Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Number of Participants With Adverse Events in Diffuse Large B-Cell Lymphoma (DLBCL) Population |
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, and Serious Adverse Events (SAEs). |
Baseline up to 5 years |
|
| Primary |
Number of Participants With Adverse Events in Non-DLBCL Population |
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, and Serious Adverse Events (SAEs). |
Baseline up to 5 years |
|
| Primary |
Number of Participants With Dose Limiting Toxicities (DLTs) in DLBCL Population |
All dose-escalation cohorts will consist of at least 3 participants. If a DLT is observed in 1 participant at a given dose level during the DLT observation period before dose escalation, additional participants will be enrolled at that dose level for a total of at least 6 participants. DLT assessment forms part of determining the Maximum Tolerated Dose (MTD). The highest dose level resulting in DLTs in less than one-third of a minimum of 6 participants will be declared the MTD. |
Cycle (Cy) 1 Day 1 (D1) to Cy 2 D1 (cycle length=21 days) |
|
| Primary |
Number of Participants With DLTs in Non-DLBCL Population |
All dose-escalation cohorts will consist of at least 3 participants. If a DLT is observed in 1 participant at a given dose level during the DLT observation period before dose escalation, additional participants will be enrolled at that dose level for a total of at least 6 participants. DLT assessment forms part of determining the Maximum Tolerated Dose (MTD). The highest dose level resulting in DLTs in less than one-third of a minimum of 6 participants will be declared the MTD. |
Cycle (Cy) 1 Day 1 (D1) to Cy 2 D1 (cycle length=21 days) |
|
| Secondary |
Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for DLBCL Population |
Complete Response (CR) rate was defined as the percentage of participants with CR at the end of treatment, as assessed by the investigator, with and without FDG-PET. The overall response rate was defined as the percentage of participants with CR or PR at the end of treatment, as assessed by the investigator, with and without FDG-PET. |
At the end of treatment (Month 6) |
|
| Secondary |
Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population |
Complete Response (CR) rate was defined as the percentage of participants with CR at the end of treatment, as assessed by the investigator, with and without FDG-PET. The overall response rate was defined as the percentage of participants with CR or PR at the end of treatment, as assessed by the investigator, with and without FDG-PET. |
At the end of treatment (Month 6) |
|
| Secondary |
Number of Participants With Anti-Polatuzumab Vedotin Antibodies |
The Anti-Drug Antibody (ADA) screening assay was optimized to tolerate drug interference and was able to detect 90 and 500 ng/mL of the positive control sample in the presence of 20 µg/mL of polatuzumab vedotin. Polatuzumab vedotin total antibody concentrations were determined for each ADA sample. Out of a total of 186 ADA samples that were measured for polatuzumab vedotin total antibody, 184 samples had levels less than 20 µg/mL. Polatuzumab vedotin total antibody concentrations ranged from <0.050 µg/mL to 52.1 µg/mL with a median concentration of 3.38 µg/mL. |
Baseline up to Month 9 (assessed prior to polatuzumab vedotin infusion [0 hour; Hr] on Day 2 [D2] of Cy 1 and 2, D1 of Cy 4, treatment completion/early termination [Month 6], and at 3 months post-treatment [Month 9]; cycle length=21 days) |
|
| Secondary |
Number of Participants With Anti-Obinutuzumab Antibodies |
The ADA screening assay was optimized to tolerate drug interference and was able to detect 500 ng/mL of the ADA-positive control sample in the presence of 50 micrograms/mL of obinutuzumab. Obinutuzumab concentrations were determined for each ADA sample. Out of a total of 48 ADA samples that were measured for obinutuzumab, 9 samples had levels less than 50 micrograms/mL of obinutuzumab. Obinutuzumab concentrations in ADA samples ranged from 0.282 micrograms/mL to 522 micrograms/mL with a median concentration of 210 micrograms/mL. Therefore, it is possible that samples with obinutuzumab concentrations greater than 50 micrograms/mL might be false negative for ADA. |
Baseline up to Month 9 (assessed prior to obinutuzumab infusion [0 Hr] on D1 of Cy 1, 2, 4 and at 3 months post-treatment [Month 9]; cycle length=21 days) |
|
| Secondary |
Area Under the Concentration-Time Curve (AUC) of Polatuzumab Vedotin |
AUC information for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis. |
Pre-polatuzumab vedotin infusion (Hr 0), 30 minutes (min) post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days) |
|
| Secondary |
Maximum Concentration (Cmax) of Polatuzumab Vedotin |
Cmax for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis. |
Pre-polatuzumab vedotin infusion (Hr 0), 30 min post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days) |
|
| Secondary |
Clearance (CL) of Polatuzumab Vedotin |
CL for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis. |
Pre-polatuzumab vedotin infusion (Hr 0), 30 min post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days) |
|
| Secondary |
Terminal Half-Life (t1/2) of Polatuzumab Vedotin |
t1/2 for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis. |
Pre-polatuzumab vedotin infusion (Hr 0), 30 min post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days) |
|
| Secondary |
Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin |
Vss for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis. |
Pre-polatuzumab vedotin infusion (Hr 0), 30 min post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days) |
|
| Secondary |
Plasma Levels of Cyclophosphamide |
Plasma levels of cyclophosphamide will be assessed and compared at the same timepoints of Cycle 1 (in the absence of polatuzumab vedotin) and Cycle 3 (in the presence of polatuzumab vedotin), and compared with historical data to evaluate potential PK interactions with polatuzumab vedotin. |
End of cyclophosphamide infusion (infusion time=1-24 Hr), 3 and 23 hours post end of cyclophosphamide infusion on D1 of Cy 1 and 3 (cycle length=21 days) |
|
| Secondary |
Plasma Levels of Doxorubicin |
Plasma levels of doxorubicin will be assessed and compared at the same timepoints of Cycle 1 (in the absence of polatuzumab vedotin) and Cycle 3 (in the presence of polatuzumab vedotin), and compared with historical data to evaluate potential PK interactions with polatuzumab vedotin. |
2, 24 hours post end of doxorubicin infusion (infusion time=15 min) on D1 of Cy 1 and 3 (cycle length=21 days) |
|
| Secondary |
Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score |
The TINAS is an 11-item questionnaire scored on a 0 to 10 scale, with 0 being the symptom is not present to 10 being the symptom is as bad as the participant can imagine. The questionnaire will be analyzed for the individual neuropathy symptoms experienced by a participant as well as the calculation of an overall neuropathy severity score. The TINAS scale will be completed daily over the course of study treatment. Additionally, to collect information about the reversibility of peripheral neuropathy, the TINAS will be completed once a week for the first 2 months, then once a month for the next 10 months following treatment completion. Results are only being reported here up until the End of Treatment visit (duration of Study treatment). |
Weekly up to Month 6 (22 weeks). TINAS data were collected daily, though for the analysis purpose for each participant, only the first record of each week was selected. |
|
| Secondary |
Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score |
The TINAS is an 11-item questionnaire scored on a 0 to 10 scale, with 0 being the symptom is not present to 10 being the symptom is as bad as the patient can imagine. The questionnaire will be analyzed for the individual neuropathy symptoms experienced by a participant as well as the calculation of an overall neuropathy severity score. The TINAS scale will be completed daily over the course of study treatment. Additionally, to collect information about the reversibility of peripheral neuropathy, the TINAS will be completed once a week for the first 2 months, then once a month for the next 10 months following treatment completion. Additionally, a single item that asks patients to rate when numbness and tingling was at the worst will be used to predict the onset of peripheral neuropathy. The measure takes less than 5 minutes to complete. Results are only being reported here up until the End of Treatment visit (duration of Study treatment). |
Weekly up to Month 6 (22 weeks). TINAS data were collected daily, though for the analysis purpose for each participant, only the first record of each week was selected. |
|
| Secondary |
Duration of Response, as Assessed by Investigator Using Cheson Criteria for DLBCL Population |
Time 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 (PFS), as assessed by the investigator for the subgroup of participants with a best overall response of CR or PR. For participants achieving a response who did not experience disease progression, relapse, or died prior to the time of the analysis, the DOR was censored on the date of last disease assessment. |
Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years) |
|
| Secondary |
Duration of Response, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population |
Time 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 (PFS), as assessed by the investigator for the subgroup of participants with a best overall response of CR or PR. For participants achieving a response who did not experience disease progression, relapse, or died prior to the time of the analysis, the DOR was censored on the date of last disease assessment. |
Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years) |
|
| Secondary |
Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population |
Time from date of first dose of study drug (Day 1) to the first occurrence of progression or relapse, or death from any cause while in the study, as assessed by the investigator. If a participant did not experience progressive disease or death, PFS was censored on the day of the last tumor assessment. If a post-baseline assessment was not available, PFS was censored on Day 1. |
Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years) |
|
| Secondary |
Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population |
Time from date of first dose of study drug (Day 1) to the first occurrence of progression or relapse, or death from any cause while in the study, as assessed by the investigator. If a participant did not experience progressive disease or death, PFS was censored on the day of the last tumor assessment. If a post-baseline assessment was not available, PFS was censored on Day 1. |
Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years) |
|
| Secondary |
Event Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population |
Time from randomization to disease progression or relapse, as assessed by the investigator, death from any cause, or initiation of any new anti-lymphoma therapy (NALT). If the specified event (disease progression or relapse, death, initiation of a NALT) did not occur, EFS was censored at the date of last tumor assessment. For participants without an event who did not have post-baseline tumor assessments, EFS was censored at the time of randomization. |
Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years) |
|
| Secondary |
Event Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population |
Time from randomization to disease progression or relapse, as assessed by the investigator, death from any cause, or initiation of any new anti-lymphoma therapy (NALT). If the specified event (disease progression or relapse, death, initiation of a NALT) did not occur, EFS was censored at the date of last tumor assessment. For participants without an event who did not have post-baseline tumor assessments, EFS was censored at the time of randomization. |
Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years) |
|
| Secondary |
Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for DLBCL Population |
Relative dose intensity (DI) was defined as the ratio of the amount of a drug actually administered (actual DI) to the amount planned (planned DI) for a fixed time period, expressed as a percentage. |
6 months |
|
| Secondary |
Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for Non-DLBCL Population |
Relative dose intensity (DI) was defined as the ratio of the amount of a drug actually administered (actual DI) to the amount planned (planned DI) for a fixed time period, expressed as a percentage. |
6 months |
|
| Secondary |
Overall Survival for DLBCL Population |
The time from the date of randomization to the date of death from any cause. For participants who did not die at the time of the analyses, OS was censored on the last date when the participants were known to be alive. |
Screening up to death due to any cause (up to approximately 6 years) |
|
| Secondary |
Overall Survival for Non-DLBCL Population |
The time from the date of randomization to the date of death from any cause. For participants who did not die at the time of the analyses, OS was censored on the last date when the participants were known to be alive. |
Screening up to death due to any cause (up to approximately 6 years) |
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