Clinical trial NCT04668365: 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
Overall status: SUSPENDED
Phase: PHASE2
Conditions: Diffuse Large B Cell Lymphoma
CD79A Gene Mutation
CD79B Gene Mutation
Keywords: Diffuse Large B Cell Lymphoma
Zanubrutinib
CD79A/CD79B
Genetic Abnormality
Lead sponsor: Henan Cancer Hospital
Sponsor class: OTHER_GOV
First posted: 2020-12-16
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Proportion of complete remission for 3-4 weeks after induction treatment
timeFrame: 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 outcomes:
measure: objective response rate
timeFrame: 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)
measure: 2-year progression-free survival
timeFrame: 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)
measure: 2-year overall survival
timeFrame: 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)
measure: incidence and relationship with study drugs of grade 3-4 adverse events
timeFrame: from the date of the first cycle of treatment to 18 months after last patient's enrollment (each cycle is 21 days)
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university
state: Henan
Study officials:
affiliation: Henan Cancer Hospital
name: Zhihua Yao, M.D. Ph.D
role: STUDY_DIRECTOR
affiliation: Henan Cancer Hospital
name: Yanyan Liu, M.D. Ph.D
role: STUDY_DIRECTOR
References: