Clinical Study of OR for Second-line Treatment of Refractory MZL

NCT ID: NCT06134284

Last Updated: 2024-06-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-02
• Study Completion Date: 2029-12-31

Brief Summary

The goal of this clinical trial is to test the overall response rate of Orelabrutinib combined with rituximab (OR regimen) for second-line treatment of relapsed/refractory marginal zone lymphoma.

Conditions

OR Regimen for Relapsed/Refractory Marginal Zone Lymphoma

Study Design

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

Study Groups

OR regimen

The specific medication regimen for the OR regimen is as follows: Orelabrutinib 150mg orally once daily; Rituximab 375mg/m² intravenous infusion, administered every 21 days.

Group Type: EXPERIMENTAL

Orelabrutinib combined with rituximab

Intervention Type: DRUG

This is a single-arm trial. Patients with relapsed/refractory marginal zone lymphoma will be treated with the OR regimen. The treatment plan is as follows: Orelabrutinib 150mg oral administration once a day, Day 1-21; Rituximab 375mg/m² intravenous infusion, Day 1. Each cycle is 21 days. PET-CT evaluation will be conducted after 4 cycles. If a partial response (PR) or better is achieved, the patient will receive further treatment with the OR regimen for an additional 4 cycles before transitioning to single-agent maintenance therapy with either rituximab or obinutuzumab. If a PR or better is not achieved after 4 cycles, the patient will discontinue from the trial.

Interventions

Orelabrutinib combined with rituximab

This is a single-arm trial. Patients with relapsed/refractory marginal zone lymphoma will be treated with the OR regimen. The treatment plan is as follows: Orelabrutinib 150mg oral administration once a day, Day 1-21; Rituximab 375mg/m² intravenous infusion, Day 1. Each cycle is 21 days. PET-CT evaluation will be conducted after 4 cycles. If a partial response (PR) or better is achieved, the patient will receive further treatment with the OR regimen for an additional 4 cycles before transitioning to single-agent maintenance therapy with either rituximab or obinutuzumab. If a PR or better is not achieved after 4 cycles, the patient will discontinue from the trial.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age: 18 years, 80, Sex gender no limitied;

2. histological confirmation of MZL, For splenic marginal zone lymphoma (SMZL) where histological specimens of the spleen were not available, Requirements to meet the minimum diagnostic criteria for SMZL, And exclude any other type of small B cell lymphoma, That is, requiring a definite diagnosis of MZL;

3. at least one two-dimensional measurable lymph node lesion (CT scan or MR / display maximum diameter> 1.5cm), Or at least one two-dimensional measurable extranodal lesion (CT scan or MRI showing maximum diameter> 1.0cm);

4. the investigator required systemic treatment for marginal zone lymphoma;

5. at least 1 previous course of systemic lymphoma treatment (including previous immunotherapy or chemoimmunotherapy), 3 without efficacy above PR after imaging evaluation, Or disease progression after effective treatment;

6. ECOG, physical strength score 0-2;

7. primary organ function meets the following criteria 7 days prior to treatment:

1. blood routine: absolute neutrophil ≥1.5x10^9 / L, Platelet≥ 75x10^9 / L, Hemoglobin≥75g / L; If the concomitant bone marrow invasion, Absolute neutrophil value ≥1.0x10^9 / L, Platelet≥50x10^9 / L, Hemoglobin≥ 50g / L;

2. Blood Chemistry: total bilirubin ≤1.5 times ULN, AST or ALT ≤2 times ULN; If the liver is infiltrated with a lymphoma, Then, ALT and AST ≤5 times ULN, Serum creatinine ≤ 1.5 times ULN or creatinine clearance ≥45 ml/min (Cockcroft-Gault formula); Serum amylase ≤ULN;

3. coagulation function: International normalized ratio (INR) ≤1.5 times ULN, Activated partial thromboplastin time (APTT)≤ 1.5 times ULN.

4. cardiac color ultrasound: left ventricular ejection fraction 50%;

8. expected survival time of 3 months;

9. for men who did not undergo sterilization: agree to use the barrier contraceptive method during treatment and for at least 3 months after the last administration of obutinib or rituximab or on the older) as required in the guidelines established by the institution. In addition, male patients must agree to request their spouses to use other methods of contraception (e. g., oral contraceptives, intrauterine devices, barrier contraception, or spermicide).

10. For women who did not undergo sterilization: at least 28 days prior to consent to start study medication, during treatment, or after last administration of obutinib or rituximab, such as oral contraceptives, intrauterine devices or barrier contraception;

11. voluntarily signed written informed consent before test screening.

Exclusion Criteria

1. The patient had been previously treated with obutinib in combination with rituximab, Efficacy was assessed as being refractory, Infraciness was defined as no remission (PR or CR) after start of treatment 4

2. history of severe allergy or allergic reaction to monoclonal antibody therapy

3. known to be allergic to any study drug

4. current or previous other malignancy, Unless curative treatment with no evidence of recurrence and metastasis in nearly 5 years;

5. lymphoma involvement of the central nervous system;

6. uncontrolled or important cardiovascular disease, Includes:

1. occurrence of New York Cardiology Association (NYHA) grade II or above congestive heart failure, unstable angina, myocardial infarction within 6 months prior to the first administration of study drug, Or the presence of significant arrhythmias requiring treatment at screening (e. g., persistent rapid AF, persistent ventricular tachycardia, ventricular fibrillation, tip torsion, history of second-degree II AV (AV) block, or history of third-degree AV block), Left ventricular ejection fraction (LVEF) <50%;

2. primary cardiomyopathy (e. g. dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, irregular cardiomyopathy);

3. history of clinically significant QTc interval extension, Or subjects with coronary heart disease with QTc interval female> 470ms and male> 450ms;

4. symptomatic or requiring medication;

5. difficult-to-control hypertension (on the basis of improved lifestyle, With an adequate amount of 2 or more antihypertensive drugs (including diuretics) for more than 1 month, Or take 4 or more antihypertensive drugs to effectively control blood pressure).

7. Active bleeding within the 2 months prior to screening, Or are taking anticoagulant drugs, Or if the investigator considers a definite bleeding tendency;

8. urine protein 2 +, And 24-hour urinary protein quantification of 2g / 24 hours;

9. a history of deep vein thrombosis or pulmonary embolism;

10. clinically obvious gastrointestinal abnormalities, May affect drug intake, transport, or absorption (e. g. inability to swallow, chronic diarrhea, intestinal obstruction, etc.), Or subjects with total gastrectomy;

11. history of organ transplantation or allogeneic bone marrow transplantation;

13. active infection or uncontrolled HBV (HBV DNA titer of 10 ^ 3 copies / ml), HCVAb positive, HI V/A IDS (Acquired Immune Deficiency Syndrome) or other serious infectious diseases;

14. subjects with current pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severe impairment of lung function, etc.;

15. Previous treatment with BTK, BCR, pathway inhibitors (such as PI3K, Syk), and BCL-2 kinase inhibitors;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lixia Sheng

OTHER

Sponsor Role: lead

Responsible Party

Lixia Sheng

hematology department

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Chen

Role: PRINCIPAL_INVESTIGATOR

First Affiliated Hospital of Ningbo University

Locations

The Second Affiliated Hospital of Zhejiang University, Ningbo First Hospital

Hangzhou, Zhejiang, China

Site Status: RECRUITING

86-574-87085596

Ningbo, Zhejiang, China

Site Status: RECRUITING

The First Affiliated Hospital of Ningbo University

Ningbo, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Lixia Sheng, Doctor

Role: CONTACT

slx800408@163.com

86-574-87085596 ext. 87085596

Chen

Role: CONTACT

nbyykyk@163.com

86-574-87085111

Facility Contacts

Wenbin Qian, Doctor

Role: primary

qianwb@zju.edu.cn

86-571-87581969

Lixia Sheng, doctor

Role: primary

slx800408@163.com

86-574-87085596

Lixia Sheng, doctor

Role: primary

slx800408@163.com

86-574-87085596

Other Identifiers

Ningbo102

Identifier Type: -

Identifier Source: org_study_id