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

Diffuse Large B Cell Lymphoma Clinical Trial

Official title:

A Single Arm, Multi-center, Phase II Clinical Trial of Zanubrutinib Combined With Standard Chemotherapy in the Treatment for Patients With Diffuse Large B Cell Lymphoma and CD79A/CD79B Genetic Abnormality

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04668365
• Other study ID #: HNSZLYYNHL05
• Status: Recruiting
• Phase: Phase 2
• Start date: December 25, 2020
• Est. completion date: December 25, 2025

Study information

• Verified date: May 2023
• Source: Henan Cancer Hospital
• Contact: Zhihua Yao, M.D. Ph.D
• Phone: +8613592622292
• Email: zlyyyaozhihua1260[@]zzu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 59
• Est. completion date: December 25, 2025
• Est. primary completion date: December 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Age between 18 to 70 years old (including 18 and 70)

2. Diagnosed as diffuse large B cell lymphoma

3. CD79A/CD79B genetic abnormality

4. Subjects must be untreated or R/R and either a or b (a: medium to high risk/high risk:

International Prognostic Index (IPI) score 3-5, aaIPI score 2-3 or NCCN-IPI score= 4/ b: Immunohistochemical staining of double expression (BCL2 = 70% and C-MYC = 40%) or P53 protein mutation positive = 50%)

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

Related Conditions & MeSH terms

• CD79A Gene Mutation
• CD79B Gene Mutation
• Diffuse Large B Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Rituximab
375mg/m2, Intravenous administration on day 0 of each 3-week cycle.
• Zanubrutinib
160mg twice daily continuous oral administration.
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
China	Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Henan Cancer Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of complete remission for 3-4 weeks after induction treatment	the total proportion of patients with complete remission (CR) for 3-4 weeks after induction treatment	from the date of the first cycle of treatment to 3-4 weeks after induction treatment of the last included patient (each cycle is 21 days)
Secondary	objective response rate	the total proportion of patients with complete response (CR) and partial response (PR)	every 6 weeks from the day of the first cycle of induction chemotherapy treatment and every 8 weeks from the day of the first cycle of maintenance treatment to 18 months after last patient's enrollment (each cycle is 21 days)
Secondary	2-year progression-free survival	the total proportion of patients with no progression from date of the first day of treatment to the date of confirmed progressive disease or death which one occurs first	from the day of the first cycle of treatment to the date of confirmed progressive disease or death, whichever occurs first, up to 2 years after last patient's enrollment (each cycle is 21 days)
Secondary	2-year overall survival	from date of first day of treatment to the date of death by any cause	from date of the first cycle of treatment to the date of death from any cause, assessed up to 2 years (each cycle is 21 days)
Secondary	incidence and relationship with study drugs of grade 3-4 adverse events	the incidence and relationship with study drugs of grade 3 or 4 adverse events (based on NCI CTC-AE v4.03)	from the date of the first cycle of treatment to 18 months after last patient's enrollment (each cycle is 21 days)