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

Primary Purpose

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

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Rituximab

Zanubrutinib

Cyclophosphamide

Epirubicin

Vincristine

Prednisone

About this trial

This is an interventional treatment trial for Diffuse Large B Cell Lymphoma focused on measuring Diffuse Large B Cell Lymphoma, Zanubrutinib, CD79A/CD79B, Genetic Abnormality

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age between 18 to 70 years old (including 18 and 70)
Diagnosed as diffuse large B cell lymphoma
CD79A/CD79B genetic abnormality
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%)
Having at least one measurable lesions
World health organization-Eastern Cooperative Oncology Group Performance Status (ECOG) 0-1
Life expectancy no less than 3 months
enough main organ function
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
Agreeing to sign the written informed consents

Exclusion Criteria:

Diagnosed as high-grade B-cell lymphoma, including non-specified and double-strike or triple-strike
Diagnosed as grey-zone lymphoma
Diagnosed as primary mediastinal large B-cell lymphoma
Diagnosed as CD20 negative diffuse large B-cell lymphoma
Active malignant tumor need be treated at the same time
Other malignant tumor history
Serious surgery and trauma less than two weeks
Systemic therapy for serious acute/chronic infection
Congestive heart failure, uncontrolled coronary heart disease, arrhythmia and heart infarction less than 6 months
Vaccination with live attenuated vaccine less than 4 weeks
HIV-positive, AIDS patients and untreated active hepatitis
Patients with a history of deep vein thrombosis or pulmonary embolism less than 12 months
Patients with a history of mental illness
Researchers determine unsuited to participate in this trial

Sites / Locations

Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou universityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Zanubrutinib Combined With Standard Chemotherapy

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

objective response rate

the total proportion of patients with complete response (CR) and partial response (PR)

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

2-year overall survival

from date of first day of treatment to the date of death by any cause

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)

Full Information

NCT ID

NCT04668365

First Posted

December 8, 2020

Last Updated

May 17, 2023

Sponsor

Henan Cancer Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04668365

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

December 25, 2020 (Actual)

Primary Completion Date

December 25, 2023 (Anticipated)

Study Completion Date

December 25, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Henan Cancer Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

Diffuse Large B Cell Lymphoma, Zanubrutinib, CD79A/CD79B, Genetic Abnormality

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

59 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Zanubrutinib Combined With Standard Chemotherapy

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Rituximab

Other Intervention Name(s)

RiTUXimab Injection

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Zanubrutinib

Other Intervention Name(s)

Zanubrutinib Pill

Intervention Description

160mg twice daily continuous oral administration.

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

Cyclophosphamide Injection

Intervention Description

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

Intervention Name(s)

Epirubicin

Other Intervention Name(s)

Epirubicin Injection

Intervention Description

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

Intervention Name(s)

Vincristine

Other Intervention Name(s)

Vincristine Injection

Intervention Description

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

Intervention Name(s)

Prednisone

Other Intervention Name(s)

Prednisone Pill

Intervention Description

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.

Primary Outcome Measure Information:

Title

Proportion of complete remission for 3-4 weeks after induction treatment

Description

the total proportion of patients with complete remission (CR) for 3-4 weeks after induction treatment

Time Frame

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 Outcome Measure Information:

Title

objective response rate

Description

the total proportion of patients with complete response (CR) and partial response (PR)

Time Frame

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)

Title

2-year progression-free survival

Description

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

Time Frame

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)

Title

2-year overall survival

Description

from date of first day of treatment to the date of death by any cause

Time Frame

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)

Title

incidence and relationship with study drugs of grade 3-4 adverse events

Description

the incidence and relationship with study drugs of grade 3 or 4 adverse events (based on NCI CTC-AE v4.03)

Time Frame

from the date of the first cycle of treatment to 18 months after last patient's enrollment (each cycle is 21 days)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age between 18 to 70 years old (including 18 and 70) Diagnosed as diffuse large B cell lymphoma CD79A/CD79B genetic abnormality 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%) Having at least one measurable lesions World health organization-Eastern Cooperative Oncology Group Performance Status (ECOG) 0-1 Life expectancy no less than 3 months enough main organ function 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 Agreeing to sign the written informed consents Exclusion Criteria: Diagnosed as high-grade B-cell lymphoma, including non-specified and double-strike or triple-strike Diagnosed as grey-zone lymphoma Diagnosed as primary mediastinal large B-cell lymphoma Diagnosed as CD20 negative diffuse large B-cell lymphoma Active malignant tumor need be treated at the same time Other malignant tumor history Serious surgery and trauma less than two weeks Systemic therapy for serious acute/chronic infection Congestive heart failure, uncontrolled coronary heart disease, arrhythmia and heart infarction less than 6 months Vaccination with live attenuated vaccine less than 4 weeks HIV-positive, AIDS patients and untreated active hepatitis Patients with a history of deep vein thrombosis or pulmonary embolism less than 12 months Patients with a history of mental illness Researchers determine unsuited to participate in this trial

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Zhihua Yao, M.D. Ph.D

Phone

+8613592622292

zlyyyaozhihua1260@zzu.edu.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Yanyan Liu, M.D. Ph.D

Phone

+8613838176375

yyliu@zzu.edu.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Zhihua Yao, M.D. Ph.D

Organizational Affiliation

Henan Cancer Hospital

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Yanyan Liu, M.D. Ph.D

Organizational Affiliation

Henan Cancer Hospital

Official's Role

Study Director

Facility Information:

Facility Name

Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university

City

Zhengzhou

State/Province

Henan

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Zhihua Yao, M.D. Ph.D

Phone

+8613592622292

zlyyyaozhihua1260@zzu.edu.cn

First Name & Middle Initial & Last Name & Degree

Zhihua Yao, M.D. Ph.D

12. IPD Sharing Statement

Learn more about this trial

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

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