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

• ClinicalTrials.gov Identifier: NCT04668365
• Recruitment Status: Recruiting
• First Posted: December 16, 2020
• Last Update Posted: January 25, 2022
• Sponsor: Henan Cancer Hospital
• Information provided by (Responsible Party): yaozhihua, Henan Cancer Hospital

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.

Condition or disease	Intervention/treatment	Phase
Diffuse Large B Cell Lymphoma; CD79A Gene Mutation; CD79B Gene Mutation	Drug: Rituximab; Drug: Zanubrutinib; Drug: Cyclophosphamide; Drug: Epirubicin; Drug: Vincristine; Drug: Prednisone	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 59 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: December 25, 2020
• Estimated Primary Completion Date: December 25, 2023
• Estimated Study Completion Date: December 25, 2025

Arms and Interventions

Arm

Intervention/treatment

Experimental: 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.

Drug: Rituximab; 375mg/m2, Intravenous administration on day 0 of each 3-week cycle.; Other Name: RiTUXimab Injection; Drug: Zanubrutinib; 160mg twice daily continuous oral administration.; Other Name: Zanubrutinib Pill; Drug: 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.; Other Name: Cyclophosphamide Injection; Drug: 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.; Other Name: Epirubicin Injection; Drug: 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.; Other Name: Vincristine Injection; Drug: 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.; Other Name: Prednisone Pill

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. objective response rate [ 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) ]
   the total proportion of patients with complete response (CR) and partial response (PR)
2. 2-year progression-free survival [ 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) ]
   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
3. 2-year overall survival [ 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) ]
   from date of first day of treatment to the date of death by any cause
4. incidence and relationship with study drugs of grade 3-4 adverse events [ Time Frame: 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)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Zhihua Yao, M.D. Ph.D; +8613592622292; zlyyyaozhihua1260@zzu.edu.cn

Contact: Yanyan Liu, M.D. Ph.D; +8613838176375; yyliu@zzu.edu.cn

Locations

China, Henan

Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university; Recruiting

Zhengzhou, Henan, China

Contact: Zhihua Yao, M.D. Ph.D +8613592622292 zlyyyaozhihua1260@zzu.edu.cn

Principal Investigator: Zhihua Yao, M.D. Ph.D

Sponsors and Collaborators

Henan Cancer Hospital

Investigators

• Study Director: Zhihua Yao, M.D. Ph.D; Henan Cancer Hospital
• Study Director: Yanyan Liu, M.D. Ph.D; Henan Cancer Hospital

More Information

• Responsible Party: yaozhihua, Director, Henan Cancer Hospital
• ClinicalTrials.gov Identifier: NCT04668365
• Other Study ID Numbers: HNSZLYYNHL05
• First Posted: December 16, 2020
• Last Update Posted: January 25, 2022
• Last Verified: January 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by yaozhihua, Henan Cancer Hospital:

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

Additional relevant MeSH terms:

Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Prednisone; Cyclophosphamide; Rituximab; Vincristine; Epirubicin; Zanubrutinib; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists