A Study of Zanubrutinib in Combination With Polatuzumab Vedotin, Bendamustine and Rituximab in the Treatment of Relapsed/Refractory Diffuse Large B-cell Lymphoma

NCT ID: NCT06554600

Last Updated: 2024-08-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-31
• Study Completion Date: 2028-08-31

Brief Summary

This is a prospective, multicenter, single-arm, open phase II study to explore the efficacy and safety of Zanubrutinib in combination with Polatuzumab Vedotin, bendamustine, and rituximab (Polo-ZBR) in subjects with relapsed/refractory diffuse large B-cell lymphoma. Subjects with relapsed/refractory DLBCL who met the inclusion/exclusion criteria were screened and treated with 4 courses of Pola-ZBR regimen after signing informed consent. Subjects achieving PR or CR were consolidated with autologous transplantation consolidation or the original regimen for 2 additional courses, and then given Zanubrutinib maintenance therapy for 1 year. The final follow-up was observed until 2 years after enrollment.

Conditions

Refractory or Relapsed Diffuse Large B Cell Lymphoma

Study Design

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

Study Groups

Pola-ZBR treatment

Relapsed/refractory DLBCL were treated with 4 courses of Pola-ZBR regimen. Subjects achieving PR or CR were consolidated with autologous transplantation consolidation or the original regimen for 2 additional courses, and then given Zanubrutinib maintenance therapy for 1 year.

Group Type: EXPERIMENTAL

Zanubrutinib

Intervention Type: DRUG

160mg bid PO（d0-d20）

Polatuzumab Vedotin

Intervention Type: DRUG

Participants will receive a total of 4-6 cycles (a cycle being 21 days) of 1.8mg/kg Polatuzumab Vedotin on Day 2 of each cycle.

Bendamustine

Intervention Type: DRUG

Participants will receive a total of 4-6 cycles (a cycle being 21 days) of 70 mg/m2 Bendamustine on Days 2 and 3 of each cycle.

Rituximab

Intervention Type: DRUG

Participants will receive a total of 4-6 cycles (a cycle being 21 days) of 375 mg/m2 Rituximab on Day 1 of each cycle.

Interventions

Zanubrutinib

160mg bid PO（d0-d20）

Intervention Type: DRUG

Polatuzumab Vedotin

Participants will receive a total of 4-6 cycles (a cycle being 21 days) of 1.8mg/kg Polatuzumab Vedotin on Day 2 of each cycle.

Intervention Type: DRUG

Bendamustine

Participants will receive a total of 4-6 cycles (a cycle being 21 days) of 70 mg/m2 Bendamustine on Days 2 and 3 of each cycle.

Intervention Type: DRUG

Rituximab

Participants will receive a total of 4-6 cycles (a cycle being 21 days) of 375 mg/m2 Rituximab on Day 1 of each cycle.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Aged between 18 and 75 (inclusive);
• For patients with DLBCL confirmed by histopathology (which needs to be confirmed by specimens after this or past recurrence), the following DLBCL histology will be considered eligible for study enrollment:

DLBCL, NOS(includes GCB type and ABC type); T-cell rich large B-cell lymphoma; High-grade B-cell lymphoma with MYC and BCL-2 and/or BCL-6 rearrangement; High-grade B-cell lymphoma, NOS; Primary mediastinal (thymus) large B-cell lymphoma; EB virus positive DLBCL, NOS;HHV-8 positive DLBCL, NOS;

• Relapsed refractory patients, defined as those who had no response after first-line treatment (including immunochemotherapy, chemotherapy or hematopoietic stem cell transplantation) or relapsed or refractory after remission;
• There is at least one two-dimensional measurable lesion with a short diameter ≥1.0cm;
• Estimated survival time ≥3 months;
• The patient is informed and agrees to the program;
• ECOG score 0-2 points;
• Those who understand the procedure and content of the experiment, voluntarily participate in the study and sign the informed consent;
• Patients can follow up on schedule, communicate well with researchers and complete the trial according to the trial regulations;
• Confirm negative pregnancy test of female patients of childbearing age within 7 days before administration; Women and men in the reproductive period must agree to use medically recognized effective contraception throughout the treatment period and for 6 months after the end of the trial.

Exclusion Criteria

• Active bleeding within 4 weeks prior to initial administration or anticoagulant therapy such as warfarin or vitamin K antagonists during the study period, or a tendency to bleed (such as esophageal varicose veins at risk of bleeding, locally active ulcerative lesions) or a clotting disorder deemed by the investigator;
• History of stroke and intracranial hemorrhage within 6 months before the first administration, except intracranial hemorrhage after surgery;
• Those who cannot stop or adjust moderate or strong CYP3A inhibitors;
• Have received organ transplantation or allogeneic stem cell transplantation;
• Previous or concurrent history of other malignant tumors;
• Chronic or currently active infectious diseases requiring systemic antibiotic, antifungal, or antiviral treatment (except EBV infections);
• Accompanied by uncontrolled cardiovascular and cerebrovascular diseases, thrombotic diseases, connective tissue diseases and other diseases. Those who were not considered suitable for inclusion by the researchers;
• Laboratory test value at screening (unless due to lymphoma) : Leukocyte count < 3.5×109/L, neutrophils <1.5×109/L, platelets <80×109/L, hemoglobin <100g/L, ALT or AST were 2.5 times higher than the upper limit of normal, bilirubin was 1.5 times higher than the upper limit of normal, creatinine level was 1.5 times higher than the upper limit of normal;
• HbsAg positive patients need to check HBV-DNA < 104 to be enrolled. In addition, if HBsAg is negative but HBcAb is positive (regardless of HBsAb status), HBV-DNA testing is also required, and HBV-DNA results < 104 are required to be enrolled and continue treatment and monitoring of HBV-DNA. Patients with HCV antibody positive were required to check HCV-RNA quantitative DNA < 103 to be enrolled;
• HIV antibody, treponema pallidum antibody positive;
• Pregnant or lactating women;
• Those who have a history of drug use or drug abuse upon inquiry;
• Patient communication, understanding and cooperation are not enough, or compliance is poor, and it cannot be guaranteed that the program is carried out according to the requirements;
• Known allergy to the investigational drug or its related ingredients;
• Patients with past or current lymphoma central invasion;
• The patient is unable to swallow the capsule or has a disease or condition that severely affects gastrointestinal function, such as malabsorption syndrome, removal of the stomach or small intestine, or complete intestinal obstruction;
• Patients who could not stop using any other antitumor drugs within 2 weeks prior to medication in this study;
• Participants considered unsuitable for this clinical trial due to various other reasons.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

2nd Affiliated Hospital, School of Medicine, Zhejiang University

Hanzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xianggui Yuan

Role: CONTACT

yuanxg@zju.edu.cn

+8613989883884

Wenbin Qian

Role: CONTACT

qianwb@zju.edu.cn

+8613605801032

Facility Contacts

Wenbin Qian

Role: primary

qianwb@zju.edu.cn

+8613605801032

Other Identifiers

R2024279

Identifier Type: -

Identifier Source: org_study_id