Diffuse, Large B-Cell, LymphomaPhase 3NCT04236141
A Study to Evaluate the Efficacy and Safety of Polatuzumab Vedotin in Combination With Bendamustine and Rituximab Compared With Bendamustine and Rituximab Alone in Chinese Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (R/R DLBCL).
A Phase 3 study testing Polatuzumab Vedotin, Bendamustine and Rituximab in people with Diffuse, Large B-Cell, Lymphoma, run by Hoffmann-La Roche at 10 sites in China.
Trial summary
A study to evaluate the Efficacy and Safety of Polatuzumab Vedotin in combination with BR (Bendamustine and Rituximab) compared with BR alone in Chinese participants with R/R DLBCL. Approximately 42 Chinese participants will be randomised to treatment arms in a 2:1 ratio. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse, Large B-Cell, Lymphoma
- What is being tested?
- Polatuzumab Vedotin, Bendamustine and Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 10 sitesChina
- Study dates
- 10 Jul 2020to 7 Feb 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able to comply with the study protocol and procedures, in the investigator's judgement.
- Transplant ineligible participants with R/R DLBCL.
- Confirmed DLBCL diagnosis.
- For participants who have received prior bendamustine, a response duration > 1 year (for participants who have relapsed disease after a prior regimen).
- At least one bi-dimensionally measurable lesion, defined as > 1.5 cm in its longest dimension as measured by CT or magnetic resonance imaging (MRI).
- Availability of archival or freshly collected tumor tissue before study enrolment.
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- Life expectancy of at least 24 weeks.
- ECOG Performance Status of 0, 1 or 2.
- Adequate haematologic function.
- Women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs.
- For men who are not surgically sterile: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating sperm.
- Residence in the People's Republic of China.
Who cannot join
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (MAbs) or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products.
- Contraindication to bendamustine or rituximab.
- History of sensitivity to mannitol (mannitol is an excipient in bendamustine).
- Prior use of any MAb, radioimmunoconjugate, or antibody-drug conjugate (ADC) within 5 half-lives or 4 weeks, whichever is longer, before Cycle 1, Day 1.
- Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to Cycle 1, Day 1.
- Ongoing corticosteroid use > 30 mg/day prednisone or equivalent, for purposes other than lymphoma symptom control.
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- Completion of autologous SCT within 100 days prior to Cycle 1, Day 1.
- Prior allogeneic Stem Cell Transplantation (SCT).
- Prior treatment with Chimeric Antigen Receptor (CAR) T-cell therapy.
- Eligibility for autologous SCT.
- Grade 3b Follicular Lymphoma (FL).
- History of transformation of indolent disease to DLBCL.
- Primary or secondary CNS lymphoma.
- Current Grade > 1 peripheral neuropathy.
- History of other malignancy that could affect compliance with the protocol or interpretation of results.
- Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular or pulmonary disease.
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior to Cycle 1, Day 1.
- Participants with suspected or latent tuberculosis.
- Positive Chronic Hepatitis B (HBV) infection or Hepatitis C (HCV) infection.
- Known history of HIV infection.
- Known infection human T-cell leukemia virus 1 virus.
- Vaccination with a live vaccine within 28 days prior to treatment.
- Recent major surgery (within 6 weeks before the start of Cycle 1, Day 1) other than for diagnosis.
- Pregnant or breastfeeding or intending to become pregnant during the study or within 12 months after the final dose of study treatment.
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
China10 sites
Beijing Cancer Hospital
Beijing, 100142
West China Hospital, Sichuan University
Chengdu, 610041
Sun Yet-sen University Cancer Center
Guangzhou, 510663
Harbin Medical University Cancer Hospital
Harbin, 150081
Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)
Nanjing, 210029
Jiangsu Cancer Hospital
Nanjing, 211100
Fudan University Shanghai Cancer Center
Shanghai, 200120
Union Hospital Tongji Medical College Huazhong University of Science and Technology
Wuhan, 430023
First Affiliated Hospital of Medical College of Xi'an Jiaotong University
Xi'an, 710061
Henan Cancer Hospital
Zhengzhou, 450008
About this study
Official title: A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Polatuzumab Vedotin in Combination With Bendamustine and Rituximab Compared With Bendamustine and Rituximab Alone in Chinese Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma.
A study to evaluate the Efficacy and Safety of Polatuzumab Vedotin in combination with BR (Bendamustine and Rituximab) compared with BR alone in Chinese participants with R/R DLBCL. Approximately 42 Chinese participants will be randomised to treatment arms in a 2:1 ratio. Randomisation will be conducted with the aid of an interactive web-based response system (IxRS).
- Conditions
- Diffuse, Large B-Cell, Lymphoma
- Being tested
- Polatuzumab Vedotin, Bendamustine, Rituximab, Placebo
- 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 VedotinDrug
Participants will receive a total of 6 cycles (a cycle being 21 days) of 1.8mg/kg Polatuzumab Vedotin (IV infusion) on Day 2 of Cycle 1 and Day 1 of Cycles 2-6.
BendamustineDrug
Participants will receive a total of 6 cycles (a cycle being 21 days) of 90 mg/m2 Bendamustine (IV infusion) on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6.
RituximabDrug
Participants will receive a total of 6 cycles (a cycle being 21 days) of 375 mg/m2 Rituximab (IV infusion) on Day 1 of each cycle.
PlaceboDrug
Participants will receive a total of 6 cycles (a cycle being 21 days) of Placebo (IV infusion) on Day 2 of Cycle 1 and Day 1 of Cycles 2-6.
| Study group | Role | What they receive |
|---|---|---|
| Polatuzumab Vedotin plus BR | Experimental | Not described Receives: Drug: Polatuzumab Vedotin; Drug: Bendamustine; Drug: Rituximab |
| Placebo plus BR | Active comparator | Not described Receives: Drug: Bendamustine; Drug: Rituximab; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Complete Response (CR) at the End of Treatment (EOT) Assessment Based on Positron Emission Tomography-Computed Tomography (PET-CT) Assessed by Independent Review Committee (IRC)
CR was determined by IRC according to the Lugano Response Criteria (LRC) for Malignant Lymphoma. Per LRC , CR based on PET-CT was defined as complete metabolic response (MR) in lymph nodes and extralymphatic sites with a score of 1, 2, or 3 with or without residual mass, on 5-point scale (5PS), where, 1= no uptake above background; 2 = uptake ≤ mediastinum; 3 = uptake > mediastinum but ≤ liver; 4 = uptake moderately > liver; 5 = uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment.
Measured: Up to approximately 23 weeks
Secondary outcomes (20)
Percentage of Participants With CR at the EOT Assessment Based on PET-CT as Assessed by Investigator
CR was determined by investigator according to the LRC for Malignant Lymphoma. Per LRC, CR based on PET-CT was defined as complete MR in lymph nodes and extralymphatic sites with a score of 1, 2, or 3 with or without residual mass, on 5PS, where, 1= no uptake above background; 2 = uptake ≤ mediastinum; 3 = uptake > mediastinum but ≤ liver; 4 = uptake moderately > liver; 5 = uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of FDG-avid disease in bone marrow. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment. Percentages have been rounded off to the first decimal point.
Measured: Up to approximately to 23 weeks
Percentage of Participants With Objective Response (OR) at EOT Based on PET-CT as Assessed by Investigator
OR was defined as CR or partial response (PR) at the end of treatment assessment based on PET-CT, as determined by the investigator according to the LRC. CR based on PET-CT was defined as complete MR in lymph nodes and extralymphatic sites with a score of 1, 2, or 3 with or without residual mass on 5PS, where, 1= no uptake above background; 2 = uptake ≤ mediastinum; 3 = uptake > mediastinum but ≤ liver; 4 = uptake moderately > liver; 5 = uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of FDG-avid disease in bone marrow. PR based on PET-CT was defined as partial MR in lymph nodes and extralymphatic sites with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size; no new lesions and residual uptake higher than uptake in normal bone marrow but reduced compared with baseline. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment.
Measured: Up to approximately 23 weeks
Percentage of Participants With OR at EOT Based on PET-CT as Assessed by IRC
OR was defined as CR or PR at the end of treatment assessment based on PET-CT, as determined by the IRC according to the LRC. CR based on PET-CT was defined as complete MR in lymph nodes and extralymphatic sites with a score of 1, 2, or 3 with or without residual mass on 5PS, where, 1= no uptake above background; 2 = uptake ≤ mediastinum; 3 = uptake > mediastinum but ≤ liver; 4 = uptake moderately > liver; 5 = uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of FDG-avid disease in bone marrow. PR per PET-CT was defined as partial MR in lymph nodes and extralymphatic sites with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size; no new lesions and residual uptake higher than uptake in normal marrow but reduced compared with baseline. The analysis was done 6-8 weeks after Cycle 6, Day 1(1 cycle= 21 days) or after final dose of study treatment.Percentages have been rounded off to the first decimal point.
Measured: Up to approximately 23 weeks
Percentage of Participants With CR at EOT Based on Computed Tomography (CT) as Assessed by Investigator
CR was determined by the investigator according to the LRC. Per LRC, CR based on CT was defined as complete radiologic response in lymph nodes and extralymphatic sites with target nodes/nodal masses regressing to ≤ 1.5 centimeters (cm) in longest transverse diameter (LDi) and no extralymphatic sites of disease; absence of non-measured lesion; organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, immunohistochemistry (IHC) negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment.
Measured: Up to approximately 23 weeks
Percentage of Participants With CR at EOT Based on CT as Assessed by IRC
CR was determined by the IRC according to the LRC. Per LRC, CR based on CT was defined as complete radiologic response in lymph nodes and extralymphatic sites with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no extralymphatic sites of disease; absence of non-measured lesion; organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment.
Measured: Up to approximately 23 weeks
Percentage of Participants With OR at EOT Assessment Based on CT as Assessed by Investigator
OR was defined as CR or PR, at the EOT assessment based on CT only, as determined by the investigator according to the LRC. Per LRC, CR based on CT was defined as complete radiologic response in lymph nodes and extralymphatic sites with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no extralymphatic sites of disease; absence of non-measured lesion; organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. Per LRC, PR was defined as ≥ 50% decrease in sum of the product of the perpendicular diameters (SPD) of up to 6 target nodes and extranodal sites; non-measured lesion is absent/normal, regressed, but no increase; spleen must have regressed by >50 % in length beyond normal; and no new lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment. Percentages have been rounded off to the first decimal point.
Measured: Up to approximately 23 weeks
Percentage of Participants With OR at EOT Assessment Based on CT as Assessed by IRC
OR was defined as percentage of participants with CR or PR, at EOT assessment based on CT only, as determined by IRC according to the LRC. Per LRC, CR based on CT was defined as complete radiologic response with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi. PR is ≥ 50% decrease in SPD of up to 6 target nodes and extranodal sites. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment.
Measured: Up to approximately 23 weeks
Percentage of Participants With Best Overall Response (BOR) Based on PET-CT or CT Only as Assessed by Investigator
BOR=CR/PR per PET-CT/CT by investigator per LRC.CR perPET-CT=complete MR in lymph nodes \& extralymphatic sites(ELS),score=1,2,3 with/without residual mass on5PS,1=no uptake(UT)above background;2=UT≤mediastinum;3=UT>mediastinum but ≤liver;4=UT moderately>liver;5=UT markedly higher than liver and/or new lesions; no new lesions \& FDG-avid disease absent in bone marrow.CR perCT=complete radiologic response with target nodes/nodal masses regressedto≤1.5 cm in LDi\&no ELS of disease;absence of non-measured lesion;organ enlargement regressed to normal;no new lesions;bone marrow morphology=normal,if indeterminate,IHC negative.PR per PET-CT=partial MR in lymph nodes\&ELS,score=4or5,reduced UT than baseline(BL)\&residual masses=any size;no new lesions\&residual UT >UT in normal marrow,reduced than BL.PR per CT by LCR=≥50% decrease in SPD of up to 6 target nodes \& extranodal sites;non-measured lesion=absent/normal,regressed,no increase;spleen=regressed by>50%in length beyond normal;no new lesions.
Measured: Up to every 6 months after end of treatment assessment until disease progression, study withdrawal, end of study, or death, whichever occurred first (up to approximately 82 weeks)
Percentage of Participants With Best Overall Response (BOR) Based on PET-CT or CT Only as Assessed by IRC
BOR=CR/PR per PET-CT/CT by IRC per LRC. CR per PET-CT=complete MR in lymph nodes\& ELS, score=1, 2,3 with/without residual mass on 5PS, 1=no UT above background; 2=UT≤mediastinum; 3=UT>mediastinum but ≤liver; 4=UT moderately>liver; 5=UT markedly higher than liver and/or new lesions; no new lesions \& FDG-avid disease absent in bone marrow.CR per CT=complete radiologic response with target nodes/nodal masses regressed to≤1.5 cm in LDi and no ELS of disease; absence of non-measured lesion; organ enlargement regressed to normal; no new lesions; bone marrow morphology=normal, if indeterminate, IHC negative. PR per PET-CT=partial MR in lymph nodes \& ELS, score =4 or 5,reduced UT than baseline(BL)\&residual masses=any size; no new lesions \&residual UT >UT in normal marrow, reduced than BL.PR per CT by LCR=≥50% decrease in SPD of up to 6 target nodes\& extranodal sites; non-measured lesion=absent/normal, regressed, no increase; spleen=regressed by>50% in length beyond normal; no new lesions.
Measured: Up to every 6 months after end of treatment assessment until disease progression, study withdrawal, end of study, or death, whichever occurred first (up to approximately 82 weeks)
Duration Of Response (DOR) Based on PET-CT/CT Only as Assessed by Investigator
DOR was defined as time from first occurrence of a documented objective response to disease progression, relapse or death from any cause, as determined by the investigator according to the LRC
Measured: Up to every 6 months after end of treatment assessment until disease progression, study withdrawal, end of study, or death, whichever occurred first (up to approximately 82 weeks)
DOR Based on PET-CT/CT Only as Assessed by IRC
DOR was defined as time from first occurrence of a documented objective response to disease progression, relapse or death from any cause, as determined by IRC according to the LRC.
Measured: Up to every 6 months after end of treatment assessment until disease progression, study withdrawal, end of study, or death, whichever occurred first (up to approximately 82 weeks)
Progression-Free Survival (PFS) Based on PET-CT/CT Only as Assessed by Investigator
PFS was defined as the period from date of randomization until the date of disease progression, relapse, or death from any cause based on PET-CT or CT only, as determined by the investigator according to the LRC.
Measured: Up to approximately 82 weeks
PFS Based on PET-CT/CT Only as Assessed by IRC
PFS was defined as the period from date of randomization until the date of disease progression, relapse, or death from any cause based on PET-CT or CT only, as determined by IRC according to the LRC.
Measured: Up to approximately 82 weeks
Event-Free Survival (EFS) Based on PET-CT or CT Assessed by Investigator
EFS was defined as the time from date of randomization to any treatment failure including disease progression, relapse, initiation of new anti-lymphoma treatment (NALT), or death based on PET-CT or CT only, as determined by the investigator according to the LRC.
Measured: Up to approximately 82 weeks
Overall Survival (OS)
OS was defined as the time from date of randomization until the date of death from any cause.
Measured: Up to approximately 82 weeks
Percentage of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An adverse event can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product, any new disease or exacerbation of an existing disease (a worsening in the character, frequency, or severity of a known condition), recurrence of an intermittent medical condition not present at baseline, any deterioration in a laboratory value or other clinical test that is associated with symptoms or leads to a change in study treatment or concomitant treatment or discontinuation from study drug or adverse events that are related to a protocol-mandated intervention, including those that occur prior to assignment of study treatment.
Measured: Up to approximately 82 weeks
Serum Concentration of Total Antibody at Specified Timepoints
PK of polatuzumab vedodtin-related analyte- total antibody was measured
Measured: Predose & post dose on Day 2 of Cycle 1,& post dose on Days 8 & 15 of Cycles 1& 3; predose & post dose on Day 1 of Cycles 2, 3 & 4; treatment completion/early discontinuation visit; follow-up visits at Months 3 &6 (1 cycle=21 days) up to approx. 46 weeks
Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints
PK of polatuzumab vedodtin-related analyte- acMMAE was measured.
Measured: Predose and post dose on Day 2 of Cycle 1, and post dose on Days 8 and 15 of Cycles 1 and 3; predose and post dose on Day 1 of Cycles 2, 3 and 4; treatment completion/early discontinuation visit (each cycle = 21 days) up to approximately 19 weeks
Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints
PK of polatuzumab vedodtin-related analyte- unconjugated MMAE was measured.
Measured: Predose and post dose on Day 2 of Cycle 1, and post dose on Days 8 and 15 of Cycles 1 and 3; predose and post dose on Day 1 of Cycles 2, 3 and 4; treatment completion/early discontinuation visit (each cycle = 21 days) up to approximately 19 weeks
Number of Participants With Positive Treatment Emergent Anti-Drug Antibodies (ADA) to Polatuzumab Vedotin
Treatment Emergent ADA is (a) negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result, OR (b) positive ADA result at baseline and one or more post-baseline titer results that are at least 0.60 titer unit (t.u.) greater than the baseline titer result.
Measured: Baseline up to approximately 39 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2020
- Study start10 Jul 2020
- Primary completion12 Jul 2021
- Study completion7 Feb 2022
Why it stopped: Sponsor's decision, no safety concerns
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Diffuse, Large B-Cell, LymphomaStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04236141
- Sponsor's protocol ID
- YO41543
- Status last verified
- Feb 2023
- First submitted
- 16 Jan 2020
- Last updated
- 3 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Polatuzumab Vedotin in Combination With Bendamustine and Rituximab Compared With Bendamustine and Rituximab Alone in Chinese Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma.
- ClinicalTrials.gov ID
- NCT04236141
- Acronym / sponsor ID
- YO41543
- Conditions
- Diffuse, Large B-Cell, Lymphoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor's decision, no safety concerns
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 10 Jul 2020 (actual)
- Primary completion
- 12 Jul 2021 (actual)
- Study completion
- 7 Feb 2022 (actual)
- First posted
- 22 Jan 2020 (actual)
- Results
- Posted 4 Aug 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A study to evaluate the Efficacy and Safety of Polatuzumab Vedotin in combination with BR (Bendamustine and Rituximab) compared with BR alone in Chinese participants with R/R DLBCL. Approximately 42 Chinese participants will be randomised to treatment arms in a 2:1 ratio. Randomisation will be conducted with the aid of an interactive web-based response system (IxRS).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Polatuzumab Vedotin plus BR | Experimental | Drug: Polatuzumab Vedotin, Drug: Bendamustine, Drug: Rituximab |
| Placebo plus BR | Active comparator | Drug: Bendamustine, Drug: Rituximab, Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Able to comply with the study protocol and procedures, in the investigator's judgement.
- Transplant ineligible participants with R/R DLBCL.
- Confirmed DLBCL diagnosis.
- For participants who have received prior bendamustine, a response duration > 1 year (for participants who have relapsed disease after a prior regimen).
- At least one bi-dimensionally measurable lesion, defined as > 1.5 cm in its longest dimension as measured by CT or magnetic resonance imaging (MRI).
Key exclusion criteria (25 listed)
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (MAbs) or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products.
- Contraindication to bendamustine or rituximab.
- History of sensitivity to mannitol (mannitol is an excipient in bendamustine).
- Prior use of any MAb, radioimmunoconjugate, or antibody-drug conjugate (ADC) within 5 half-lives or 4 weeks, whichever is longer, before Cycle 1, Day 1.
- Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to Cycle 1, Day 1.
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 VedotinParticipants will receive a total of 6 cycles (a cycle being 21 days) of 1.8mg/kg Polatuzumab Vedotin (IV infusion) on Day 2 of Cycle 1 and Day 1 of Cycles 2-6. | Drug | Polatuzumab Vedotin plus BR |
| BendamustineParticipants will receive a total of 6 cycles (a cycle being 21 days) of 90 mg/m2 Bendamustine (IV infusion) on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6. | Drug | Placebo plus BR, Polatuzumab Vedotin plus BR |
| RituximabParticipants will receive a total of 6 cycles (a cycle being 21 days) of 375 mg/m2 Rituximab (IV infusion) on Day 1 of each cycle. | Drug | Placebo plus BR, Polatuzumab Vedotin plus BR |
| PlaceboParticipants will receive a total of 6 cycles (a cycle being 21 days) of Placebo (IV infusion) on Day 2 of Cycle 1 and Day 1 of Cycles 2-6. | Drug | Placebo plus BR |
Primary outcome
Percentage of Participants With Complete Response (CR) at the End of Treatment (EOT) Assessment Based on Positron Emission Tomography-Computed Tomography (PET-CT) Assessed by Independent Review Committee (IRC)
Time frame: Up to approximately 23 weeks
CR was determined by IRC according to the Lugano Response Criteria (LRC) for Malignant Lymphoma. Per LRC , CR based on PET-CT was defined as complete metabolic response (MR) in lymph nodes and extralymphatic sites with a score of 1, 2, or 3 with or without residual mass, on 5-point scale (5PS), where, 1= no uptake above background; 2 = uptake ≤ mediastinum; 3 = uptake > mediastinum but ≤ liver; 4 = uptake moderately > liver; 5 = uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. The analysis was done 6-8 weeks after Cycle 6, Day 1 (1 cycle = 21 days) or after final dose of study treatment.
20 secondary outcomes
Percentage of Participants With CR at the EOT Assessment Based on PET-CT as Assessed by Investigator
Time frame: Up to approximately to 23 weeks
Percentage of Participants With Objective Response (OR) at EOT Based on PET-CT as Assessed by Investigator
Time frame: Up to approximately 23 weeks
Percentage of Participants With OR at EOT Based on PET-CT as Assessed by IRC
Time frame: Up to approximately 23 weeks
Percentage of Participants With CR at EOT Based on Computed Tomography (CT) as Assessed by Investigator
Time frame: Up to approximately 23 weeks
Percentage of Participants With CR at EOT Based on CT as Assessed by IRC
Time frame: Up to approximately 23 weeks
Percentage of Participants With OR at EOT Assessment Based on CT as Assessed by Investigator
Time frame: Up to approximately 23 weeks
Percentage of Participants With OR at EOT Assessment Based on CT as Assessed by IRC
Time frame: Up to approximately 23 weeks
Percentage of Participants With Best Overall Response (BOR) Based on PET-CT or CT Only as Assessed by Investigator
Time frame: Up to every 6 months after end of treatment assessment until disease progression, study withdrawal, end of study, or death, whichever occurred first (up to approximately 82 weeks)
Percentage of Participants With Best Overall Response (BOR) Based on PET-CT or CT Only as Assessed by IRC
Time frame: Up to every 6 months after end of treatment assessment until disease progression, study withdrawal, end of study, or death, whichever occurred first (up to approximately 82 weeks)
Duration Of Response (DOR) Based on PET-CT/CT Only as Assessed by Investigator
Time frame: Up to every 6 months after end of treatment assessment until disease progression, study withdrawal, end of study, or death, whichever occurred first (up to approximately 82 weeks)
DOR Based on PET-CT/CT Only as Assessed by IRC
Time frame: Up to every 6 months after end of treatment assessment until disease progression, study withdrawal, end of study, or death, whichever occurred first (up to approximately 82 weeks)
Progression-Free Survival (PFS) Based on PET-CT/CT Only as Assessed by Investigator
Time frame: Up to approximately 82 weeks
PFS Based on PET-CT/CT Only as Assessed by IRC
Time frame: Up to approximately 82 weeks
Event-Free Survival (EFS) Based on PET-CT or CT Assessed by Investigator
Time frame: Up to approximately 82 weeks
Overall Survival (OS)
Time frame: Up to approximately 82 weeks
Percentage of Participants With Adverse Events (AEs)
Time frame: Up to approximately 82 weeks
Serum Concentration of Total Antibody at Specified Timepoints
Time frame: Predose & post dose on Day 2 of Cycle 1,& post dose on Days 8 & 15 of Cycles 1& 3; predose & post dose on Day 1 of Cycles 2, 3 & 4; treatment completion/early discontinuation visit; follow-up visits at Months 3 &6 (1 cycle=21 days) up to approx. 46 weeks
Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints
Time frame: Predose and post dose on Day 2 of Cycle 1, and post dose on Days 8 and 15 of Cycles 1 and 3; predose and post dose on Day 1 of Cycles 2, 3 and 4; treatment completion/early discontinuation visit (each cycle = 21 days) up to approximately 19 weeks
Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints
Time frame: Predose and post dose on Day 2 of Cycle 1, and post dose on Days 8 and 15 of Cycles 1 and 3; predose and post dose on Day 1 of Cycles 2, 3 and 4; treatment completion/early discontinuation visit (each cycle = 21 days) up to approximately 19 weeks
Number of Participants With Positive Treatment Emergent Anti-Drug Antibodies (ADA) to Polatuzumab Vedotin
Time frame: Baseline up to approximately 39 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
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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.
Clinical Trials study director
Hoffmann-La Roche
10 sites 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, Bendamustine and Rituximab in people with Diffuse, Large B-Cell, Lymphoma, run by Hoffmann-La Roche at 10 sites 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 12 inclusion and 25 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: stopped early, as of the sponsor's last update on 3 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites 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?
Yes. Results are posted in the registry (first posted 4 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Complete Response (CR) at the End of Treatment (EOT) Assessment Based on Positron Emission Tomography-Computed Tomography (PET-CT) Assessed by Independent Review Committee (IRC) (time frame: Up to approximately 23 weeks). 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 3 Mar 2023; AzTrials last refreshed its copy on 8 Nov 2026.