Zanubrutinib Combined With Standard Chemotherapy in the Treatment for Patients With Diffuse Large B Cell Lymphoma
Phase 2
Suspended
- Conditions
- Diffuse Large B Cell LymphomaCD79B Gene MutationCD79A Gene Mutation
- Interventions
- Registration Number
- NCT04668365
- Lead Sponsor
- Henan Cancer Hospital
- 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.
Recruitment & Eligibility
- Status
- SUSPENDED
- Sex
- All
- Target Recruitment
- 59
Inclusion Criteria
- 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
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Zanubrutinib Combined With Standard Chemotherapy Rituximab 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. Zanubrutinib Combined With Standard Chemotherapy Zanubrutinib 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. Zanubrutinib Combined With Standard Chemotherapy Cyclophosphamide 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. Zanubrutinib Combined With Standard Chemotherapy Epirubicin 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. Zanubrutinib Combined With Standard Chemotherapy Prednisone 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. Zanubrutinib Combined With Standard Chemotherapy Vincristine 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.
- Primary Outcome Measures
Name Time Method Proportion of complete remission 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) the total proportion of patients with complete remission (CR) for 3-4 weeks after induction treatment
- Secondary Outcome Measures
Name Time Method 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) the total proportion of patients with complete response (CR) and partial response (PR)
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) 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 the first cycle of treatment to the date of death from any cause, assessed up to 2 years (each cycle is 21 days) 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 from the date of the first cycle of treatment to 18 months after last patient's enrollment (each cycle is 21 days) the incidence and relationship with study drugs of grade 3 or 4 adverse events (based on NCI CTC-AE v4.03)
Trial Locations
- Locations (1)
Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university
🇨🇳Zhengzhou, Henan, China