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The Efficacy and Safety of ZR2 Versus R-CHOP-like Regimen for Elderly Patients With Newly Diagnosed Diffuse Large B Cell Lymphoma.

Primary Purpose

Diffuse Large B Cell Lymphoma

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Zanubrutinib+Rituximab+Lenalidomide
RCHOP/RCDOP
Sponsored by
First Affiliated Hospital of Wenzhou Medical University
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 Diffuse Large B Cell Lymphoma, Zanubrutinib, Elderly patients

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Pathologically confirmed DLBCL
  • Without treatment
  • ≥ 65 years old
  • Measurable lesions on CT or PET-CT before treatment
  • Life expectancy of at least 3 months
  • Voluntary participation with the consent of the patient
  • Heart, kidney, liver and other organ function evaluation were basically normal before treatment

Exclusion Criteria:

  • Patients who previously received chemotherapy
  • Uncontrolled cardiovascular diseases, cerebrovascular diseases, thrombotic diseases, autoimmune diseases and serious infectious diseases

  • Laboratory indicators before enrollment (unless caused by lymphoma):

    • Neutrophils < 1.5 × 10^9/L
    • Platelets < 80 × 10^9/L
    • Alanine aminotransferase or aspartate aminotransferase > 2 × ULN
    • Alkaline phosphatase or bilirubin > 1.5 × ULN
    • Creatinine > 1.5 × ULN
  • Patients who cannot comply with the agreement due to mental diseases or other unknown reasons such as pregnancy and lactation
  • HIV infection
  • If HBsAg is positive, HBVDNA should be tested, and patients with positive DNA cannot be enrolled; if HBsAg is negative and HBcAb is positive (regardless of HBsAb status), HBVDNA should be tested, and patients with positive DNA cannot be enrolled
  • Other uncontrolled medical conditions that may interfere with the study

Sites / Locations

  • First Affiliated Hospital of Wenzhou Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Zanubrutinib+Rituximab+Lenalidomide

RCHOP/RCDOP

Arm Description

The ZR2 regimen will be given from day 1 of each cycle of treatment. Each cycle will last for 21 days. Participants will receive a total of 6 cycles. Dosage: Zanubrutinib, 160 mg bid, po, day 2-21; Lenalidomide, 10-20 mg qd, po, day 2-14; Rituximab, 375 mg/m², ivgtt, day 1. Maintenance therapy: Patients who receive complete response or partial response after induction therapy will receive lenalidomide 10-20 mg qd po during 1-21 days in every 28 days, for a maximum of 2 years.

The RCHOP/RCDOP regimen will be given from day 1 of each cycle of treatment. Each cycle will last for 21 days. Participants will receive a total of 6 cycles. Dosage: Rituximab, 375 mg/m², ivgtt, day 1; Cyclophosphamide, 500-750 mg/m², ivgtt, day 2; Doxorubicin, 50 mg/m², ivgtt day 2 (liposomal doxorubicin, 20-30 mg/m², ivgtt day 2 or Epirubicin, 50-60 mg/m², ivgtt day 2); Vincristine, 1.4 mg/m², iv day 2 or vindesine, 3mg/m², iv day 2; Prednisone, 100 mg qd, po day 2-6.

Outcomes

Primary Outcome Measures

Complete response rate
Percentage of participants with complete response is determined on the basis of investigator assessments according to 2014 Lugano criteria.

Secondary Outcome Measures

Overall survival
Overall survival is defined as the time from the date of randomization to the date of death from any cause.
Progression free survival
Progression-free survival is defined as the time from the date of randomization until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria, or death from any cause, whichever occurred first.
Incidence rate of adverse events
Percentage of participants with treatment-related adverse events is assessed by CTCAEv4.0.
Direct medical costs
Direct medical costs include personal expenses and medical insurance reimbursement expenses, mainly including examination expenses, disposal expenses, medical expenses, hospitalization expenses, and other expenses.
EQ-5D scores
EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) is calculated for the pharmacoeconomics analysis to evaluate the quality of life in participants. EQ-5D is a participant answered questionnaire scoring 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ-5D total score ranges from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome.
Maximum plasma concentration
Maximum plasma concentration (Cmax) is defined as maximum plasma concentration after dose.
Area under the plasma concentration-time curve
Area under the plasma concentration-time curve (AUC) is defined as the area under the curve from time zero to time of last quantifiable plasma concentration after dose.
Steady-state trough concentration
Steady-state trough concentration (Css,min) is defined as minimum plasma concentration after dose.

Full Information

First Posted
June 2, 2022
Last Updated
June 20, 2022
Sponsor
First Affiliated Hospital of Wenzhou Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT05428670
Brief Title
The Efficacy and Safety of ZR2 Versus R-CHOP-like Regimen for Elderly Patients With Newly Diagnosed Diffuse Large B Cell Lymphoma.
Official Title
The Efficacy and Safety of ZR2 Versus R-CHOP-like Regimen for Elderly Patients With Newly Diagnosed Diffuse Large B Cell Lymphoma.
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 15, 2022 (Anticipated)
Primary Completion Date
May 30, 2025 (Anticipated)
Study Completion Date
June 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
First Affiliated Hospital of Wenzhou Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a prospective, single-center, open-label clinical study designed to evaluate the efficacy and safety of the Zanubrutinib, Lenalidomide and Rituximab (ZR2) versus rituximab combined with CHOP or CDOP (R-CHOP or R-CDOP) in elderly patients with diffuse large B cell lymphoma treated for the first time.
Detailed Description
In this study, elderly DLBCL patients will be treated with ZR2 regimen for the first-line treatment. Investigators will compare the complete response rate, survival and incidence of adverse reactions between the RCHOP/RCDOP chemotherapy and the ZR2 regimen. In addition, immune function tests will be performed before treatment and every 2 courses after treatment, including peripheral blood lymphocyte-monocyte ratio, cytokines, immunoglobulins, T and B cells and their quantitative analysis. Patients with ZR2 regimen will undergo gene second-generation sequencing before treatment to compare the gene mutation differences between complete response (CR) and ≤ partial response (PR) in the efficacy of ZR2 regimen, in order to find biomarkers with better efficacy in ZR2 treatment. Moreover, investigators intend to conduct pharmacokinetics/pharmacodynamics (PK/PD) correlation analysis of ZR2 regimen and pharmacoeconomic evaluation of the two regimens.

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
Diffuse Large B Cell Lymphoma, Zanubrutinib, Elderly patients

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Zanubrutinib+Rituximab+Lenalidomide
Arm Type
Experimental
Arm Description
The ZR2 regimen will be given from day 1 of each cycle of treatment. Each cycle will last for 21 days. Participants will receive a total of 6 cycles. Dosage: Zanubrutinib, 160 mg bid, po, day 2-21; Lenalidomide, 10-20 mg qd, po, day 2-14; Rituximab, 375 mg/m², ivgtt, day 1. Maintenance therapy: Patients who receive complete response or partial response after induction therapy will receive lenalidomide 10-20 mg qd po during 1-21 days in every 28 days, for a maximum of 2 years.
Arm Title
RCHOP/RCDOP
Arm Type
Active Comparator
Arm Description
The RCHOP/RCDOP regimen will be given from day 1 of each cycle of treatment. Each cycle will last for 21 days. Participants will receive a total of 6 cycles. Dosage: Rituximab, 375 mg/m², ivgtt, day 1; Cyclophosphamide, 500-750 mg/m², ivgtt, day 2; Doxorubicin, 50 mg/m², ivgtt day 2 (liposomal doxorubicin, 20-30 mg/m², ivgtt day 2 or Epirubicin, 50-60 mg/m², ivgtt day 2); Vincristine, 1.4 mg/m², iv day 2 or vindesine, 3mg/m², iv day 2; Prednisone, 100 mg qd, po day 2-6.
Intervention Type
Drug
Intervention Name(s)
Zanubrutinib+Rituximab+Lenalidomide
Intervention Description
Zanubrutinib is a bruton' s tyrosine kinase inhibitor independently developed in China.
Intervention Type
Drug
Intervention Name(s)
RCHOP/RCDOP
Intervention Description
RCHOP/RCDOP is the classic treatment of diffuse large B cell lymphoma.
Primary Outcome Measure Information:
Title
Complete response rate
Description
Percentage of participants with complete response is determined on the basis of investigator assessments according to 2014 Lugano criteria.
Time Frame
At the end of Cycle 4 and Cycle 6 (each cycle is 21 days).
Secondary Outcome Measure Information:
Title
Overall survival
Description
Overall survival is defined as the time from the date of randomization to the date of death from any cause.
Time Frame
Baseline up to data cut-off (up to approximately 3 years).
Title
Progression free survival
Description
Progression-free survival is defined as the time from the date of randomization until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria, or death from any cause, whichever occurred first.
Time Frame
Baseline up to data cut-off (up to approximately 3 years).
Title
Incidence rate of adverse events
Description
Percentage of participants with treatment-related adverse events is assessed by CTCAEv4.0.
Time Frame
From enrollment to study completion, a maximum of 3 years.
Title
Direct medical costs
Description
Direct medical costs include personal expenses and medical insurance reimbursement expenses, mainly including examination expenses, disposal expenses, medical expenses, hospitalization expenses, and other expenses.
Time Frame
At the end of Cycle 4 and Cycle 6 (each cycle is 21 days).
Title
EQ-5D scores
Description
EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) is calculated for the pharmacoeconomics analysis to evaluate the quality of life in participants. EQ-5D is a participant answered questionnaire scoring 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ-5D total score ranges from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome.
Time Frame
At the end of Cycle 4 and Cycle 6 (each cycle is 21 days).
Title
Maximum plasma concentration
Description
Maximum plasma concentration (Cmax) is defined as maximum plasma concentration after dose.
Time Frame
The Cmax of zanubrutinib is determined at 2h postdose on day 2 of Cycle 2 (each cycle is 21 days) and the Cmax of lenalidomide is determined at 1h postdose on day 2 of Cycle 2 (each cycle is 21 days).
Title
Area under the plasma concentration-time curve
Description
Area under the plasma concentration-time curve (AUC) is defined as the area under the curve from time zero to time of last quantifiable plasma concentration after dose.
Time Frame
The AUC of zanubrutinib is determined at predose (0h), 2h and 24h postdose on day 2 of Cycle 2 (each cycle is 21 days) and the AUC of lenalidomide is determined at predose (0h), 1h and 24h postdose on day 2 of Cycle 2 (each cycle is 21 days).
Title
Steady-state trough concentration
Description
Steady-state trough concentration (Css,min) is defined as minimum plasma concentration after dose.
Time Frame
The Css,min of zanubrutinib is determined at 24h postdose on day 2 of Cycle 2 (each cycle is 21 days) and the Css,min of lenalidomide is determined at 24h postdose on day 2 of Cycle 2 (each cycle is 21 days).
Other Pre-specified Outcome Measures:
Title
cfDNA sequencing
Description
Cell free deoxyribonucleic acid sequencing in peripheral blood samples
Time Frame
Before treatment, at the end of Cycle 4 (each cycle is 21 days) and Cycle 6, and then every 6 months after the end of Cycle 6, a maximum of 2 years.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Pathologically confirmed DLBCL Without treatment ≥ 65 years old Measurable lesions on CT or PET-CT before treatment Life expectancy of at least 3 months Voluntary participation with the consent of the patient Heart, kidney, liver and other organ function evaluation were basically normal before treatment Exclusion Criteria: Patients who previously received chemotherapy Uncontrolled cardiovascular diseases, cerebrovascular diseases, thrombotic diseases, autoimmune diseases and serious infectious diseases Laboratory indicators before enrollment (unless caused by lymphoma): Neutrophils < 1.5 × 10^9/L Platelets < 80 × 10^9/L Alanine aminotransferase or aspartate aminotransferase > 2 × ULN Alkaline phosphatase or bilirubin > 1.5 × ULN Creatinine > 1.5 × ULN Patients who cannot comply with the agreement due to mental diseases or other unknown reasons such as pregnancy and lactation HIV infection If HBsAg is positive, HBVDNA should be tested, and patients with positive DNA cannot be enrolled; if HBsAg is negative and HBcAb is positive (regardless of HBsAb status), HBVDNA should be tested, and patients with positive DNA cannot be enrolled Other uncontrolled medical conditions that may interfere with the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Haige Ye, Ph.D
Phone
+8615967413188
Email
haigeye@wzhospital.cn
Facility Information:
Facility Name
First Affiliated Hospital of Wenzhou Medical University
City
Wenzhou
State/Province
Zhejiang
ZIP/Postal Code
325000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xian Shen, Ph. D
Phone
+86057755578055
Email
wyyyclinical@126.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

The Efficacy and Safety of ZR2 Versus R-CHOP-like Regimen for Elderly Patients With Newly Diagnosed Diffuse Large B Cell Lymphoma.

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