Back to resultsThe Efficacy and Safety of ZR2 Versus R-miniCHOP in the Treatment of Unfit or Frail de Novo Diffuse Large B-cell Lymphoma Patients Aged Older Than or Equal to 70 Years
Primary Purpose
Diffuse Large B-Cell Lymphoma
Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
six courses of zanubrutinib, rituximab and lenalidomide
six courses of rituximab combined with low-dose CHOP
Sponsored by
About this trial
This is an interventional treatment trial for Diffuse Large B-Cell Lymphoma focused on measuring Diffuse Large B-Cell Lymphoma, Elderly patients, Zanubrutinib, Lenalidomide, Rituximab, R-miniCHOP
Eligibility Criteria
Inclusion Criteria
Patients must satisfy all of the following criteria to be enrolled in the study:
- Histologically-confirmed diffuse large B-cell lymphoma (without central nervous system involvement)
- Eastern Cooperative Oncology Group performance status 0-3
- Aged ≥ 80 years old or aged 70-79 with comprehensive geriatric assessment stratified as unfit or frail
- International normalized ratio and activated partial thromboplastin time are both 1.5 times lower than the upper limits of normal (ULN).
- At least 1 measurable site of disease (defined as lymph nodes with the long diameters longer than 1.5cm, or extra-nodal sites with the long diameters longer than 1.0cm; meanwhile, any lesion site with at least 2 measurable vertical diameters)
- Life expectancy of at least 3 months determined by researchers
- The patient or his or her legal representative must provide written informed consent prior to any special examination or procedure for the research.
- Anti-lymphoma drugs have not been used before (except glucocorticoids).
Exclusion criteria
Presence of any of the following criteria will exclude a patient from enrollment:
- Uncontrolled cardio- and cerebro-vascular disease, blood clotting disorders, connective tissue diseases, serious infectious diseases and other diseases
Laboratory measures meet the following criteria at screening (unless caused by lymphoma):
- Neutrophils<1.5×10^9/L
- Platelets<80×10^9/L (Platelets<50×10^9/L in case of bone marrow involvement)
- ALT or AST is 2 times higher than the upper limits of normal (ULN), AKP and bilirubin are 1.5 times higher than the ULN.
- Creatinine is 1.5 times higher than the ULN or eGFR is lower than 40ml/min/1.73m^2 (according to Cockcroft-Gault Equation or MDRD Equation).
- HIV-infected patients
- Left ventricular ejection fraction<50%
- Patients with HbsAg positive are required to have HBV DNA<1.0×10^3 IU/ml before entering the group. In addition, if the patient is HBsAg negative but HBcAb positive (regardless of HBsAb status), HBV DNA test is also required, and HBV DNA<1.0×10^3 IU/ml is required before entering the group.
- Other anti-tumor treatments (lymphoma or other types of tumors) are currently in progress.
- Patients with psychiatric disorders or patients who are known or suspected to be unable to fully comply with the study protocol
- Require treatment with strong/moderate CYP3A inhibitors or inducers.
- History of stroke or intracranial hemorrhage within 6 months prior to start of therapy
- Inability to swallow capsules or presence of diseases that significantly affect gastrointestinal function, such as malabsorption syndrome, post-bariatric surgery, inflammatory bowel disease and complete or incomplete intestinal obstruction
- Other medical conditions determined by the researchers that may affect the study
Sites / Locations
- Ruijin HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
ZR2
R-miniCHOP
Arm Description
six courses of zanubrutinib, rituximab and lenalidomide
six courses of rituximab combined with low-dose CHOP
Outcomes
Primary Outcome Measures
Progression free survival
Progression-free survival was 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.
Secondary Outcome Measures
Complete response rate
Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria.
Overall survival
Overall survival was defined as the time from the date of randomization to the date of death from any cause.
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Percentage of Participants Achieving Meaningful Improvement in European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30)
Quality of Life will be assessed by EORTC QLQ-C30 (Verison 3.0).
Percentage of Participants Achieving Meaningful Improvement in EORTC QLQ-ELD14 (Elderly Module)
Quality of Life will be assessed by EORTC QLQ-ELD14.
Percentage of Participants Achieving Meaningful Improvement in Functional Assessment of Cancer Therapy-Lymphoma Lymphoma Subscale (FACT-Lym LymS)
Quality of Life will be assessed by FACT-Lym LymS.
Full Information
NCT ID
NCT05179733
First Posted
November 22, 2021
Last Updated
May 20, 2023
Sponsor
Ruijin Hospital
Collaborators
Wuhan Union Hospital, China, Ningbo No. 1 Hospital, National Naval Medical Center, Shanghai Fengxian District Central Hospital, YANCHENG NO.1 PEOPLE'S HOSPITAL, The First Affiliated Hospital of Nanchang University, Affiliated Hospital of Nantong University, Wuxi Branch of Ruijin Hospital, Sir Run Run Shaw Hospital, Northern Jiangsu Province People's Hospital, The First People's Hospital of Changde City, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Changzhou No.2 People's Hospital, The Affiliated Hospital of Xuzhou Medical University, Huai'an First People's Hospital, Taizhou Hospital, The First People's Hospital of Kunshan, First Affiliated Hospital of Fujian Medical University, Huadong Hospital, Henan Provincial People's Hospital, First Hospital of China Medical University, Shandong Provincial Hospital, HARBIN THE FIRST HOSPITAL, The First Hospital of Jilin University, Hunan Cancer Hospital, Qilu Hospital of Shandong University, THE FIRST AFFILIATED HOSPITAL, The Second Affiliated Hospital of Dalian Medical University, SUZHOU HONGCI HEMATOLOGY HOSPITAL
1. Study Identification
Unique Protocol Identification Number
NCT05179733
Brief Title
The Efficacy and Safety of ZR2 Versus R-miniCHOP in the Treatment of Unfit or Frail de Novo Diffuse Large B-cell Lymphoma Patients Aged Older Than or Equal to 70 Years
Official Title
The Efficacy and Safety of Zanubrutinib, Rituximab and Lenalidomide (ZR2) Versus Rituximab Combined With Low-dose CHOP (R-miniCHOP) in the Treatment of Unfit or Frail de Novo Diffuse Large B-cell Lymphoma Patients Aged Older Than or Equal to 70 Years: A Multicenter, Prospective, Randomized, Open-label, Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 2, 2022 (Actual)
Primary Completion Date
December 25, 2025 (Anticipated)
Study Completion Date
December 25, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ruijin Hospital
Collaborators
Wuhan Union Hospital, China, Ningbo No. 1 Hospital, National Naval Medical Center, Shanghai Fengxian District Central Hospital, YANCHENG NO.1 PEOPLE'S HOSPITAL, The First Affiliated Hospital of Nanchang University, Affiliated Hospital of Nantong University, Wuxi Branch of Ruijin Hospital, Sir Run Run Shaw Hospital, Northern Jiangsu Province People's Hospital, The First People's Hospital of Changde City, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Changzhou No.2 People's Hospital, The Affiliated Hospital of Xuzhou Medical University, Huai'an First People's Hospital, Taizhou Hospital, The First People's Hospital of Kunshan, First Affiliated Hospital of Fujian Medical University, Huadong Hospital, Henan Provincial People's Hospital, First Hospital of China Medical University, Shandong Provincial Hospital, HARBIN THE FIRST HOSPITAL, The First Hospital of Jilin University, Hunan Cancer Hospital, Qilu Hospital of Shandong University, THE FIRST AFFILIATED HOSPITAL, The Second Affiliated Hospital of Dalian Medical University, SUZHOU HONGCI HEMATOLOGY HOSPITAL
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A multicenter, prospective, randomized, open-label, controlled trial to evaluate the efficacy and safety of zanubrutinib, rituximab and lenalidomide (ZR2) versus rituximab combined with low-dose CHOP (R-miniCHOP) in the treatment of unfit or frail de novo diffuse large B-cell lymphoma patients aged older than or equal to 70 years
Detailed Description
This study will evaluate the efficacy and safety of ZR2 versus R-miniCHOP in the treatment of unfit or frail de novo diffuse large B-cell lymphoma patients aged older than or equal to 70 years. Subjects will be randomly assigned 1:1 to ZR2 or R-miniCHOP regimen. The stratification will be performed according to international prognostic index (0-2 / 3-5).
Patients in ZR2 group will receive 6 cycles of zanubrutinib 160mg bid, day 1-21, orally, lenalidomide 25mg qd, day 2-11, orally, rituximab 375mg/m², day 1, intravenously, every 21 days. Patients in R-miniCHOP group will receive rituximab 375 mg/m² on day 1, cyclophosphamide 400 mg/m², doxorubicin 25 mg/m², and vincristine 1 mg on day 2, and prednisone 40 mg/m² on days 2-6, every 21 days.
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, Elderly patients, Zanubrutinib, Lenalidomide, Rituximab, R-miniCHOP
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
280 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ZR2
Arm Type
Experimental
Arm Description
six courses of zanubrutinib, rituximab and lenalidomide
Arm Title
R-miniCHOP
Arm Type
Active Comparator
Arm Description
six courses of rituximab combined with low-dose CHOP
Intervention Type
Drug
Intervention Name(s)
six courses of zanubrutinib, rituximab and lenalidomide
Intervention Description
Patients in ZR2 group will receive 6 cycles of zanubrutinib 160mg bid, day 1-21, orally, lenalidomide 25mg qd, day 2-11, orally, rituximab 375mg/m², day 1, intravenously, every 21 days.
Intervention Type
Drug
Intervention Name(s)
six courses of rituximab combined with low-dose CHOP
Intervention Description
Patients in R-miniCHOP group will receive rituximab 375 mg/m² on day 1, cyclophosphamide 400 mg/m², doxorubicin 25 mg/m², and vincristine 1 mg on day 2, and prednisone 40 mg/m² on days 2-6, every 21 days.
Primary Outcome Measure Information:
Title
Progression free survival
Description
Progression-free survival was 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 2 years)
Secondary Outcome Measure Information:
Title
Complete response rate
Description
Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria.
Time Frame
At the end of Cycle 6 (each cycle is 21 days)
Title
Overall survival
Description
Overall survival was 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 2 years)
Title
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0
Description
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time Frame
From enrollment to study completion, a maximum of 4 years
Title
Percentage of Participants Achieving Meaningful Improvement in European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30)
Description
Quality of Life will be assessed by EORTC QLQ-C30 (Verison 3.0).
Time Frame
Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion
Title
Percentage of Participants Achieving Meaningful Improvement in EORTC QLQ-ELD14 (Elderly Module)
Description
Quality of Life will be assessed by EORTC QLQ-ELD14.
Time Frame
Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion
Title
Percentage of Participants Achieving Meaningful Improvement in Functional Assessment of Cancer Therapy-Lymphoma Lymphoma Subscale (FACT-Lym LymS)
Description
Quality of Life will be assessed by FACT-Lym LymS.
Time Frame
Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Patients must satisfy all of the following criteria to be enrolled in the study:
Histologically-confirmed diffuse large B-cell lymphoma (without central nervous system involvement)
Eastern Cooperative Oncology Group performance status 0-3
Aged ≥ 80 years old or aged 70-79 with comprehensive geriatric assessment stratified as unfit or frail
International normalized ratio and activated partial thromboplastin time are both 1.5 times lower than the upper limits of normal (ULN).
At least 1 measurable site of disease (defined as lymph nodes with the long diameters longer than 1.5cm, or extra-nodal sites with the long diameters longer than 1.0cm; meanwhile, any lesion site with at least 2 measurable vertical diameters)
Life expectancy of at least 3 months determined by researchers
The patient or his or her legal representative must provide written informed consent prior to any special examination or procedure for the research.
Anti-lymphoma drugs have not been used before (except glucocorticoids).
Exclusion criteria
Presence of any of the following criteria will exclude a patient from enrollment:
Uncontrolled cardio- and cerebro-vascular disease, blood clotting disorders, connective tissue diseases, serious infectious diseases and other diseases
Laboratory measures meet the following criteria at screening (unless caused by lymphoma):
Neutrophils<1.5×10^9/L
Platelets<80×10^9/L (Platelets<50×10^9/L in case of bone marrow involvement)
ALT or AST is 2 times higher than the upper limits of normal (ULN), AKP and bilirubin are 1.5 times higher than the ULN.
Creatinine is 1.5 times higher than the ULN or eGFR is lower than 40ml/min/1.73m^2 (according to Cockcroft-Gault Equation or MDRD Equation).
HIV-infected patients
Left ventricular ejection fraction<50%
Patients with HbsAg positive are required to have HBV DNA<1.0×10^3 IU/ml before entering the group. In addition, if the patient is HBsAg negative but HBcAb positive (regardless of HBsAb status), HBV DNA test is also required, and HBV DNA<1.0×10^3 IU/ml is required before entering the group.
Other anti-tumor treatments (lymphoma or other types of tumors) are currently in progress.
Patients with psychiatric disorders or patients who are known or suspected to be unable to fully comply with the study protocol
Require treatment with strong/moderate CYP3A inhibitors or inducers.
History of stroke or intracranial hemorrhage within 6 months prior to start of therapy
Inability to swallow capsules or presence of diseases that significantly affect gastrointestinal function, such as malabsorption syndrome, post-bariatric surgery, inflammatory bowel disease and complete or incomplete intestinal obstruction
Other medical conditions determined by the researchers that may affect the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Weili ZHAO
Phone
+862164370045
Ext
610707
Email
zwl_trial@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Pengpeng XU
Phone
+862164370045
Ext
610707
Email
pengpeng_xu@126.com
Facility Information:
Facility Name
Ruijin Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200020
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Weili ZHAO
Phone
+862164370045
Ext
610707
Email
zwl_trial@163.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
The Efficacy and Safety of ZR2 Versus R-miniCHOP in the Treatment of Unfit or Frail de Novo Diffuse Large B-cell Lymphoma Patients Aged Older Than or Equal to 70 Years
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