A Study to Evaluate Efficacy and Safety of Zanubrutinib With R-CHOP in Newly Diagnosed Non-GCB DLBCL Patients With Double Expression

NCT05189197 | Active Not Recruiting Phase 2

• 1 other identifier: ZRCHOP-BGB-3111-2004-IIT
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

Zanubrutinib is a highly specific, potent new Bruton's tyrosine kinase （BTK） inhibitor, with minimal off-target inhibition of other kinases. This is a single-arm, open-label Phase II study to evaluate the efficacy and safety of zanubrutinib in combination with Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in newly diagnosed non-GCB Diffuse large B-cell lymphoma (DLBCL) patients with co-expression of B-cell lymphoma 2 （BCL2）and myelocytomatosis oncogene（MYC）.

Conditions

Diffuse Large B-cell Lymphoma(DLBCL)

Keywords

Diffuse large B-cell lymphoma; Zanubrutinib

Outcome Measures

Primary Outcomes (1)

• 3-year event-free survival (EFS) rate

  3-year EFS rate is defined as the proportion of patients free from EFS events at 3 years after the initiation of zanubrutinib and RCHOP combination therapy estimated using the Kaplan-Meier method. EFS is defined as the duration from the initiation of zanubrutinib and RCHOP combination therapy to the date of documented disease progression, relapse from CR, initiation of subsequent systemic anti-lymphoma therapy for either positron emission computed tomography (PET)-positive or biopsy-proven residual disease after six cycles of Zanubrutinib and R-CHOP combination therapy, or any-cause death whichever occurs first.

  up to 3 years

Secondary Outcomes (5)

• Overall response rate (ORR)

  up to 18 weeks

• Complete response rate (CRR)

  up to 18 weeks

• 3-year progression-free survival rate （PFS)

  up to 3 years

• 3-year overall survival (OS) rate

  up to 3 years

• adverse event（AE）

  up to 2 years

Study Arms (1)

Experimental: Zanubrutinib + R-CHOP

EXPERIMENTAL

Zanubrutinib 160 mg bis in die（BID） administered by oral every day of each 21-day cycle. Rituximab 375 mg/m2, Cyclophosphamide 750 mg/m2, Doxorubicin 50 mg/m2 and Vincristine 1.4 mg/m2 (maximum total 2 mg) administered by IV infusion on Day 1 of each 21-day cycle. Prednisone 100 mg administered by oral on Day 1-5 of each 21-day cycle. After 6 cycles of zanubrutinib and R-CHOP combination therapy, patients achieved complete response （CR）will continue to receive zanubrutinib 160mg BID for 1 year.

Drug: Zanubrutinib + R-CHOP

Interventions

Zanubrutinib + R-CHOP DRUG

Zanubrutinib 160 mg BID administered by oral every day of each 21-day cycle. Rituximab 375 mg/m2, Cyclophosphamide 750 mg/m2, Doxorubicin 50 mg/m2 and Vincristine 1.4 mg/m2 (maximum total 2 mg) administered by IV infusion on Day 1 of each 21-day cycle. Prednisone 100 mg administered by oral on Day 1-5 of each 21-day cycle. After 6 cycles of zanubrutinib and R-CHOP combination therapy, patients achieved CR will continue to receive zanubrutinib 160mg BID for 1 year.

Also known as: Brukinsa+Mabthera +CHOP

Experimental: Zanubrutinib + R-CHOP

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must be 18 years of age or older.
• No prior treatment for DLBCL.
• Histologically - confirmed non-GCB subtype.
• MYC+≥40% and BCL2+≥50% by IHC
• Lesions must be measurable. A measurable node lesion must have a longest diameter greater than 1.5 cm. A measurable extra-nodal lesion should have a longest diameter greater than 1.0 cm.
• Eastern Cooperative Oncology Group performance status grade of 0, 1, or 2
• Stage II (not candidates for local X-ray therapy), III, or IV disease by the Ann Arbor Classification
• Hematology values must be within the following limits at baseline:
• Neutrophils ≥ 1 x 109/L, independent of growth factor support within 7 days of initiation of the combination therapy.
• Platelets ≥ 75x 109/L, independent of growth factor support or transfusion within 7 days of initiation of the combination therapy. (platelets≥ 50 x 109/L, if there is bone marrow involvement.)
• Biochemical values must be within the following limits at baseline:
• Alanine aminotransferase (ALT) ≤3 x upper limit of normal (ULN). Aspartate aminotransferase (AST) ≤3 x ULN.
• Total bilirubin ≤1.5 x ULN, unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin.
• Serum creatinine ≤2 x ULN or estimated Glomerular Filtration Rate≥40 mL/min/1.73m2
• International normalized ratio (INR) ≤1.5 and activated partial thromboplastin time (APTT) ≤1.5 x ULN.

You may not qualify if:

• Primary mediastinal lymphoma.
• Central nervous system involvement lymphoma.
• Histologically transformed lymphoma.
• Diagnosed or treated for malignancies other than DLBCL.
• History of stroke or intracranial hemorrhage within 6 months.
• Major surgery within 4 weeks.
• Required ongoing treatment with medication that are strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or strong/median effect CYP3A inducers.
• Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification, or Echocardiography: Left ventricular ejection fraction (LVEF) \< 50%
• Active, clinically significant Electrocardiogram (ECG) abnormalities including second degree atrioventricular (AV) block Type II, or third-degree AV block or QT interval corrected for heart rate (QTcF) prolongation, defined as a QTcF \> 450 msec.
• Any uncontrolled active systemic infection requiring intravenous (IV) antibiotics.
• Known human immunodeficiency virus (HIV) infection, or active hepatitis B or hepatitis C infection.
• Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of zanubrutinib capsules, or put the study outcomes at undue risk.
• Pregnant or lactating women.

Sponsors & Collaborators

• Fudan University: lead
• Baotou Cancer Hospital: collaborator
• Xiangya Hospital of Central South University: collaborator
• Shanghai Changzheng Hospital: collaborator

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, China

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

zanubrutinib

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Junning Cao

  Fudan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of department

Study Record Dates

• First Submitted: December 29, 2021
• First Posted: January 12, 2022
• Study Start: January 18, 2022
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2026
• Last Updated: May 17, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)