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

Sponsor
Henan Cancer Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT04668365
Collaborator
(none)
59
1
1
60
1

Study Details

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.

Study Design

Study Type:
Interventional
Anticipated 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 :
Dec 25, 2020
Anticipated Primary Completion Date :
Dec 25, 2023
Anticipated Study Completion Date :
Dec 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 Names:
  • RiTUXimab Injection
  • Drug: Zanubrutinib
    160mg twice daily continuous oral administration.
    Other Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • Prednisone Pill
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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. 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

    3. 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

    4. 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)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Locations

    Site City State Country Postal Code
    1 Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university Zhengzhou Henan China

    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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    yaozhihua, Director, Henan Cancer Hospital
    ClinicalTrials.gov Identifier:
    NCT04668365
    Other Study ID Numbers:
    • HNSZLYYNHL05
    First Posted:
    Dec 16, 2020
    Last Update Posted:
    Jan 25, 2022
    Last Verified:
    Jan 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by yaozhihua, Director, Henan Cancer Hospital
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jan 25, 2022