Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Bendamustine Hydrochloride

Rituximab

Polatuzumab vedotin

Antineoplastic Agents, Immunological

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunoconjugates

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.

Polatuzumab Vedotin

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.

Bendamustine

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.

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.

Placebo

Clinical Trials

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).

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 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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

OS was defined as the time from date of randomization until the date of death from any cause.

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.

PK of polatuzumab vedodtin-related analyte- total antibody was measured

PK of polatuzumab vedodtin-related analyte- acMMAE was measured.

PK of polatuzumab vedodtin-related analyte- unconjugated MMAE was measured.

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.

Hoffmann-La Roche

All-cause mortality is reported for all enrolled participants. Serious and other adverse events are reported for safety population which included all participants who received at least 1 dose of study drug.

Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days

Polatuzumab Vedotin Plus Bendamustine and Rituximab

Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6. Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.

Placebo Plus Bendamustine and Rituximab

Participants received polatuzumab vedotin administered at an initial dose of 1.8 mg/kg, as IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6.

Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.

Participants received polatuzumab vedotin matching placebo by IV infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6.

Participants also received bendamustine, 90 mg/m\^2, as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with placebo. Each cycle is 21 days.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

ITT population included all participants randomized, whether or not the participants received the assigned treatment.

Medical Communications

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)

Percentage of Participants With CR at the EOT Assessment Based on PET-CT as Assessed by Investigator

Percentage of Participants With Objective Response (OR) at EOT Based on PET-CT as Assessed by Investigator

Percentage of Participants With OR at EOT Based on PET-CT as Assessed by IRC

Percentage of Participants With CR at EOT Based on Computed Tomography (CT) as Assessed by Investigator

Percentage of Participants With CR at EOT Based on CT as Assessed by IRC

Percentage of Participants With OR at EOT Assessment Based on CT as Assessed by Investigator

Percentage of Participants With OR at EOT Assessment Based on CT as Assessed by IRC

Percentage of Participants With Best Overall Response (BOR) Based on PET-CT or CT Only as Assessed by Investigator

Percentage of Participants With Best Overall Response (BOR) Based on PET-CT or CT Only as Assessed by IRC

ITT population included all participants randomized, whether or not the participants received the assigned treatment. Overall number of participants analyzed are the number of BOR responders as assessed by investigator.

Duration Of Response (DOR) Based on PET-CT/CT Only as Assessed by Investigator

ITT population included all participants randomized, whether or not the participants received the assigned treatment. Overall number of participants analyzed are the number of BOR responders assessed by IRC.

DOR Based on PET-CT/CT Only as Assessed by IRC

Progression-Free Survival (PFS) Based on PET-CT/CT Only as Assessed by Investigator

PFS Based on PET-CT/CT Only as Assessed by IRC

Event-Free Survival (EFS) Based on PET-CT or CT Assessed by Investigator

Overall Survival (OS)

Safety population included all randomized participants who received at least one dose of the study drug.

Percentage of Participants With Adverse Events (AEs)

Cycle 1 Day 2: Pre-dose

Cycle 1 Day 2: Post dose

Cycle 1 Day 8 Post dose

Cycle 1 Day 15 Post dose

Cycle 2 Day 1: Pre-dose

Cycle 2 Day 1: Post dose

Cycle 3 Day 1: Pre-dose

Cycle 3 Day 1: Post dose

Cycle 3 Day 8 Post dose

Cycle 3 Day 15 Post dose

Cycle 4 Day 1: Pre-dose

Cycle 4 Day 1: Post dose

Treatment completion/Early discontinuation

Follow-Up Month 3

Follow-Up Month 6

PK-evaluable population included all participants who had at least one evaluable PK sample post dose for at least one analyte. Number analyzed is the number of participants with data available for analysis at the specified time point.

Serum Concentration of Total Antibody at Specified Timepoints

Plasma Concentration of Antibody-Conjugated Monomethyl Auristatin E (acMMAE) at Specified Timepoints

Plasma Concentration of Unconjugated Monomethyl Auristatin E (MMAE) at Specified Timepoints

Immunogenicity-evaluable population (Post-Baseline Evaluable) included all participants with at least one evaluable post-baseline anti-drug antibody (ADA) sample.

Number of Participants With Positive Treatment Emergent Anti-Drug Antibodies (ADA) to Polatuzumab Vedotin

Participants received polatuzumab vedotin administered at an initial dose of 1.8 milligrams per kilogram (mg/kg), as intravenous (IV) infusion on Day 2 of Cycle 1 and thereafter on Day 1 of Cycles 2-6.

Participants also received bendamustine, 90 milligrams per square meter (mg/m\^2), as IV infusion, on Days 2 and 3 of Cycle 1 and thereafter on Days 1 and 2 of Cycles 2-6 and rituximab, 375 mg/m\^2, as IV infusion, at least 30 minutes before the administration of other study treatments, on Day 1 of Cycles 1-6, concurrently with polatuzumab vedotin. Each cycle is 21 days.

Spots Global Cancer Trial Database for 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).

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial