Zanubrutinib Combined With Standard Chemotherapy in the Treatment for Patients With Diffuse Large B Cell Lymphoma

NCT ID: NCT04668365

Last Updated: 2025-04-25

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE2
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-25
• Study Completion Date: 2025-12-25

Brief Summary

This is a prospective single arm, multi-center, phase II clinical trial to observe the efficacy and safety of zanubrutinib combined with standard chemotherapy in the treatment for patients with diffuse large B cell lymphoma and CD79A/CD79B genetic abnormality.

Detailed Description

Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma (NHL). Currently, R-CHOP is world-widely used in the first-line treatment for DLBCL. There are about one second of patients suffering relapse and drug resistance. ABC-DLBCL mainly relies on the chronical activity of BCR signal, which can activate the downstream NF-kB pathway through BTK and MYD88, thereby promoting the occurrence of tumors. A study by Wyndham H Wilson et al. showed that 23% of ABC-DLBCL patients were accompanied by acquired functional mutations of the BCR component CD79A/CD79B. Zanubrutinib is a new BTK inhibitor. The goal of our trial is to assess the efficacy and safety of zanubrutinib combined with standard chemotherapy in the treatment for patients with diffuse large B cell lymphoma and CD79A/CD79B genetic abnormality.

Conditions

Diffuse Large B Cell Lymphoma; CD79A Gene Mutation; CD79B Gene Mutation

Study Design

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

Study Groups

Zanubrutinib Combined With Standard Chemotherapy

A: For the first-line treatment:

Rituximab, 375mg/m2, Intravenous administration on day 0, combined with regimen：CHOP (Cyclophosphamide, Epirubicin, Vincristine and Prednisone): repeated every 3 weeks, up to 6 cycles.

Zanubrutinib, 160mg twice daily continuous oral administration from 2 to 6 cycles for patients with CD79A/CD79B genetic abnormality.

Zanubrutinib combined with Rituximab for the 7 cycle.

B: For R/R DBCLC:

Rituximab, 375mg/m2, Intravenous administration on day 0, combined with regimen: GemOx(Gemcitabine, Oxaliplatin)/ DHAP(Cisplatin, Cytarabine, Dexamethasone)/ ICE(Ifosfamide, Etoposide, Carboplatin)/ GDP(Gemcitabine, Cisplatin, Dexamethasone): repeated every 3 weeks, up to 5 cycles.

Zanubrutinib, 160mg twice daily continuous oral administration from 2 to 5 cycles for patients with CD79A/CD79B genetic abnormality.

Maintenance treatment: Zanubrutinib, 160mg twice daily continuous oral administration for 12 months.

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

375mg/m2, Intravenous administration on day 0 of each 3-week cycle.

Zanubrutinib

Intervention Type: DRUG

160mg twice daily continuous oral administration.

Cyclophosphamide

Intervention Type: DRUG

750mg/m2, Intravenous administration on day 1 of each 3-week cycle until disease progression/stable disease after 2 cycles treatment, disease progression after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.

Epirubicin

Intervention Type: DRUG

70mg/m2, Intravenous administration on day 1 of each 3-week cycle until disease progression/stable disease after 2 cycles treatment, disease progression after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.

Vincristine

Intervention Type: DRUG

1.4mg/m2 (Max: 2mg), Intravenous administration on day 1 of each 3-week cycle until disease progression/stable disease after 2 cycles treatment, disease progression after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.

Prednisone

Intervention Type: DRUG

100mg, oral administration on day 1 to 5 of each 3-week cycle until disease progression/stable disease after 2 cycles treatment, disease progression after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.

Interventions

Rituximab

375mg/m2, Intravenous administration on day 0 of each 3-week cycle.

Intervention Type: DRUG

Zanubrutinib

160mg twice daily continuous oral administration.

Intervention Type: DRUG

Cyclophosphamide

750mg/m2, Intravenous administration on day 1 of each 3-week cycle until disease progression/stable disease after 2 cycles treatment, disease progression after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.

Intervention Type: DRUG

Epirubicin

70mg/m2, Intravenous administration on day 1 of each 3-week cycle until disease progression/stable disease after 2 cycles treatment, disease progression after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.

Intervention Type: DRUG

Vincristine

1.4mg/m2 (Max: 2mg), Intravenous administration on day 1 of each 3-week cycle until disease progression/stable disease after 2 cycles treatment, disease progression after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.

Intervention Type: DRUG

Prednisone

100mg, oral administration on day 1 to 5 of each 3-week cycle until disease progression/stable disease after 2 cycles treatment, disease progression after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.

Intervention Type: DRUG

Other Intervention Names

RiTUXimab Injection; Zanubrutinib Pill; Cyclophosphamide Injection; Epirubicin Injection; Vincristine Injection; Prednisone Pill

Eligibility Criteria

Inclusion Criteria

1. Age between 18 to 75 years old (including 18 and 75)

2. Diagnosed as diffuse large B cell lymphoma

3. CD79A/CD79B genetic abnormality

4. Subjects with untreated or relapsed/refractory DLBCL

5. Having at least one measurable lesions

6. World health organization-Eastern Cooperative Oncology Group Performance Status (ECOG) 0-1

7. Life expectancy no less than 3 months

8. enough main organ function

9. Pregnancy test within 7 days must be negative for women of childbearing period, and appropriate measures should be taken for contraception for women in childbearing period during the study and six months after this study

10. Agreeing to sign the written informed consents

Exclusion Criteria

1. Diagnosed as high-grade B-cell lymphoma, including non-specified and double-strike or triple-strike

2. Diagnosed as grey-zone lymphoma

3. Diagnosed as primary mediastinal large B-cell lymphoma

4. Diagnosed as CD20 negative diffuse large B-cell lymphoma

5. Active malignant tumor need be treated at the same time

6. Other malignant tumor history

7. Serious surgery and trauma less than two weeks

8. Systemic therapy for serious acute/chronic infection

9. Congestive heart failure, uncontrolled coronary heart disease, arrhythmia and heart infarction less than 6 months

10. Vaccination with live attenuated vaccine less than 4 weeks

11. HIV-positive, AIDS patients and untreated active hepatitis

12. Patients with a history of deep vein thrombosis or pulmonary embolism less than 12 months

13. Patients with a history of mental illness

14. Researchers determine unsuited to participate in this trial

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

Sponsors

Henan Cancer Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Zhihua Yao, PhD

Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhihua Yao, M.D. Ph.D

Role: STUDY_DIRECTOR

Henan Cancer Hospital

Yanyan Liu, M.D. Ph.D

Role: STUDY_DIRECTOR

Henan Cancer Hospital

Locations

Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university

Zhengzhou, Henan, China

Countries

China

Other Identifiers

HNSZLYYNHL05

Identifier Type: -

Identifier Source: org_study_id