Efficacy and Safety of Rituximab Plus Zanubrutinib and Lenalidomide for Relapsed and Refractory Diffuse Large B Cell Lymphoma, a Multicenter, Open and Prospective Clinical Trial

NCT ID: NCT05392257

Last Updated: 2022-05-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-01
• Study Completion Date: 2024-05-01

Brief Summary

This clinical trial is an investigator-initiated multicenter, open, prospective clinical study in order to explore the efficacy and safety of rituximab plus zanubrutinib and lenalidomide in relapsed and refractory diffuse large B cell lymphoma.

Detailed Description

Subjects are patients withRelapsed and refractory Diffuse Large B cell lymphoma (DLBCL). All included patients will be treated with rituximab plus zanubrutinib and lenalidomide. In the induction stage, patients will receive 375 mg/m2 rituximab Day 1 of Cycles 1-6, twice-daily 160 mg zanubrutinib and 25 mg lenalidomide Days 1-21 of each 28-day cycle. In the maintenance treatment period, patients will receive 375 mg/m2 rituximab every 2 months, twice-daily 160 mg zanubrutinib and 10 mg lenalidomide Days 1-21 of each 28-day cycle. Imaging evaluation will take every two cycles to determine the best therapeutic effect, PD patients will exit from the clinical trial. The comprehensive therapeutic evaluating will take after 4 cycles. Peripheral blood stem cells can be collected from young patients with PR or CR. If patients' condition is suitable after 6 cycles of induction therapies, autologous hematopoietic stem cell transplantation can be chosed for patients with PR or CR and exit from the trail.Primary study endpoint is objective response rate (ORR) at the end of 6 cycles of induction therapy. Secondary study endpoints include progression-free survival time (PFS), overall survival (OS) and adverse reaction events (TEAS). After sample size calculation, we plan to enroll 72 relapsed and refractory diffuse large B cell lymphoma patients.

Conditions

Overall Survival

Study Design

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

Study Groups

Arms

Group Type: EXPERIMENTAL

Rituximab + zanubrutinib + lenalidomide

Intervention Type: DRUG

Rituximab at 375mg / m2, Day 0; Zanubrutinib 160mg bid continuously oral; Lenalidomide 25mg qd oral on days 1-21; 28 days as a course of treatment

Interventions

Rituximab + zanubrutinib + lenalidomide

Rituximab at 375mg / m2, Day 0; Zanubrutinib 160mg bid continuously oral; Lenalidomide 25mg qd oral on days 1-21; 28 days as a course of treatment

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

11．Before starting treatment, two pregnancy tests (at least one of them should be a serological pregnancy test) should be performed and the result must be negative.The first test must be conducted within 10-14 days before lenalidomide treatment, and the second test should within 24 hours before lenalidomide treatment.

12．Fertile women must agree to use reliable contraception from 4 weeks before lenalidomide treatment to at least 90 days after the last administration of zanubrutinib and lenalidomide, or 12 months after the last administration of rituximab (whichever is longer as the standard). Male patients taking the study drug may not donate sperm throughout the study.

13．Patients are not allowed to donate blood during lenalidomide treatment and within 4weeks after withdrawal, as blood may be used in pregnant female patients whose fetus will not be exposed to lenalidomide.

6．History of other active malignant diseases within 2 years prior to study entry, but the following situation are eligibility for inclusion: 1) adequately treated carcinoma in situ of the cervix; 2) Local basal cell carcinoma or squamous cell carcinoma of the skin; 3) Pre-existing malignant disease that has been controlled and treated locally and radically (surgically or otherwise).

7．Have clinically significant cardiovascular disease, including: 1) myocardial infarction that occurred within 6 months prior to screening stage; 2) Unstable angina pectoris within 3 months before screening stage; 3) Clinical major arrhythmia (e.g., persistent ventricular tachycardia, ventricular fibrillation, tachycardia with torsional tip); 4) QTcF (corrected according to Fridericia formula) >480 msec; 5) History of second-degree type II atrioventricular block or third-degree ATrioventricular block; 6) Class III or IV congestive heart failure as defined by the New York Heart Association (NYHA).

8．History of severe hemorrhagic disease, such as hemophilia A, hemophilia B, von willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention.

9．History of stroke or intracranial hemorrhage within 6 months prior to the first taking of the investigational drug.

10．Inability to swallow capsules or a medical condition that significantly affects gastrointestinal function, such as malabsorption syndrome, gastrectomy or small bowel resection, symptomatic inflammatory bowel disease, or partial or complete intestinal obstruction; 11．Uncontrolled systemic infection requiring intravenous administration of drugs for parenteral anti-infective therapy.

12．Human immunodeficiency virus (HIV) infection, or presence of serological status of active hepatitis B or C virus infection: 1）Either hepatitis B surface antigen (HBsAg) positive or hepatitis B core antibody (HBcAb) positive serology can be enrolled if hepatitis B virus (HBV) DNA (<20 IU/mL) and are willing to receive monthly HBV reactivation monitoring. 2) For patients in the presence of hepatitis C virus antibody, they could be enrolled if HCV RNA is not detected.

13．Hypersensitivity is known to either lenalidomide or rituximab, or to chemical or biological analogues of lenalidomide and rituximab.

14．Women during pregnancy or lactation. 15．Any life-threatening disease, medical condition, or incomplete organ system as considered by the investigator that may affect the safety of the subject or lead to the study risk.

16．History of deep venous thrombosis (DVT) or pulmonary embolism (PE) in the past 12 months.

-

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

Sponsors

Qingdao Central Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Qingdao central Hospital

Qingdao, Shandong, China

Site Status: RECRUITING

Countries

China

Facility Contacts

Ling Wang, MD

Role: primary

wldoctor@126.com

053268665401

Other Identifiers

QDCH20220521

Identifier Type: -

Identifier Source: org_study_id