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

June 20, 2022 updated by: Haige Ye, First Affiliated Hospital of Wenzhou Medical University
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

150

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Zhejiang
      • Wenzhou, Zhejiang, China, 325000
        • Recruiting
        • First Affiliated Hospital of Wenzhou Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

65 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Zanubrutinib+Rituximab+Lenalidomide

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.
Drug: Zanubrutinib+Rituximab+Lenalidomide
Zanubrutinib is a bruton' s tyrosine kinase inhibitor independently developed in China.
Active Comparator: RCHOP/RCDOP

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.
Drug: RCHOP/RCDOP
RCHOP/RCDOP is the classic treatment of diffuse large B cell lymphoma.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete response rate
Time Frame: At the end of Cycle 4 and Cycle 6 (each cycle is 21 days).
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: Baseline up to data cut-off (up to approximately 3 years).
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).
Progression free survival
Time Frame: Baseline up to data cut-off (up to approximately 3 years).
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).
Incidence rate of adverse events
Time Frame: From enrollment to study completion, a maximum of 3 years.
Percentage of participants with treatment-related adverse events is assessed by CTCAEv4.0.
From enrollment to study completion, a maximum of 3 years.
Direct medical costs
Time Frame: At the end of Cycle 4 and Cycle 6 (each cycle is 21 days).
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).
EQ-5D scores
Time Frame: At the end of Cycle 4 and Cycle 6 (each cycle is 21 days).
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).
Maximum plasma concentration
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).
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).
Area under the plasma concentration-time curve
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).
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).
Steady-state trough concentration
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).
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).

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
cfDNA sequencing
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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

First Affiliated Hospital of Wenzhou Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

June 15, 2022

Primary Completion (Anticipated)

May 30, 2025

Study Completion (Anticipated)

June 30, 2025

Study Registration Dates

First Submitted

June 2, 2022

First Submitted That Met QC Criteria

June 20, 2022

First Posted (Actual)

June 23, 2022

Study Record Updates

Last Update Posted (Actual)

June 23, 2022

Last Update Submitted That Met QC Criteria

June 20, 2022

Last Verified

June 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HaigeYe

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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