non-Hodgkin white blood cells cancer
Conditions
Interventions
• Arm A: zanubrutinib plus rituximab for 6 cycles, followed by zanubrutinib
monotherapy
• Arm B: bendamustine plus rituximab for 6 cycles, followed by observation
Rituximab is given by intravenous (
Sponsors
BeiGene Ltd.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - >=*70 years of age at the time of informed consent, OR >= 60 and =*3 months - Adequate organ function (refer to Protocol Synopsis for more details) - Female patients of childbearing potential must practice highly effective methods of contraception - Male patients are eligible if abstinent, vasectomized or if they agree to the use of barrier contraception in combination with other methods - Ability to provide written informed consent and ability to understand and comply with the requirements of the study - For all patients irrespective of their age, Creatinine clearance of >= 30 mL/min
Exclusion criteria
Exclusion criteria: - Known central nervous system involvement by lymphoma - Prior hematopoietic stem cell transplantation - Prior exposure to a BTK inhibitor, rituximab, or bendamustine - Patients for whom the goal of therapy is tumor debulking prior to stem cell transplant - Prior malignancy within the past 3 years, except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score 6 prostate cancer - Clinically significant cardiovascular disease (for more details refer to the Protocol) - History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention - History of stroke or intracranial hemorrhage within 6 months before first dose of study drug - Unable to swallow capsules or disease significantly affecting gastrointestinal function - Active fungal, bacterial and/or viral infection requiring systemic therapy - Underlying medical conditions that, in the investigator*s opinion, will render the administration of study drug hazardous or obscure the interpretation of safety or efficacy results - Known infection with human immunodeficiency virus (HIV), or serologic status reflecting active hepatitis B or C infection (Refer to the Protocol for more details) - Major surgery within 4 weeks of the first dose of study drug - Pregnant or lactating women - Vaccination with a live vaccine within 35 days prior to the first dose of study drug - Ongoing alcohol or drug addiction - Hypersensitivity to zanubrutinib, bendamustine, or rituximab or any of the other ingredients of the study drugs - Requires ongoing treatment with a strong CYP3A inhibitor or inducer - Concurrent participation in another therapeutic clinical trial. - Patients enrolled in Germany only, who are severe immunocompromised
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary efficacy analysis of PFS will be conducted as assessed by independent central review, per the 2014 Lugano Classification for NHL. Progression-free survival will be compared between the 2 arms using a log-rank test stratified by MIPI score (low vs. intermediate or high), age (>= 70 years vs. = 1.17 HaN1: HR (Arm A/Arm B) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary efficacy endpoints will be analyzed and compared between the 2 treatment groups if the non inferiority test of the primary endpoint is significant either at the interim or final analyses. PFS, ORR, DOR, rate of CR or complete metabolic response, and time to response based on the assessment by independent central review as well as investigator assessment will be analyzed. • PFS by investigator assessment will be calculated based on investigator-assessed tumor responses. PFS by investigator assessment will be analyzed using the same analysis methods as the primary endpoint of PFS by independent central review. • ORR will be estimated as the crude proportion of patients in each treatment group who achieve partial response (PR) or higher. Associated 95% Clopper-Pearson confidence intervals will be calculated by treatment group. The odds ratio (and 95% confidence intervals), which will be provided as a measure of the relative treatment effect, will be estimated using the stratified Cochran-Mantel-Haenszel method. • Duration of response: The distribution of DOR, including median and other quartiles, will be estimated using the Kaplan-Meier method for each treatment group. Hypothesis testing comparing DOR between the 2 treatment groups will not be performed. • Overall survival: OS between the treatment groups will be compared using the same methods employed for the PFS comparison. • Rate of complete response or complete metabolic response will be analyzed using the same methods employed for ORR analysis. • Time to response will be summarized for each treatment group using sample statistics, such as sample mean, median, and standard deviation. • Patient-reported outcomes: The EORTC QLQ-C30 and EQ-5D-5L questionnaires will be utilized. The scores and their changes from baseline will be summarized and compared between the 2 treatment groups. | — |
Countries
Netherlands
Outcome results
None listed