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).

Browse trials for

• Lymphoma 5,578
• Lymphoma, Large B-Cell, Diffuse 1,390

Lymphoma

5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.

This study's enrollment of 42 is close to the median of 40 across 4,508 interventional studies indexed under Lymphoma.

Lead sponsor

Hoffmann-La Roche is the lead sponsor of 2,061 studies on the registry; 85 are open to participants now.

Of its 319 completed or terminated interventional studies of FDA-regulated products, 239 (75%) have results posted.

Study arms

• Experimental
  Polatuzumab Vedotin plus BR

  Drug: Polatuzumab Vedotin · Drug: Bendamustine · Drug: Rituximab

• Active comparator
  Placebo plus BR

  Drug: Bendamustine · Drug: Rituximab · Drug: Placebo

Interventions

• DrugPolatuzumab Vedotin

  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.

• DrugBendamustine

  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.

• DrugRituximab

  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.

• DrugPlacebo

  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.

Primary outcomes

1. 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.

   Time frame: Up to approximately 23 weeks

Secondary outcomes

1. 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.

   Time frame: Up to approximately to 23 weeks

2. 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.

   Time frame: Up to approximately 23 weeks

3. 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.

   Time frame: Up to approximately 23 weeks

4. 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.

   Time frame: Up to approximately 23 weeks

5. 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.

   Time frame: Up to approximately 23 weeks

6. 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.

   Time frame: Up to approximately 23 weeks

7. 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.

   Time frame: Up to approximately 23 weeks

8. 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.

   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)

9. 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.

   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)

10. 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

    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)

11. 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.

    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)

12. 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.

    Time frame: Up to approximately 82 weeks

13. 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.

    Time frame: Up to approximately 82 weeks

14. 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.

    Time frame: Up to approximately 82 weeks

15. Overall Survival (OS)

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

    Time frame: Up to approximately 82 weeks

16. 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.

    Time frame: Up to approximately 82 weeks

17. Serum Concentration of Total Antibody at Specified Timepoints

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

    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

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

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

    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

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

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

    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

20. 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.

    Time frame: Baseline up to approximately 39 weeks

Baseline characteristics

Study documents

• Study protocol · May 12, 2020
• Statistical analysis plan · Mar 8, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: 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).