Diffuse Large B-Cell LymphomaPhase 3NCT06522555
The Efficacy and Safety of Pola-ZR2 Versus ZR2 in the Treatment of Old Patients With de Novo Diffuse Large B-cell Lymphoma
A Phase 3 study testing polatuzumab vedotin, zanubrutinib, rituximab and lenalidomide and zanubrutinib, rituximab and lenalidomide 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 Pola-ZR2 (polatuzumab vedotin, zanubrutinib, rituximab and lenalidomide) versus ZR2 (zanubrutinib, rituximab and lenalidomide) in the treatment of old patients with de novo diffuse large B-cell lymphoma 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?
- polatuzumab vedotin, zanubrutinib, rituximab and lenalidomide and zanubrutinib, rituximab and lenalidomide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- 29 Jul 2024to 10 Aug 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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)
- Aged ≥ 80 years old or aged 70-79 with comprehensive geriatric assessment stratified as unfit or frail
- International prognostic index score 2 to 5
- 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)
- Able to swallow capsules
Show all 9Show fewer
- 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 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 ALT or AST is 2 times higher than the upper limits of normal (ULN), serum 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).
- uncontrollable or significant cardiovascular diseases, including but not limited to: Left ventricular ejection fraction<50% Cardiomyopathy, such as dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy QTc prolongation with clinical significance, QTc interval>470ms (females) or 480ms (males), type 2 second-degree atrioventricular block or third-degree atrioventricular block
Show all 11Show fewer
- 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
- Patients with psychiatric disorders or patients who are known or suspected to be unable to fully comply with the study protocol
- HIV-infected patients
- History of stroke or intracranial hemorrhage within 6 months prior to start of therapy
- Other medical conditions determined by the researchers that may affect the study
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Shanghai Institute of Hematology, Rui-Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai, 200025
Weili Zhao, +862164370045 ext. 610707, zwl_trial@163.com
Pengpeng Xu, +862164370045 ext. 610707, pengpeng_xu@126.com
About this study
Official title: The Efficacy and Safety of Pola-ZR2 (Polatuzumab Vedotin, Zanubrutinib, Rituximab and Lenalidomide) Versus ZR2 (Zanubrutinib, Rituximab and Lenalidomide) in the Treatment of Old Patients With de Novo Diffuse Large B-cell Lymphoma: A Multicenter, Prospective, Randomized, Open-label, Controlled Trial
A multicenter, prospective, randomized, open-label, controlled trial to evaluate the efficacy and safety of Pola-ZR2 (polatuzumab vedotin, zanubrutinib, rituximab and lenalidomide) versus ZR2 (zanubrutinib, rituximab and lenalidomide) in the treatment of old patients with de novo diffuse large B-cell lymphoma
Read the detailed description
This study will evaluate the efficacy and safety of Pola-ZR2 versus ZR2 in the treatment of elderly de novo diffuse large B-cell lymphoma patients. Subjects will be randomly assigned 1:1 to Pola-ZR2 or ZR2 regimen. The stratification will be performed according to international prognostic index (2-3 / 4-5).
Patients in Pola-ZR2 group will receive 6 cycles of polatuzumab vedotin 1.8 mg/kg, day 2 on the 1st cycle and day 1 on the 2nd to 6th cycle, 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 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 who receive complete response or partial response after induction therapy will receive lenalidomide 25 mg qd po during 1-10 days in every 21 days for 2 years.
- Conditions
- Diffuse Large B-Cell Lymphoma
- Being tested
- polatuzumab vedotin, zanubrutinib, rituximab and lenalidomide, zanubrutinib, rituximab and lenalidomide
- Keywords
- diffuse large B-cell lymphoma, polatuzumab vedotin, zanubrutinib, lenalidomide, rituximab, old patients, unfit, frail
- 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.
polatuzumab vedotin, zanubrutinib, rituximab and lenalidomideDrug
Drug: Polatuzumab vedotin, Zanubrutinib, Lenalidomide and Rituximab (Pola-ZR2)
Induction therapy:
The Pola-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:
Polatuzumab vedotin 1.8 mg/kg, day 2 on the 1st cycle and day 1 on the 2nd to 6th cycle; Zanubrutinib, 160 mg bid, po, day 1-21; Lenalidomide, 25 mg qd, po, day 2-11; Rituximab, 375 mg/m2, ivgtt, day 1.
Maintenance therapy:
Patients who receive complete response or partial response after induction therapy will receive lenalidomide 25 mg qd po during 1-10 days in every 21 days for 2 years.
zanubrutinib, rituximab and lenalidomideDrug
Drug: Zanubrutinib, Lenalidomide and Rituximab (ZR2)
Induction therapy:
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 1-21; Lenalidomide, 25 mg qd, po, day 2-11; Rituximab, 375 mg/m2, ivgtt, day 1.
Maintenance therapy:
Patients who receive complete response or partial response after induction therapy will receive lenalidomide 25 mg qd po during 1-10 days in every 21 days for 2 years.
| Study group | Role | What they receive |
|---|---|---|
| Pola-ZR2 | Experimental | six courses of polatuzumab vedotin, zanubrutinib, rituximab and lenalidomide induction therapy and lenalidomide maintenance therapy Receives: Drug: polatuzumab vedotin, zanubrutinib, rituximab and lenalidomide |
| ZR2 | Active comparator | six courses of zanubrutinib, rituximab and lenalidomide induction therapy and lenalidomide maintenance therapy Receives: Drug: zanubrutinib, rituximab and lenalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
2-year PFS rate
Measured: up to approximately 2 years
Secondary outcomes (9)
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)
2-year OS rate
2-year OS rate
Measured: Baseline up to data cut-off (up to approximately 2 years)
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)
Complete response rate
Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria.
Measured: End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]]
Overall response rate
Percentage of participants with complete or partial response was determined on the basis of investigator assessments according to 2014 Lugano criteria.
Measured: End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]]
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 5 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 posted26 Jul 2024
- Study start29 Jul 2024
- Primary completion10 Aug 2028 (estimated)
- Study completion10 Aug 2029 (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
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ruijin Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhao Weili, Ruijin Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06522555
- Sponsor's protocol ID
- POTENT STUDY
- Status last verified
- Aug 2024
- First submitted
- 7 Jul 2024
- Last updated
- 5 Aug 2024
- 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 5 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy and Safety of Pola-ZR2 (Polatuzumab Vedotin, Zanubrutinib, Rituximab and Lenalidomide) Versus ZR2 (Zanubrutinib, Rituximab and Lenalidomide) in the Treatment of Old Patients With de Novo Diffuse Large B-cell Lymphoma: A Multicenter, Prospective, Randomized, Open-label, Controlled Trial
- ClinicalTrials.gov ID
- NCT06522555
- Acronym / sponsor ID
- POTENT STUDY
- Conditions
- Diffuse Large B-Cell Lymphoma
- Keywords
- diffuse large B-cell lymphoma, polatuzumab vedotin, zanubrutinib, lenalidomide, rituximab, old patients, unfit, frail
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Ruijin HospitalUniversity, hospital or other
- Study start
- 29 Jul 2024 (actual)
- Primary completion
- 10 Aug 2028 (estimated)
- Study completion
- 10 Aug 2029 (estimated)
- First posted
- 26 Jul 2024 (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 Pola-ZR2 (polatuzumab vedotin, zanubrutinib, rituximab and lenalidomide) versus ZR2 (zanubrutinib, rituximab and lenalidomide) in the treatment of old patients with de novo diffuse large B-cell lymphoma
Detailed description
This study will evaluate the efficacy and safety of Pola-ZR2 versus ZR2 in the treatment of elderly de novo diffuse large B-cell lymphoma patients. Subjects will be randomly assigned 1:1 to Pola-ZR2 or ZR2 regimen. The stratification will be performed according to international prognostic index (2-3 / 4-5).
Patients in Pola-ZR2 group will receive 6 cycles of polatuzumab vedotin 1.8 mg/kg, day 2 on the 1st cycle and day 1 on the 2nd to 6th cycle, 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 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 who receive complete response or partial response after induction therapy will receive lenalidomide 25 mg qd po during 1-10 days in every 21 days for 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pola-ZR2 | Experimental | Drug: polatuzumab vedotin, zanubrutinib, rituximab and lenalidomidesix courses of polatuzumab vedotin, zanubrutinib, rituximab and lenalidomide induction therapy and lenalidomide maintenance therapy |
| ZR2 | Active comparator | Drug: zanubrutinib, rituximab and lenalidomidesix courses of zanubrutinib, rituximab and lenalidomide induction therapy and lenalidomide maintenance therapy |
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)
- Aged ≥ 80 years old or aged 70-79 with comprehensive geriatric assessment stratified as unfit or frail
- International prognostic index score 2 to 5
- 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)
- Able to swallow capsules
Key exclusion criteria (11 listed)
- Uncontrolled 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 ALT or AST is 2 times higher than the upper limits of normal (ULN), serum 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).
- uncontrollable or significant cardiovascular diseases, including but not limited to: Left ventricular ejection fraction<50% Cardiomyopathy, such as dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy QTc prolongation with clinical significance, QTc interval>470ms (females) or 480ms (males), type 2 second-degree atrioventricular block or third-degree atrioventricular block
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 |
|---|---|---|
| polatuzumab vedotin, zanubrutinib, rituximab and lenalidomideDrug: Polatuzumab vedotin, Zanubrutinib, Lenalidomide and Rituximab (Pola-ZR2) Induction therapy: The Pola-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: Polatuzumab vedotin 1.8 mg/kg, day 2 on the 1st cycle and day 1 on the 2nd to 6th cycle; Zanubrutinib, 160 mg bid, po, day 1-21; Lenalidomide, 25 mg qd, po, day 2-11; Rituximab, 375 mg/m2, ivgtt, day 1. Maintenance therapy: Patients who receive complete response or partial response after induction therapy will receive lenalidomide 25 mg qd po during 1-10 days in every 21 days for 2 years. | Drug | Pola-ZR2 |
| zanubrutinib, rituximab and lenalidomideDrug: Zanubrutinib, Lenalidomide and Rituximab (ZR2) Induction therapy: 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 1-21; Lenalidomide, 25 mg qd, po, day 2-11; Rituximab, 375 mg/m2, ivgtt, day 1. Maintenance therapy: Patients who receive complete response or partial response after induction therapy will receive lenalidomide 25 mg qd po during 1-10 days in every 21 days for 2 years. | Drug | ZR2 |
Primary outcome
2-year PFS rate
Time frame: up to approximately 2 years
9 secondary outcomes
Progression free survival
Time frame: Baseline up to data cut-off (up to approximately 2 years)
2-year OS rate
Time frame: Baseline up to data cut-off (up to approximately 2 years)
Overall survival
Time frame: Baseline up to data cut-off (up to approximately 2 years)
Complete response rate
Time frame: End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]]
Overall response rate
Time frame: End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]]
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0
Time frame: From enrollment to study completion, a maximum of 5 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
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2024.
- Individual participant dataSharing planned: No
Related trials for Diffuse Large B-Cell Lymphoma
Active, not recruitingPhase 1/2
Study of Oral MRT-2359 in Selected Cancer Patients
NSCLC, SCLC
Active, not recruitingEarly Phase 1
Iomab-ACT: A Pilot Study of 131-I Apamistamab Followed by CD19-Targeted CAR T-Cell Therapy for Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia or Diffuse Large B-Cell Lymphoma
B-ALL, DLBCL
Not yet recruitingPhase 2
The CARDIOPROTECT Trial
Diffuse Large B-cell Lymphoma (DLBCL), Cardiotoxicity
Not yet recruitingPhase 2
QLS4131 Plus Isa-V-CHOP in Newly Diagnosed, HIV-Negative PBL: A Single-Center, Single-Arm, Phase II Study
Plasmablastic Lymphoma
RecruitingPhase 2
Testing the Effectiveness of a Combination Targeted Therapy (ViPOR) for Patients With Relapsed and/or Refractory Aggressive B-cell Lymphoma
High Grade B-Cell Lymphoma With MYC and BCL6 Rearrangements, Recurrent Diffuse Large B-Cell Lymphoma
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.
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 polatuzumab vedotin, zanubrutinib, rituximab and lenalidomide and zanubrutinib, rituximab and lenalidomide 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 11 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: looking for participants now, as of the sponsor's last update on 5 Aug 2024. 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?
This study is still under way. Results are not available in the source record yet.
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?
2-year PFS rate (time frame: 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 5 Aug 2024.