Back to resultsA Study of Polatuzumab Vedotin in Combination With Rituximab or Obinutuzumab, Cyclophosphamide, Doxorubicin, and Prednisone in Participants With B-Cell Non-Hodgkin's Lymphoma
Primary Purpose
Lymphoma, Non Hodgkin
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Cyclophosphamide
Doxorubicin
Obinutuzumab
Polatuzumab Vedotin
Prednisolone
Prednisone
Rituximab
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma, Non Hodgkin
Eligibility Criteria
Inclusion Criteria:
All Participants:
- At least one bi-dimensionally measurable lesion, defined as greater than (>) 1.5 centimeters (cm) in its longest dimension
- Life expectancy of at least 24 weeks
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Adequate hematologic function (unless inadequate function is due to underlying disease, as established by extensive bone marrow involvement or is due to hypersplenism secondary to the involvement of the spleen by lymphoma per the investigator)
- Agreement to use highly effective contraception measures. Women of childbearing potential must agree to remain abstinent or use contraceptive measures that result in a failure rate of <1 percent (%) per year during the treatment period and for at least 12 months for R-CHP arm or for at least 18 months for G-CHP arm after the last dose of study drug. Men must agree to remain abstinent or to use a condom plus an additional contraceptive method that together result in a failure rate of <1% per year during the treatment period and for at least 5 months after the last dose of study drug
Dose-Escalation Portion of the Study:
- Histologically confirmed B-cell NHL: Participants with newly diagnosed B-cell NHL or relapsed/refractory B-cell NHL are eligible
- No more than one prior systemic treatment regimen for B-cell NHL (single agent anti-cluster of differentiation [CD] 20 monoclonal antibody therapy will not be counted as a prior treatment regimen)
- No prior treatment with anthracyclines
Expansion Portion of the Study:
- Previously untreated participants with diffuse large B-cell lymphoma (DLBCL)
- International Prognostic Index (IPI) score of 2-5
Exclusion Criteria:
Dose-Escalation Portion of the Study:
- Diagnosis of primary mediastinal DLBCL
Expansion Portion of the Study:
- Participants with transformed lymphoma
- Prior therapy for NHL
All Participants:
- Prior stem cell transplant
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
- Contraindication to receive any of the individual components of R-CHP or G-CHP
- Current Grade greater than (>) 1 peripheral neuropathy
- Ongoing corticosteroid use of >30 milligrams per day (mg/day) of prednisone/prednisolone or equivalent. Participants receiving corticosteroid treatment with less than or equal to (</=) 30 mg/day of prednisone/prednisolone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration before Cycle 1 Day 1
- Primary central nervous system (CNS) lymphoma
- Vaccination with live vaccines within 6 months before Cycle 1 Day 1
- History of other malignancy that could affect compliance with the protocol or interpretation of results. Participants with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix are eligible. Participants with a malignancy that has been treated with surgery alone with curative intent will also be excluded unless the malignancy has been in documented remission without treatment for greater than or equal to (</=) 5 years before enrollment
- Evidence of significant, uncontrolled concomitant diseases, including renal disease that would preclude chemotherapy administration, or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
- Significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, congestive heart failure, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina) or significant 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 before Cycle 1 Day 1
- Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
- Positive for hepatitis B or hepatitis C infection
- Prior radiotherapy to the mediastinal/pericardial region
- Pregnant or lactating women
- Recent major surgery within 6 weeks before the start of Cycle 1 Day 1
Sites / Locations
- The University of Alabama at Birmingham
- Banner MD Anderson Cancer Center
- Washington University; Pediatrics
- Northwest Cancer Specialists
- Oregon Health and Science University
- Willamette Valley Clinical Studies; Cancer Institute
- Blue Ridge Cancer Care
- Hopital Henri Mondor, Unite Hemopathies lymphoides
- Hopital Claude Huriez - CHU Lille; Service des maladies du sang
- Centre Hospitalier Lyon Sud; Hematolgie
- Centre Henri Becquerel; Hematologie
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Polatuzumab Vedotin (1.4mg) + G-CHP
Polatuzumab Vedotin (1.0mg) + R-CHP
Polatuzumab Vedotin (1.8mg) + G-CHP
Polatuzumab Vedotin (1.4mg) + R-CHP
Polatuzumab Vedotin (1.8mg) + R-CHP
Polatuzumab Vedotin (2.4mg) + R-CHP
Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP
Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
Arm Description
Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP.
Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.
Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP.
Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.
Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.
Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.
Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.
Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP.
Outcomes
Primary Outcome Measures
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).
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).
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
Maximum Concentration (Cmax) of Polatuzumab Vedotin
Cmax for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.
Clearance (CL) of Polatuzumab Vedotin
CL for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.
Terminal Half-Life (t1/2) of Polatuzumab Vedotin
t1/2 for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.
Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin
Vss for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.
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.
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.
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).
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01992653
Brief Title
A Study of Polatuzumab Vedotin in Combination With Rituximab or Obinutuzumab, Cyclophosphamide, Doxorubicin, and Prednisone in Participants With B-Cell Non-Hodgkin's Lymphoma
Official Title
A Phase Ib/II Study Evaluating the Safety, Tolerability and Anti-Tumor Activity of Polatuzumab Vedotin (DCDS4501A) in Combination With Rituximab or Obinutuzumab, Cyclophosphamide, Doxorubicin, and Prednisone in Patients With B-Cell Non-Hodgkin's Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
November 29, 2013 (Actual)
Primary Completion Date
December 19, 2018 (Actual)
Study Completion Date
December 19, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
4. Oversight
5. Study Description
Brief Summary
This multicenter, open-label, dose-escalation study will evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of polatuzumab vedotin in combination with rituximab or obinutuzumab, cyclophosphamide, doxorubicin, and prednisone (CHP chemotherapy) in participants with non-Hodgkin's lymphoma (NHL). Participants will receive escalating doses of polatuzumab vedotin intravenously (IV) every 3 weeks in combination with standard doses of rituximab plus CHP chemotherapy (R-CHP) or obinutuzumab plus CHP chemotherapy (G-CHP). Participants will be treated for a total of six or eight cycles in accordance with local institutional practice. Two parallel treatment arms will explore doses of polatuzumab vedotin in combination with R-CHP or G-CHP. The maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of polatuzumab vedotin in combination with R-CHP will be identified before it is combined with G-CHP. Once the MTD or RP2D is determined, polatuzumab vedotin will be dosed at MTD or RP2D -1 in combination with G-CHP to start the dose escalation of this combination.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Non Hodgkin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
85 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Polatuzumab Vedotin (1.4mg) + G-CHP
Arm Type
Experimental
Arm Description
Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP.
Arm Title
Polatuzumab Vedotin (1.0mg) + R-CHP
Arm Type
Experimental
Arm Description
Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.
Arm Title
Polatuzumab Vedotin (1.8mg) + G-CHP
Arm Type
Experimental
Arm Description
Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP.
Arm Title
Polatuzumab Vedotin (1.4mg) + R-CHP
Arm Type
Experimental
Arm Description
Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.
Arm Title
Polatuzumab Vedotin (1.8mg) + R-CHP
Arm Type
Experimental
Arm Description
Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.
Arm Title
Polatuzumab Vedotin (2.4mg) + R-CHP
Arm Type
Experimental
Arm Description
Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.
Arm Title
Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP
Arm Type
Experimental
Arm Description
Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.
Arm Title
Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
Arm Type
Experimental
Arm Description
Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Cyclophosphamide will be administered at 750 milligrams per square meter (mg/m^2) IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Intervention Description
Doxorubicin will be administered at 50 mg/m^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.
Intervention Type
Drug
Intervention Name(s)
Obinutuzumab
Other Intervention Name(s)
Gazyva/Gazyvaro
Intervention Description
Obinutuzumab will be administered at 1000 milligrams (mg) IV on Cycle 1 Days 1, 8, and 15 and on Day 1 of Cycles 3-8.
Intervention Type
Drug
Intervention Name(s)
Polatuzumab Vedotin
Other Intervention Name(s)
DCDS4501A
Intervention Description
Polatuzumab vedotin will be administered at escalating doses (at a starting dose of 1 mg/kg) IV every 3 weeks, for 6 or 8 cycles.
Intervention Type
Drug
Intervention Name(s)
Prednisolone
Intervention Description
Prednisolone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Prednisone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
MabThera/Rituxan
Intervention Description
Rituximab will be administered at 375 mg/m^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events in Diffuse Large B-Cell Lymphoma (DLBCL) Population
Description
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).
Time Frame
Baseline up to 5 years
Title
Number of Participants With Adverse Events in Non-DLBCL Population
Description
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).
Time Frame
Baseline up to 5 years
Title
Number of Participants With Dose Limiting Toxicities (DLTs) in DLBCL Population
Description
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.
Time Frame
Cycle (Cy) 1 Day 1 (D1) to Cy 2 D1 (cycle length=21 days)
Title
Number of Participants With DLTs in Non-DLBCL Population
Description
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.
Time Frame
Cycle (Cy) 1 Day 1 (D1) to Cy 2 D1 (cycle length=21 days)
Secondary Outcome Measure Information:
Title
Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for DLBCL Population
Description
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.
Time Frame
At the end of treatment (Month 6)
Title
Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population
Description
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.
Time Frame
At the end of treatment (Month 6)
Title
Number of Participants With Anti-Polatuzumab Vedotin Antibodies
Description
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.
Time Frame
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)
Title
Number of Participants With Anti-Obinutuzumab Antibodies
Description
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.
Time Frame
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)
Title
Area Under the Concentration-Time Curve (AUC) of Polatuzumab Vedotin
Description
AUC information for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.
Time Frame
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)
Title
Maximum Concentration (Cmax) of Polatuzumab Vedotin
Description
Cmax for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.
Time Frame
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)
Title
Clearance (CL) of Polatuzumab Vedotin
Description
CL for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.
Time Frame
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)
Title
Terminal Half-Life (t1/2) of Polatuzumab Vedotin
Description
t1/2 for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.
Time Frame
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)
Title
Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin
Description
Vss for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.
Time Frame
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)
Title
Plasma Levels of Cyclophosphamide
Description
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.
Time Frame
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)
Title
Plasma Levels of Doxorubicin
Description
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.
Time Frame
2, 24 hours post end of doxorubicin infusion (infusion time=15 min) on D1 of Cy 1 and 3 (cycle length=21 days)
Title
Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score
Description
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).
Time Frame
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.
Title
Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score
Description
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).
Time Frame
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.
Title
Duration of Response, as Assessed by Investigator Using Cheson Criteria for DLBCL Population
Description
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.
Time Frame
Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years)
Title
Duration of Response, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population
Description
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.
Time Frame
Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years)
Title
Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population
Description
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.
Time Frame
Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years)
Title
Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population
Description
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.
Time Frame
Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years)
Title
Event Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population
Description
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.
Time Frame
Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years)
Title
Event Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population
Description
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.
Time Frame
Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years)
Title
Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for DLBCL Population
Description
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.
Time Frame
6 months
Title
Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for Non-DLBCL Population
Description
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.
Time Frame
6 months
Title
Overall Survival for DLBCL Population
Description
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.
Time Frame
Screening up to death due to any cause (up to approximately 6 years)
Title
Overall Survival for Non-DLBCL Population
Description
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.
Time Frame
Screening up to death due to any cause (up to approximately 6 years)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
All Participants:
At least one bi-dimensionally measurable lesion, defined as greater than (>) 1.5 centimeters (cm) in its longest dimension
Life expectancy of at least 24 weeks
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Adequate hematologic function (unless inadequate function is due to underlying disease, as established by extensive bone marrow involvement or is due to hypersplenism secondary to the involvement of the spleen by lymphoma per the investigator)
Agreement to use highly effective contraception measures. Women of childbearing potential must agree to remain abstinent or use contraceptive measures that result in a failure rate of <1 percent (%) per year during the treatment period and for at least 12 months for R-CHP arm or for at least 18 months for G-CHP arm after the last dose of study drug. Men must agree to remain abstinent or to use a condom plus an additional contraceptive method that together result in a failure rate of <1% per year during the treatment period and for at least 5 months after the last dose of study drug
Dose-Escalation Portion of the Study:
Histologically confirmed B-cell NHL: Participants with newly diagnosed B-cell NHL or relapsed/refractory B-cell NHL are eligible
No more than one prior systemic treatment regimen for B-cell NHL (single agent anti-cluster of differentiation [CD] 20 monoclonal antibody therapy will not be counted as a prior treatment regimen)
No prior treatment with anthracyclines
Expansion Portion of the Study:
Previously untreated participants with diffuse large B-cell lymphoma (DLBCL)
International Prognostic Index (IPI) score of 2-5
Exclusion Criteria:
Dose-Escalation Portion of the Study:
Diagnosis of primary mediastinal DLBCL
Expansion Portion of the Study:
Participants with transformed lymphoma
Prior therapy for NHL
All Participants:
Prior stem cell transplant
History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
Contraindication to receive any of the individual components of R-CHP or G-CHP
Current Grade greater than (>) 1 peripheral neuropathy
Ongoing corticosteroid use of >30 milligrams per day (mg/day) of prednisone/prednisolone or equivalent. Participants receiving corticosteroid treatment with less than or equal to (</=) 30 mg/day of prednisone/prednisolone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration before Cycle 1 Day 1
Primary central nervous system (CNS) lymphoma
Vaccination with live vaccines within 6 months before Cycle 1 Day 1
History of other malignancy that could affect compliance with the protocol or interpretation of results. Participants with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix are eligible. Participants with a malignancy that has been treated with surgery alone with curative intent will also be excluded unless the malignancy has been in documented remission without treatment for greater than or equal to (</=) 5 years before enrollment
Evidence of significant, uncontrolled concomitant diseases, including renal disease that would preclude chemotherapy administration, or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
Significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, congestive heart failure, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina) or significant 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 before Cycle 1 Day 1
Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
Positive for hepatitis B or hepatitis C infection
Prior radiotherapy to the mediastinal/pericardial region
Pregnant or lactating women
Recent major surgery within 6 weeks before the start of Cycle 1 Day 1
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Genentech, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
The University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Banner MD Anderson Cancer Center
City
Greeley
State/Province
Colorado
ZIP/Postal Code
85234
Country
United States
Facility Name
Washington University; Pediatrics
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Northwest Cancer Specialists
City
Portland
State/Province
Oregon
ZIP/Postal Code
97210
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Willamette Valley Clinical Studies; Cancer Institute
City
Springfield
State/Province
Oregon
ZIP/Postal Code
97477
Country
United States
Facility Name
Blue Ridge Cancer Care
City
Roanoke
State/Province
Virginia
ZIP/Postal Code
24014
Country
United States
Facility Name
Hopital Henri Mondor, Unite Hemopathies lymphoides
City
Creteil
ZIP/Postal Code
94010
Country
France
Facility Name
Hopital Claude Huriez - CHU Lille; Service des maladies du sang
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Centre Hospitalier Lyon Sud; Hematolgie
City
Pierre Benite
ZIP/Postal Code
69495
Country
France
Facility Name
Centre Henri Becquerel; Hematologie
City
Rouen
ZIP/Postal Code
76038
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
32770353
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.
Results Reference
derived
PubMed Identifier
31101489
Citation
Tilly H, Morschhauser F, Bartlett NL, Mehta A, Salles G, Haioun C, Munoz J, Chen AI, Kolibaba K, Lu D, Yan M, Penuel E, Hirata J, Lee C, Sharman JP. Polatuzumab vedotin in combination with immunochemotherapy in patients with previously untreated diffuse large B-cell lymphoma: an open-label, non-randomised, phase 1b-2 study. Lancet Oncol. 2019 Jul;20(7):998-1010. doi: 10.1016/S1470-2045(19)30091-9. Epub 2019 May 14.
Results Reference
derived
Learn more about this trial
A Study of Polatuzumab Vedotin in Combination With Rituximab or Obinutuzumab, Cyclophosphamide, Doxorubicin, and Prednisone in Participants With B-Cell Non-Hodgkin's Lymphoma
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