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
试验速览
- 阶段
- 2 期
- 状态
- 暂停
- 入组人数
- 59
- 试验地点
- 1
- 主要终点
- Proportion of complete remission for 3-4 weeks after induction treatment
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 18 to 75 years old (including 18 and 75)
- •Diagnosed as diffuse large B cell lymphoma
- •CD79A/CD79B genetic abnormality
- •Subjects with untreated or relapsed/refractory DLBCL
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Rituximab (Drug)
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.
干预措施: Zanubrutinib (Drug)
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.
干预措施: Cyclophosphamide (Drug)
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.
干预措施: Epirubicin (Drug)
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.
干预措施: Vincristine (Drug)
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.
干预措施: Prednisone (Drug)
结局指标
主要结局
Proportion of complete remission for 3-4 weeks after induction treatment
时间窗: 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)
the total proportion of patients with complete remission (CR) for 3-4 weeks after induction treatment
次要结局
- objective response rate(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))
- 2-year progression-free survival(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))
- 2-year overall survival(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))
- incidence and relationship with study drugs of grade 3-4 adverse events(from the date of the first cycle of treatment to 18 months after last patient's enrollment (each cycle is 21 days))
研究者
Zhihua Yao, PhD
Director
Henan Cancer Hospital