Clinical trial NCT02257567: A Study of Polatuzumab Vedotin (DCDS4501A) in Combination With Rituximab or Obinutuzumab Plus Bendamustine in Participants With Relapsed or Refractory Follicular or Diffuse Large B-Cell Lymphoma
Official title: A Phase IB/II Study Evaluating The Safety, Tolerability and Anti-Tumor Activity of Polatuzumab Vedotin in Combination With Rituximab (R) or Obinutuzumab (G) Plus Bendamustine (B) in Relapsed or Refractory Follicular or Diffuse Large B-Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lymphoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2014-10-06
Enrollment: 331
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a multicenter, open-label study of polatuzumab vedotin administered by intravenous (IV) infusion in combination with standard doses of bendamustine (B) and rituximab (R) or obinutuzumab (G) in participants with relapsed or refractory follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL). The study comprises two stages: a Phase Ib safety run-in stage and a Phase II stage. The anticipated time on treatment is 18 weeks for participants with DLBCL and 24 weeks for participants with FL.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed relapsed or refractory FL (Grades 1, 2, or 3a) or relapsed or refractory DLBCL
* If the participant has received prior bendamustine, response duration must have been greater than (\>) 1 year (for participants who have relapse disease after a prior regimen)
* At least one bi-dimensionally measurable lesion on imaging scan defined as \>1.5 centimeters (cm) in its longest dimension
* Confirmed availability of archival or freshly collected tumor tissue
* The Phase II NF Cohorts (Arms G and H) will be required to submit tissue and pathology report for central pathology review.
* Life expectancy of at least 24 weeks
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
* Adequate hematological function unless inadequate function is due to underlying disease

Exclusion Criteria:

* 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, rituximab, or obinutuzumab
* Prior use of any MAb, radioimmunoconjugate, or antibody-drug conjugate (ADC) within 4 weeks or 5 half-lives 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 per day prednisone or equivalent, for purposes other than lymphoma symptom control
* Completion of autologous stem cell transplant (SCT) within 100 days prior to Cycle 1 Day 1
* Prior allogeneic SCT
* Eligibility for autologous SCT
* Grade 3b FL
* History of transformation of indolent disease to DLBCL
* Primary or secondary CNS lymphoma
* Current Grade \>1 peripheral neuropathy
* Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or significant pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
* 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 within 4 weeks prior to Cycle 1 Day 1
* Suspected or latent tuberculosis
* Positive test results for chronic hepatitis B virus (HBV) infection or for hepatitis C virus (HCV) antibody
* Known history of human immunodeficiency virus (HIV) seropositive status or known infection with human T-cell leukemia virus 1 (HTLV-1) virus
* Women who are pregnant or lactating or who intend to become pregnant within a year of the last dose of study treatment in the rituximab cohort or within 18 months of last dose in the obinutuzumab cohort
* Evidence of laboratory abnormalities in standard renal, hepatic, or coagulation function tests
* Treatment with chimeric antigen receptor T-cell therapy within 100 days prior to Cycle 1, Day 1

Primary outcomes:
measure: Phase Ib: Percentage of Participants With Adverse Events (AEs)
timeFrame: From the study start up to the end of the study (up to approximately 84 months)
measure: Arm G+H (Phase II NF Cohort): Percentage of Participants With AEs
timeFrame: From Month 37 to Month 84 (up to approximately 47 months)
measure: Cohort 1a (Phase Ib): Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin
timeFrame: Baseline up to approximately Month 24
measure: Cohort 1b (Phase Ib): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab
timeFrame: Baseline up to approximately Month 24
measure: Arms G+H: (Phase II NF Cohorts): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin (Lyophilized)
timeFrame: From Month 37 to Month 84 (up to approximately 47 months)
measure: Phase II Randomized and NF Cohorts: Percentage of Participants With Complete Response (CR) at Primary Response Assessment (PRA) Based on Positron Emission Tomography (PET)-Computed Tomography (CT) Scan as Determined by Independent Review Committee (IRC)
timeFrame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
measure: Arm H (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC
timeFrame: 6-8 weeks after Cycle 6, Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
measure: Arm G (Phase II NF Cohort): Area Under Concentration-Time Curve (AUC) of Polatuzumab Vedotin (Lyophilized)
timeFrame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (each cycle is 21 days DLBCL cohorts) up to approximately 9 weeks
measure: Arm G (Phase II NF Cohort): Maximum Concentration (Cmax) of Polatuzumab Vedotin (Lyophilized)
timeFrame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4,(cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
measure: Arm G (Phase II NF Cohort): Systemic Clearance (CL) of Polatuzumab Vedotin (Lyophilized)
timeFrame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
measure: Arm G (Phase II NF Cohort): Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin (Lyophilized)
timeFrame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, Day (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
Secondary outcomes:
measure: Phase II: Percentage of Participants With AEs
timeFrame: From the study start up to the end of the study (up to approximately 84 months)
measure: Arms A and C (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin
timeFrame: Baseline to approximately Month 24
measure: Arms E and F (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab
timeFrame: Baseline to approximately Month 24
measure: Phase II: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator
timeFrame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
measure: Phase II Expansion Cohorts and Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC
timeFrame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
measure: Phase II: Percentage of Participants With Objective Response (OR) at PRA Based on PET-CT as Determined by Investigator
timeFrame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
measure: Phase II: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC
timeFrame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
measure: Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator
timeFrame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
measure: Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC
timeFrame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
measure: Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator
timeFrame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
measure: Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC
timeFrame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
measure: Phase II: Percentage of Participants With Best Objective Response (BOR) Based on PET-CT or CT Only as Determined by the Investigator
timeFrame: Up to every 6 months until disease progression, withdrawal or study completion (up to approximately 84 months)
measure: DLBCL Cohorts: Percentage of Participants With BOR Based PET-CT or CT Only as Determined by IRC
timeFrame: Up to every 6 months until disease progression, withdrawal or study completion (up to approximately 84 months)
measure: DLBCL Cohorts: Duration of Response (DOR) Based on PET-CT or CT Only as Determined by the Investigator
timeFrame: From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (up to approximately 84 months)
measure: DLBCL Cohorts: DOR Based on PET-CT or CT Only as Determined by the IRC
timeFrame: From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (up to approximately 84 months)
measure: DLBCL Cohorts: Progression Free Survival (PFS) Based on PET-CT or CT Only as Determined by the Investigator
timeFrame: From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (up to approximately 84 months)
measure: DLBCL Cohorts: PFS Based on PET-CT or CT Only as Determined by the IRC
timeFrame: From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (up to approximately 84 months)
measure: Phase II NF Cohort: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator
timeFrame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
measure: Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by Investigator
timeFrame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
measure: Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC
timeFrame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
measure: Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the Investigator
timeFrame: Up to every 6 months until disease progression, withdrawal or study completion (from Month 37 to Month 84 [up to approximately 47 months])
measure: Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the IRC
timeFrame: Up to every 6 months until disease progression, withdrawal or study completion (from Month 37 to Month 84 [up to approximately 47 months])
measure: Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the Investigator
timeFrame: From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (from Month 37 to Month 84 [up to approximately 47 months])
measure: Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the IRC
timeFrame: From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (from Month 37 to Month 84 [up to approximately 47 months])
measure: Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the Investigator
timeFrame: From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (from Month 37 to Month 84 [up to approximately 47 months])
measure: Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the IRC
timeFrame: From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (from Month 37 to Month 84 [up to approximately 47 months])
measure: Phase II NF Cohort: Event-Free Survival (EFS) Based on PET-CT or CT Only, as Determined by the Investigator
timeFrame: From Month 37 to Month 84 (up to approximately 47 months)
measure: Phase II NF Cohorts: Overall Survival (OS)
timeFrame: From Month 37 to Month 84 (up to approximately 47 months)
measure: Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC
timeFrame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
measure: Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator
timeFrame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
measure: Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC
timeFrame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
measure: Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator
timeFrame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to 23 weeks)
measure: Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC
timeFrame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to 23 weeks)
measure: Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE
timeFrame: Cycle 1 Day 2: pre-dose and 30 minutes (min) post dose; Cycle 1 Days 8 and 15; Cycle 2 and 4 Day 1: pre-dose and 30 min post dose; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)
measure: Arm G+H (Phase II NF Cohorts): Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE
timeFrame: Cycle 1 Day 2: post dose; Cycle 2 and 4 Day 1: pre-dose and post dose
measure: Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab
timeFrame: Cycle 1 Days 2: pre-dose & 30 min post dose; Cycle 1 Days 8 & 15; Cycle 2 and 4 Day 1 and unscheduled visits: pre-dose & 30 min post dose; Follow up at Day 1: Months 3, 6, 12, 18 & 24; study treatment completion visit (up to approx. 84 months)
measure: Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Total Ab
timeFrame: Cycle 1 Day 2: post dose; Cycle 2 and 4 Day 1: pre-dose and post dose
measure: Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE
timeFrame: Cycle 1 Day 2: pre-dose and 30 min post dose, Cycle 1 Days 8 and 15; Cycles 2 and 4: pre-dose and 30 min post dose; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)
measure: Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE
timeFrame: Cycle 1 Day 2: post dose; Cycle 1 and 3 Day 8 and 15; Cycle 2, 3 and 4 Day 1: pre-dose and post dose
measure: Plasma Concentration of Bendamustine
timeFrame: Cycle 1 Day 2: pre-dose, 5 min, 1 hour (h); 2h, 3h and 4h post dose
measure: Serum Concentration of Rituximab
timeFrame: Cycle 1 Days 1: pre-dose and 30 min post dose; Cycle 2 and 4 Day 1: pre-dose; unscheduled visits: pre-dose and 30 min post dose (up to approximately 84 months)
measure: Serum Concentration of Obinutuzumab
timeFrame: Cycles 1 and 4 Days 1: pre-dose and 30 min post dose; Cycle 2 Day1: pre-dose; Follow up visits on Day 1: Months 3, 6, 12, 18 and 24; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)
measure: Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a
timeFrame: Cycles 1, 2 and 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
measure: Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b
timeFrame: Cycles 1, 2 and 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
measure: Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C
timeFrame: Cycle 1; Cycle 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
measure: Phase II: Cmax of Bendamustine and Rituximab in Arms B and D
timeFrame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
measure: Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F
timeFrame: Cycle 1; Cycle 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
measure: Arm H (Phase II NF Cohort): Cmax of Polatuzumab Vedotin (Lyophilized)
timeFrame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4,(cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
measure: Phase Ib: AUC From Time Zero to Infinity (AUCinf) of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a
timeFrame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
measure: Phase Ib: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b
timeFrame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
measure: Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C
timeFrame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
measure: Phase II: AUCinf of Bendamustine and Rituximab in Arms B and D
timeFrame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
measure: Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Arms E and F
timeFrame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
measure: Arm H (Phase II NF Cohort): AUC of Polatuzumab Vedotin (Lyophilized)
timeFrame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (each cycle is 21 days DLBCL cohorts) up to approximately 9 weeks
measure: Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a
timeFrame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
measure: Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b
timeFrame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
measure: Phase II: CL of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C
timeFrame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
measure: Phase II: CL of Bendamustine and Rituximab in Arms B and D
timeFrame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
measure: Phase II: CL of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F
timeFrame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
measure: Arm H (Phase II NF Cohort): CL of Polatuzumab Vedotin (Lyophilized)
timeFrame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
measure: Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1a
timeFrame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
measure: Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b
timeFrame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
measure: Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C
timeFrame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
measure: Phase II: Vss of Bendamustine and Rituximab in Arms B and D
timeFrame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
measure: Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F
timeFrame: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
measure: Arm H (Phase II NF Cohort): Vss of Polatuzumab Vedotin (Lyophilized)
timeFrame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, Day (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
measure: Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F
timeFrame: Every week during treatment (up to 24 weeks) and for the first 2 months after treatment, thereafter every month for 10 months or until withdrawal (up to 18 months overall)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Huntsville
country: United States
facility: Clearview Cancer Institute
state: Alabama
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Aurora
country: United States
facility: Univ of Colorado Canc Ctr
state: Colorado
city: Jacksonville
country: United States
facility: Cancer Specialists; North Florida ;Jacksonville (AC Skinner Pkwy)
state: Florida
city: Atlanta
country: United States
facility: Emory Univ Winship Cancer Inst
state: Georgia
city: Joliet
country: United States
facility: Joliet Oncology-Hematology; Associates, Ltd.
state: Illinois
city: Lafayette
country: United States
facility: Horizon Oncology Research, Inc.
state: Indiana
city: Baltimore
country: United States
facility: Weinberg CA Inst Franklin Sq
state: Maryland
city: Morristown
country: United States
facility: Regional Cancer Care Associates LLC - Morristown
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Germantown
country: United States
facility: West Clinic
state: Tennessee
city: Seattle
country: United States
facility: Swedish Cancer Inst.
state: Washington
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
city: Randwick
country: Australia
facility: Prince of Wales Hospital; Oncology
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Kurralta Park
country: Australia
facility: Adelaide Cancer Centre
state: South Australia
city: Clayton
country: Australia
facility: Monash Medical Centre; Haematology Research
state: Victoria
city: Vancouver
country: Canada
facility: BCCA-Vancouver Cancer Centre
state: British Columbia
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre; Oncology
state: Nova Scotia
city: Montreal
country: Canada
facility: Hopital Maisonneuve- Rosemont; Oncology
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno; Interni hematologicka a onkologicka klinika
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Ostrava
country: Czechia
facility: Fakultní nemocnice Ostrava Klinika hematoonkologie
city: Prague 2
country: Czechia
facility: I Interni klinika; Vseobecna fakultni nemocnice
city: Dijon
country: France
facility: Chu Site Du Bocage;Hematologie Clinique
city: La Roche Sur Yon
country: France
facility: Centre Hospitalier Departemental Les Oudairies
city: Lyon
country: France
facility: Centre Leon Berard; Departement Oncologie Medicale
city: Montpellier
country: France
facility: CHU Saint Eloi; Service d'Hématologie Clinique
city: Pierre Benite
country: France
facility: CHU Lyon Sud - Service Hématologie
city: Rouen
country: France
facility: Centre Henri Becquerel; Hematologie
city: Erfurt
country: Germany
facility: HELIOS Klinikum Erfurt - Innere Medizin - 4. Medizinische Klinik, Hämatologie
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Abt. für Hämatologie und Onkologie
city: Minden
country: Germany
facility: Joh. Wesling Klinikum Minden; Klinik fuer Hämatologie und Onkologie
city: Münster
country: Germany
facility: Gemeinschaftspraxis für Hämatologie und Onkologie
city: Regensburg
country: Germany
facility: Klinik der Uni Regensburg; Hämatologie/Onkologie, Studienzentrale
city: Budapest
country: Hungary
facility: Semmelweis University, First Dept of Medicine
city: Budapest
country: Hungary
facility: National Institute of Oncology, A Dept of Internal Medicine
city: Debrecen
country: Hungary
facility: University of Debrecen Medical and Health Science Center, Institute of Internal medicine Building B
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Irccs Fondazione g. Pascale;s.c. Ematologia Oncologica
state: Campania
city: Brescia
country: Italy
facility: A.O. Spedali Civili Di Brescia-P.O. Spedali Civili;U.O. Ematologia
state: Lombardia
city: Milano
country: Italy
facility: Irccs Istituto Europeo Di Oncologia (IEO); Emato-Oncologia
state: Lombardia
city: Alessandria
country: Italy
facility: Ospedale Civile SS. Antonio E Biagio DI Alessandria; Ematologia
state: Piemonte
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Nijmegen
country: Netherlands
facility: UMC St. Radboud; Hematology
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron; Servicio de Hematologia
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona; Hematology
city: Madrid
country: Spain
facility: Hospital Universitario la Paz; Servicio de Hematologia
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca;Servicio de Hematologia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio; Servicio de Hematologia
city: Ankara
country: Turkey
facility: Ankara University; Hematology
city: Izmir
country: Turkey
facility: Dokuz Eylul Uni ; Hematology
city: Samsun
country: Turkey
facility: Ondokuzmayis University Medical Faculty Heamatology Department
city: Trabzon
country: Turkey
facility: Karadeniz Technical Uni School of Medicine; Hematology
city: London
country: United Kingdom
facility: KINGS COLLEGE HOSPITAL; Commercial R&D Amendments, Kings Health Partners Clinical Trials Office
city: Manchester
country: United Kingdom
facility: Christie Hospital Nhs Trust; Medical Oncology
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital; Dept of Haematology
city: Southampton
country: United Kingdom
facility: Southampton General Hospital; Somers Cancer Research Building
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Herrera AF, Tracy S, Croft B, Opat S, Ray J, Lovejoy AF, Musick L, Paulson JN, Sehn LH, Jiang Y. Risk profiling of patients with relapsed/refractory diffuse large B-cell lymphoma by measuring circulating tumor DNA. Blood Adv. 2022 Mar 22;6(6):1651-1660. doi: 10.1182/bloodadvances.2021006415.
citation: Sehn LH, Hertzberg M, Opat S, Herrera AF, Assouline S, Flowers CR, Kim TM, McMillan A, Ozcan M, Safar V, Salles G, Ku G, Hirata J, Chang YM, Musick L, Matasar MJ. Polatuzumab vedotin plus bendamustine and rituximab in relapsed/refractory DLBCL: survival update and new extension cohort data. Blood Adv. 2022 Jan 25;6(2):533-543. doi: 10.1182/bloodadvances.2021005794.
citation: Betts KA, Thuresson PO, Felizzi F, Du EX, Dieye I, Li J, Schulz M, Masaquel AS. US cost-effectiveness of polatuzumab vedotin, bendamustine and rituximab in diffuse large B-cell lymphoma. J Comp Eff Res. 2020 Oct;9(14):1003-1015. doi: 10.2217/cer-2020-0057. Epub 2020 Oct 8.
citation: Shi R, Lu T, Ku G, Ding H, Saito T, Gibiansky L, Agarwal P, Li X, Jin JY, Girish S, Miles D, Li C, Lu D. Asian race and origin have no clinically meaningful effects on polatuzumab vedotin pharmacokinetics in patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Cancer Chemother Pharmacol. 2020 Sep;86(3):347-359. doi: 10.1007/s00280-020-04119-8. Epub 2020 Aug 8.
citation: Lu T, Gibiansky L, Li X, Li C, Shi R, Agarwal P, Hirata J, Miles D, Chanu P, Girish S, Jin JY, Lu D. Exposure-safety and exposure-efficacy analyses of polatuzumab vedotin in patients with relapsed or refractory diffuse large B-cell lymphoma. Leuk Lymphoma. 2020 Dec;61(12):2905-2914. doi: 10.1080/10428194.2020.1795154. Epub 2020 Jul 24.
citation: Sehn LH, Herrera AF, Flowers CR, Kamdar MK, McMillan A, Hertzberg M, Assouline S, Kim TM, Kim WS, Ozcan M, Hirata J, Penuel E, Paulson JN, Cheng J, Ku G, Matasar MJ. Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2020 Jan 10;38(2):155-165. doi: 10.1200/JCO.19.00172. Epub 2019 Nov 6.