranodal lesion with a long diameter greater than 1.5 cm and a short diameter greater than 1.0 cm or an extranodal lesion with a long diameter of > 1.0 cm, as assessed by CT or MR

7. Participants with splenic MZL who do not meet the above criteria for radiologically measurable disease are eligible, provided that the bone marrow infiltration of the MZL is histologically confirmed;

8. HBV-positive serology (concealed carriers: anti-HBeAg +, HbsAg-, anti-HBsAg +/-) are eligible for enrollment only if they have a negative HBV-DNA test;

9. Major organ function meets the following criteria: a) Blood routine: absolute neutrophil value ≥1.5×109/L, platelet ≥75×109/L, hemoglobin ≥75g/L; if accompanied by bone marrow invasion, absolute neutrophil value ≥1.0×109/L, platelet ≥50×109/L, hemoglobin ≥50g/L; b) Blood biochemistry: total bilirubin ≤1.5 times the 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. 10) Expected survival ≥ 3 months;

10. Voluntary written informed consent prior to trial screening.

Exclusion Criteria

1. Lymphoma with CNS involvement or high grade transformation;

2. HIV-positive patients and or HCV-active infection (documented by HCV-RNA-positive test);

3. History of deep vein thrombosis or pulmonary embolism within the last 6 months;

4. Active bleeding within 2 months prior to screening, or taking anticoagulant medications, or in the opinion of the investigator, a definite bleeding tendency

5. Continuous use of drugs with moderate to severe inhibition or strong induction of cytochrome P450 CYP3A;

6. Severe chronic obstructive pulmonary disease (COPD) with hypoxemia.

7. Active bacterial, fungal, or viral infections uncontrolled by systemic therapy;

8. In addition to cured basal cell carcinoma of the skin or cervical cancer in situ or early prostate cancer not requiring systemic therapy, or early breast cancer requiring surgery alone. Other malignant tumors within the last 2 years or concurrently;

9. Uncontrolled or significant cardiovascular disease, including: a) New York Heart Association (NYHA) Class II or higher congestive heart failure, unstable angina, myocardial infarction within 6 months prior to the first dose of study drug, or an arrhythmia requiring treatment with a left ventricular ejection fraction (LVEF) of <50% at the time of Screening; b) primary cardiomyopathies (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, hypertrophic cardiomyopathy, cardiomyopathy, cardiomyopathy, cardiomyopathy, cardiomegaly, cardiomyopathy, cardiomegaly) b) Primary cardiomyopathies (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, indeterminate cardiomyopathy); c) A history of clinically significant prolongation of the QTc interval, or QTc intervals of >470 ms in women and >450 ms in men at Screening; d) Subjects with symptomatic or medically-treated coronary artery heart disease; e) Subjects with difficult-to-control high blood pressure (as determined by a reasonable and tolerable dose of adequate medications based on lifestyle improvement). (blood pressure remains uncontrolled for more than 1 month despite the application of a reasonably tolerable and adequate dose of 3 or more antihypertensive medications (including diuretics) on the basis of lifestyle improvement, or blood pressure is not effectively controlled until 4 or more antihypertensive medications have been administered);

10. Subjects with clinically significant gastrointestinal abnormalities that may interfere with drug ingestion, transit, or absorption (e.g., inability to swallow, chronic diarrhea, intestinal obstruction, etc.), or total gastrectomy;

11. Major surgery within 6 weeks prior to screening or minor surgery within 2 weeks prior to screening. A major surgical procedure is one in which general anesthesia is used, but endoscopy for diagnostic purposes is not considered a major surgical procedure. Insertion of vascular access devices will be exempt from this exclusion criterion; ;

12. Subjects who use drugs or alcohol;

13. Pregnant, lactating females and subjects of childbearing age who do not wish to use contraception;

14. known hypersensitivity or allergic reaction to murine antibodies or proteins

15. Any mental or cognitive impairment that may limit understanding, implementation, and compliance with the informed consent form;

16. Previous treatment with BTK, BCR pathway inhibitors (e.g., PI3K, Syk), and BCL-2 inhibitors.

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

Sponsors

The First Hospital of Jilin University

OTHER

Sponsor Role: collaborator

Fujian Cancer Hospital

OTHER_GOV

Sponsor Role: collaborator

Guangdong Provincial People's Hospital

OTHER

Sponsor Role: collaborator

Nanfang Hospital, Southern Medical University

OTHER

Sponsor Role: collaborator

The Second Affiliated Hospital of Dalian Medical University

OTHER

Sponsor Role: collaborator

Jiangxi Provincial Cancer Hospital

OTHER

Sponsor Role: collaborator

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

OTHER

Sponsor Role: collaborator

Shaanxi Provincial Cancer Hospital

OTHER

Sponsor Role: collaborator

Chinese PLA General Hospital

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital of Xiamen University

OTHER

Sponsor Role: lead

Responsible Party

Bing, Xu

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bing Xu

Role: PRINCIPAL_INVESTIGATOR

The First Aiffiliated hosptical of xiamen University

Locations

Bing, Xu

Xiamen, Fujian, China

Site Status: RECRUITING

Countries

China

Central Contacts

Bing Xu, PhD

Role: CONTACT

xubingzhangjian@126.com

18750918842

Facility Contacts

Bing Xu

Role: primary

Other Identifiers

XMDYYYXYK-09

Identifier Type: -

Identifier Source: org_study_id