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Zanubrutinib Combined With R-CHOP in the Treatment of Newly Diagnosed DLBCL With p53 Protein Expression

Primary Purpose

Diffuse Large B Cell Lymphoma

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Zanubrutinib plus RCHOP
Sponsored by
Huazhong University of Science and Technology
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B Cell Lymphoma focused on measuring DLBCL, Diffuse Large b-cell lymphoma, p53, zanubrutinib

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age ≥18 years, ≤ 75 years, both sexes; Diff use large B-cell lymphoma diagnosed by histopathology without previous systemic DLBCL treatment; ECOG score: 0-2; Predicted survival ≥3 months; Patients with positive p53 expression detected by immunohistochemistry (≥50% ); The patients had certain conditions of organ function reserve, and the laboratory tests within 1 week before enrollment met the following conditions: Blood routine: neutrophil count (NEUT) ≥1.5×10^9/L, platelet count (PLT) ≥75×10^9/L, hemoglobin (HGB) ≥80 g/L; G-CSF was not used in the past 7 days (the researchers judged that the lymphoma-induced cytopenia could be included). Liver function: Total bilirubin (TBIL) ≤1.5× upper limit of the normal range (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN; If liver metastases were present, TBIL≤3×ULN, ALT and AST≤5×ULN; Renal function: serum creatinine (Cr) ≤2.0×ULN or creatinine clearance (CCr) ≥60ml/min; Cardiac function: LVEF≥50%, ECG did not indicate any acute myocardial infarction, arrhythmia, or atrioventricular conduction block above grade I; Thyroid function: thyroid stimulating hormone (TSH) was within the normal range. If TSH is abnormal, free triiodothyronine (FT3) and free thyroxine (FT4) should be within the normal range or abnormal without clinical significance. According to the Lugano2014 assessment criteria, patients must have measurable lesions, defined as the longest diameter of at least one nodule > 1.5cm, or the longest diameter of at least one nodule > 1cm, and at least two vertical diameters that can be accurately measured. Patients volunteered to participate in the trial, understood the study procedure, and were able to sign in-person informed consent. Exclusion Criteria: Patients with definite lymphoma central nervous system (CNS) infiltration, including brain parenchyma, meningeal invasion, or spinal cord compression; severe or uncontrolled infection; with active autoimmune disease; Other serious medical conditions, such as uncontrolled diabetes, gastric ulcers, other serious cardiopulmonary diseases, etc. (the decision was left to the investigator); patients who received the live attenuated vaccine within 4 weeks before the first dose or planned to receive the live attenuated vaccine during the study; The subject has previous or co -e xis ting other malignant tumors; Patients with basal cell carcinoma of the skin and uterine and neck carcinoma in situ who had been cured for more than 3 years, and patients with other malignant tumors who had been cured for more than 5 years were considered for inclusion. HIV-positive patients with active hepatitis B ( HBV-DNA > 100 copies/m L), positive HCV antibody, or abnormal HCV-RNA Women who were pregnant or lactating, women who planned to become pregnant between the study period and 6 months after the last dose, or men whose partners planned to become pregnant, who were unwilling to use a medically approve defective contraceptive method (e.g., intrauterine device or condom ) during the trial; were allergic to any of the drugs in the study protocol; ineligible for inclusion as judged by the investigator ;

Sites / Locations

  • Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Z-RCHOP

Arm Description

Patients with newly diagnosed DLBCL with p53 expression were treated with a combination of Zanubrutinib and RCHOP.

Outcomes

Primary Outcome Measures

Complete response rate (CRR)
To evaluate the efficacy of anti-lymphoma

Secondary Outcome Measures

Overall response rate (ORR)
To evaluate the efficacy of anti-lymphoma
Progression-free survival (PFS)
To evaluate the efficacy of anti-lymphoma
Overall survival (OS)
To evaluate the efficacy of anti-lymphoma
Rate of AE and SAE
To identify the incidence of AE and SAE in clinical trial

Full Information

First Posted
July 24, 2023
Last Updated
August 16, 2023
Sponsor
Huazhong University of Science and Technology
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1. Study Identification

Unique Protocol Identification Number
NCT06005870
Brief Title
Zanubrutinib Combined With R-CHOP in the Treatment of Newly Diagnosed DLBCL With p53 Protein Expression
Official Title
Zanubrutinib Combined With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in the Treatment of Newly Diagnosed Diffuse Large B-cell Lymphoma With p53 Protein Expression
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 26, 2022 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Huazhong University of Science and Technology

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No

5. Study Description

Brief Summary
This study aim to evaluate the efficacy and safety of zanubrutinib combined with R-CHOP in the treatment of DLBCL patients with p53 protein expression.
Detailed Description
This is a prospective, single arm, single center study,it plans to recruit 41 newly diagnosed DLBCL patients with p53 protein expression(≥50%).According to Simon's two-stage optimal design criteria, 19 eligible patients were recruited in the first phase, and at least 12 patients were required to achieve complete response to enter the second phase. In phase 2, additional 22 patients were recruited. These patients will receive zanubrutinib plus RCHOP for 6 cycles. After 4 treatment cycles, an interim response assessment will be performed to evaluate disease progression for each participant. Participants with progressive or stable disease will be discontinued from treatment,Participants with complete/partial response will continue ZRCHOP until 6 cycles are completed.After completion of study drug, participants will undergo assessment of tumor response based on the Revised Response Criteria for Malignant Lymphoma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B Cell Lymphoma
Keywords
DLBCL, Diffuse Large b-cell lymphoma, p53, zanubrutinib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
41 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Z-RCHOP
Arm Type
Experimental
Arm Description
Patients with newly diagnosed DLBCL with p53 expression were treated with a combination of Zanubrutinib and RCHOP.
Intervention Type
Drug
Intervention Name(s)
Zanubrutinib plus RCHOP
Intervention Description
Rituximab 375mg/m2 D1; cyclophosphamide 750mg/m2 D2; adriamycin 50 mg/m2 D2 vincristine 1.4mg/m(Max 2mg) D2; prednisone 100mg/d D2-6; Zanubrutinib 160 mg, the bid D1-21
Primary Outcome Measure Information:
Title
Complete response rate (CRR)
Description
To evaluate the efficacy of anti-lymphoma
Time Frame
At the end of cycle 6 (each cycle is 21 days )
Secondary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
To evaluate the efficacy of anti-lymphoma
Time Frame
At the end of cycle 6 (each cycle is 21 days )
Title
Progression-free survival (PFS)
Description
To evaluate the efficacy of anti-lymphoma
Time Frame
From date of initiation therapy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Title
Overall survival (OS)
Description
To evaluate the efficacy of anti-lymphoma
Time Frame
From date of initiation therapy until the date of death from any cause, assessed up to 60 months
Title
Rate of AE and SAE
Description
To identify the incidence of AE and SAE in clinical trial
Time Frame
from the initiation of the first dose to 28 days after the last dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥18 years, ≤ 75 years, both sexes; Diff use large B-cell lymphoma diagnosed by histopathology without previous systemic DLBCL treatment; ECOG score: 0-2; Predicted survival ≥3 months; Patients with positive p53 expression detected by immunohistochemistry (≥50% ); The patients had certain conditions of organ function reserve, and the laboratory tests within 1 week before enrollment met the following conditions: Blood routine: neutrophil count (NEUT) ≥1.5×10^9/L, platelet count (PLT) ≥75×10^9/L, hemoglobin (HGB) ≥80 g/L; G-CSF was not used in the past 7 days (the researchers judged that the lymphoma-induced cytopenia could be included). Liver function: Total bilirubin (TBIL) ≤1.5× upper limit of the normal range (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN; If liver metastases were present, TBIL≤3×ULN, ALT and AST≤5×ULN; Renal function: serum creatinine (Cr) ≤2.0×ULN or creatinine clearance (CCr) ≥60ml/min; Cardiac function: LVEF≥50%, ECG did not indicate any acute myocardial infarction, arrhythmia, or atrioventricular conduction block above grade I; Thyroid function: thyroid stimulating hormone (TSH) was within the normal range. If TSH is abnormal, free triiodothyronine (FT3) and free thyroxine (FT4) should be within the normal range or abnormal without clinical significance. According to the Lugano2014 assessment criteria, patients must have measurable lesions, defined as the longest diameter of at least one nodule > 1.5cm, or the longest diameter of at least one nodule > 1cm, and at least two vertical diameters that can be accurately measured. Patients volunteered to participate in the trial, understood the study procedure, and were able to sign in-person informed consent. Exclusion Criteria: Patients with definite lymphoma central nervous system (CNS) infiltration, including brain parenchyma, meningeal invasion, or spinal cord compression; severe or uncontrolled infection; with active autoimmune disease; Other serious medical conditions, such as uncontrolled diabetes, gastric ulcers, other serious cardiopulmonary diseases, etc. (the decision was left to the investigator); patients who received the live attenuated vaccine within 4 weeks before the first dose or planned to receive the live attenuated vaccine during the study; The subject has previous or co -e xis ting other malignant tumors; Patients with basal cell carcinoma of the skin and uterine and neck carcinoma in situ who had been cured for more than 3 years, and patients with other malignant tumors who had been cured for more than 5 years were considered for inclusion. HIV-positive patients with active hepatitis B ( HBV-DNA > 100 copies/m L), positive HCV antibody, or abnormal HCV-RNA Women who were pregnant or lactating, women who planned to become pregnant between the study period and 6 months after the last dose, or men whose partners planned to become pregnant, who were unwilling to use a medically approve defective contraceptive method (e.g., intrauterine device or condom ) during the trial; were allergic to any of the drugs in the study protocol; ineligible for inclusion as judged by the investigator ;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Liling Zhang, M.D
Phone
15871725926
Email
15871725926lily1228@sina.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Liling Zhang, M.D
Organizational Affiliation
Wuhan Union Hospital, China
Official's Role
Study Chair
Facility Information:
Facility Name
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430022
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Liling Zhang, M.D
Phone
15871725926
Email
15871725926lily1228@sina.com

12. IPD Sharing Statement

Learn more about this trial

Zanubrutinib Combined With R-CHOP in the Treatment of Newly Diagnosed DLBCL With p53 Protein Expression

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