Zanubrutinib Combined With R-CHOP Regimen in the Treatment of Newly Diagnosed DLBCL With High-risk Factors

A Single-arm, Prospective Clinical Study on the Antitumor Activity and Safety of Zanubrutinib Combined With R-CHOP Regimen in the Treatment of Newly Diagnosed DLBCL With High-risk Factors

This study is a prospective, open-label, single-arm phase II clinical study to evaluate the safety and efficacy of zanubrutinib plus R-CHOP (ZR-CHOP) as the first-line therapy for newly diagnosed diffuse large B-cell lymphoma patients with high-risk factors.

Study Overview

• Status: Not yet recruiting
• Conditions: Diffuse Large B Cell Lymphoma
• Intervention / Treatment: Drug: Zanubrutinib; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Epirubicin; Drug: Vincristine; Drug: Prednisone

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaojing Xing, Ph.D; Phone Number: 18900917660; Email: 13940066477@163.com

Study Locations

• China
  • Liaoning
    • Shenyang, Liaoning, China, 110000
      • Xing Xiaojing

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed DLBCL patients have one of the following risk factors(including but not limited to double expression, extranodal involvement, high ki67, bulky)；
2. Age ≥ 18 years old;
3. At least one measurable lesion (defined as lymph node lesion ≥15mm, extra-segmental lesions ≥ 10mm);
4. ECOG performance status 0-2;
5. Functions of major organs meet the following conditions: Echocardiography left ventricular ejection fraction ≥50%; Creatinine clearance ≥30 ml/min; ALT and AST≤3 times the normal range；
6. Hematopoietic function should meet the following conditions: Platelet count ≥50×109/L; Hemoglobin ≥ 8.0g /dL; Absolute count of neutrophil (ANC)≥1.0×109/L;
7. Expected survival of ≧3 months

Exclusion Criteria:

1. Major surgery within 4 weeks before treatment;
2. Severe organ dysfunction(including but not limited to complications of uncontrolled cardiovascular diseases, blood clotting disorders, connective tissue diseases, serious infectious diseases and other diseases);
3. Patients who cannot cooperate with treatment or follow-up on time.
4. Pregnant or lactating females;
5. any uncontrolled active systemic infection requiring intravenous (IV) antibiotics;
6. There was a history of other active malignant diseases within the 2 years prior to study entry, except for: (1) adequately treated cervical carcinoma in situ; (2) local skin basal cell carcinoma or squamous cell carcinoma; (3) previous malignant disease that is under control and has undergone local radical treatment (surgical or other forms).
7. History of severe hemorrhagic disorders, such as hemophilia A, hemophilia B, von Willebrand's disease, or spontaneous bleeding requiring blood transfusion or other medical intervention
8. Human immunodeficiency virus (HIV) infection or the following serological status reflecting the presence of active hepatitis B or C virus infection: a. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) are present. Patients who are HBCAB-positive, HBsAg negative, have no hepatitis b virus (HBV) DNA (< 20 IU/mL), and agree to be monitored for HBV virus reactivation can be enrolled. Antibodies to the hepatitis C virus (HCV) are present. HCV antibody-positive patients with no HCV RNA detected could be included in the group.
9. The presence of any life-threatening disease, medical condition, or organ system dysfunction that the investigator believes may affect the subject's safety or pose a risk to the study.
10. The researchers think it is not suitable to participate in this experiment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Zanubrutinib + R-CHOP

Drug: Zanubrutinib; Zanubrutinib 160mg bid p.o d0-d20(21-day cycles); Drug: Rituximab; Rituximab 375 mg/m2 i.v d0(21-day cycles); Drug: Cyclophosphamide; Cyclophosphamide 750 mg/m2 i.v d1(21-day cycles); Drug: Epirubicin; Epirubicin 75 mg/m2 i.v d1 or liposome adriamycin 35mg/m2 i.v d1(21-day cycles); Drug: Vincristine; Vincristine 1.4 mg/m2 i.v d1 (2 mg max) (21-day cycles); Drug: Prednisone; Prednisone 100 mg p.o d1-d5 (21-day cycles)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Complete response rate（CRR）	Up to approximately 2.5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall response rate （ORR）	Up to approximately 2.5 years
Progression-free Survival(PFS)	Up to approximately 2.5 years
Overall survival (OS)	Up to approximately 2.5 years
Duration of Response	At 2 years
Incidence of adverse event	At 2 years
Assessment of the correlation between MYD88、CD79B、NOTCH1、BCL6、NOTCH2 or other gene abnormality and efficacy.	At 2 years

Collaborators and Investigators

• Sponsor: Liaoning Tumor Hospital & Institute
• Investigators: Principal Investigator: Xiaojing Xing, Ph.D, Liaoning Tumor Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2023
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: March 20, 2023
• First Submitted That Met QC Criteria: June 1, 2023
• First Posted (Actual): June 5, 2023

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 26, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Antibiotics, Antineoplastic; Cyclophosphamide; Epirubicin; Rituximab; Prednisone; Vincristine; Zanubrutinib
• Other Study ID Numbers: ZR-CHOP HR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No