Clinical trial NCT05428670: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Diffuse Large B Cell Lymphoma
Keywords: Diffuse Large B Cell Lymphoma
Zanubrutinib
Elderly patients
Lead sponsor: First Affiliated Hospital of Wenzhou Medical University
Sponsor class: OTHER
First posted: 2022-06-23
Enrollment: 150
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Complete response rate
timeFrame: At the end of Cycle 4 and Cycle 6 (each cycle is 21 days).
Secondary outcomes:
measure: Overall survival
timeFrame: Baseline up to data cut-off (up to approximately 3 years).
measure: Progression free survival
timeFrame: Baseline up to data cut-off (up to approximately 3 years).
measure: Incidence rate of adverse events
timeFrame: From enrollment to study completion, a maximum of 3 years.
measure: Direct medical costs
timeFrame: At the end of Cycle 4 and Cycle 6 (each cycle is 21 days).
measure: EQ-5D scores
timeFrame: At the end of Cycle 4 and Cycle 6 (each cycle is 21 days).
measure: Maximum plasma concentration
timeFrame: 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).
measure: Area under the plasma concentration-time curve
timeFrame: 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).
measure: Steady-state trough concentration
timeFrame: 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 outcomes:
measure: cfDNA sequencing
timeFrame: 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.
Locations:
city: Wenzhou
country: China
facility: First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
References: