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

Diffuse Large B Cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05428670
• Other study ID #: HaigeYe
• Status: Recruiting
• Phase: Phase 2
• Start date: June 15, 2022
• Est. completion date: June 30, 2025

Study information

• Verified date: June 2022
• Source: First Affiliated Hospital of Wenzhou Medical University
• Contact: Haige Ye, Ph.D
• Phone: +8615967413188
• Email: haigeye[@]wzhospital.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: June 30, 2025
• Est. primary completion date: May 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diffuse Large B Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Zanubrutinib+Rituximab+Lenalidomide
Zanubrutinib is a bruton' s tyrosine kinase inhibitor independently developed in China.
• RCHOP/RCDOP
RCHOP/RCDOP is the classic treatment of diffuse large B cell lymphoma.

Locations

Country	Name	City	State
China	First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
First Affiliated Hospital of Wenzhou Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	cfDNA sequencing	Cell free deoxyribonucleic acid sequencing in peripheral blood samples	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.
Primary	Complete response rate	Percentage of participants with complete response is determined on the basis of investigator assessments according to 2014 Lugano criteria.	At the end of Cycle 4 and Cycle 6 (each cycle is 21 days).
Secondary	Overall survival	Overall survival is defined as the time from the date of randomization to the date of death from any cause.	Baseline up to data cut-off (up to approximately 3 years).
Secondary	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.	Baseline up to data cut-off (up to approximately 3 years).
Secondary	Incidence rate of adverse events	Percentage of participants with treatment-related adverse events is assessed by CTCAEv4.0.	From enrollment to study completion, a maximum of 3 years.
Secondary	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.	At the end of Cycle 4 and Cycle 6 (each cycle is 21 days).
Secondary	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.	At the end of Cycle 4 and Cycle 6 (each cycle is 21 days).
Secondary	Maximum plasma concentration	Maximum plasma concentration (Cmax) is defined as maximum plasma concentration after dose.	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).
Secondary	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.	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).
Secondary	Steady-state trough concentration	Steady-state trough concentration (Css,min) is defined as minimum plasma concentration after dose.	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).