Diffuse Large B-Cell LymphomaPhase 3NCT05179733
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
A Phase 3 study testing six courses of zanubrutinib, rituximab and lenalidomide and six courses of rituximab combined with low-dose CHOP in people with Diffuse Large B-Cell Lymphoma, run by Ruijin Hospital at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 70 years and older
- Conditions the study is for
- Diffuse Large B-Cell Lymphoma
- What is being tested?
- six courses of zanubrutinib, rituximab and lenalidomide and six courses of rituximab combined with low-dose CHOP
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 280 participants
- Where
- 1 siteChina
- Study dates
- 2 Mar 2022to 25 Dec 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 70 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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)
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- 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).
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Ruijin Hospital
Shanghai, Shanghai Municipality, 200020
Weili ZHAO, +862164370045 ext. 610707, zwl_trial@163.com
About this study
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
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
Read the 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.
- Conditions
- Diffuse Large B-Cell Lymphoma
- Being tested
- six courses of zanubrutinib, rituximab and lenalidomide, six courses of rituximab combined with low-dose CHOP
- Keywords
- Diffuse Large B-Cell Lymphoma, Elderly patients, Zanubrutinib, Lenalidomide, Rituximab, R-miniCHOP
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
six courses of zanubrutinib, rituximab and lenalidomideDrug
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.
six courses of rituximab combined with low-dose CHOPDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| ZR2 | Experimental | six courses of zanubrutinib, rituximab and lenalidomide Receives: Drug: six courses of zanubrutinib, rituximab and lenalidomide |
| R-miniCHOP | Active comparator | six courses of rituximab combined with low-dose CHOP Receives: Drug: six courses of rituximab combined with low-dose CHOP |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline up to data cut-off (up to approximately 2 years)
Secondary outcomes (6)
Complete response rate
Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria.
Measured: At the end of Cycle 6 (each cycle is 21 days)
Overall survival
Overall survival was defined as the time from the date of randomization to the date of death from any cause.
Measured: Baseline up to data cut-off (up to approximately 2 years)
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.
Measured: From enrollment to study completion, a maximum of 4 years
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).
Measured: Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion
Percentage of Participants Achieving Meaningful Improvement in EORTC QLQ-ELD14 (Elderly Module)
Quality of Life will be assessed by EORTC QLQ-ELD14.
Measured: Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion
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.
Measured: Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2022
- Study start2 Mar 2022
- Primary completion25 Dec 2025 (estimated)
- Study completion25 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Large B-Cell LymphomaStudies of the same condition, open and under way.
- More trials run by Ruijin HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 280 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ruijin Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 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, Sir Run Run Shaw Hospital, Northern Jiangsu 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
- Responsible party
- Principal investigator, Zhao Weili, Ruijin Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05179733
- Sponsor's protocol ID
- NHL-014
- Status last verified
- May 2023
- First submitted
- 22 Nov 2021
- Last updated
- 23 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05179733
- Acronym / sponsor ID
- NHL-014
- Conditions
- Diffuse Large B-Cell Lymphoma
- Keywords
- Diffuse Large B-Cell Lymphoma, Elderly patients, Zanubrutinib, Lenalidomide, Rituximab, R-miniCHOP
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 280 participants (estimated)
- Lead sponsor
- Ruijin HospitalUniversity, hospital or other
- Collaborators
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 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, Sir Run Run Shaw Hospital, Northern Jiangsu 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
- Study start
- 2 Mar 2022 (actual)
- Primary completion
- 25 Dec 2025 (estimated)
- Study completion
- 25 Dec 2025 (estimated)
- First posted
- 5 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ZR2 | Experimental | Drug: six courses of zanubrutinib, rituximab and lenalidomidesix courses of zanubrutinib, rituximab and lenalidomide |
| R-miniCHOP | Active comparator | Drug: six courses of rituximab combined with low-dose CHOPsix courses of rituximab combined with low-dose CHOP |
Who may qualify
- Ages
- 70 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (9 listed)
- 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)
Key exclusion criteria (16 listed)
- 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):
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| six courses of zanubrutinib, rituximab and lenalidomidePatients 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. | Drug | ZR2 |
| six courses of rituximab combined with low-dose CHOPPatients 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. | Drug | R-miniCHOP |
Primary outcome
Progression free survival
Time frame: Baseline up to data cut-off (up to approximately 2 years)
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.
6 secondary outcomes
Complete response rate
Time frame: At the end of Cycle 6 (each cycle is 21 days)
Overall survival
Time frame: Baseline up to data cut-off (up to approximately 2 years)
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0
Time frame: From enrollment to study completion, a maximum of 4 years
Percentage of Participants Achieving Meaningful Improvement in European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30)
Time frame: Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion
Percentage of Participants Achieving Meaningful Improvement in EORTC QLQ-ELD14 (Elderly Module)
Time frame: Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion
Percentage of Participants Achieving Meaningful Improvement in Functional Assessment of Cancer Therapy-Lymphoma Lymphoma Subscale (FACT-Lym LymS)
Time frame: Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing six courses of zanubrutinib, rituximab and lenalidomide and six courses of rituximab combined with low-dose CHOP in people with Diffuse Large B-Cell Lymphoma, run by Ruijin Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Weili ZHAO (+862164370045 ext. 610707, zwl_trial@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (time frame: Baseline up to data cut-off (up to approximately 2 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2023.