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A Study of Polatuzumab Vedotin in Combination With Rituximab or Obinutuzumab, Cyclophosphamide, Doxorubicin, and Prednisone in Participants With B-Cell Non-Hodgkin's Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01992653
Recruitment Status : Completed
First Posted : November 25, 2013
Results First Posted : March 3, 2020
Last Update Posted : March 3, 2020
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Tracking Information
First Submitted Date  ICMJE October 28, 2013
First Posted Date  ICMJE November 25, 2013
Results First Submitted Date  ICMJE December 18, 2019
Results First Posted Date  ICMJE March 3, 2020
Last Update Posted Date March 3, 2020
Actual Study Start Date  ICMJE November 29, 2013
Actual Primary Completion Date December 19, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 18, 2020)
  • Number of Participants With Adverse Events in Diffuse Large B-Cell Lymphoma (DLBCL) Population [ Time Frame: Baseline up to 5 years ]
    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 [ Time Frame: Baseline up to 5 years ]
    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 [ Time Frame: Cycle (Cy) 1 Day 1 (D1) to Cy 2 D1 (cycle length=21 days) ]
    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 [ Time Frame: Cycle (Cy) 1 Day 1 (D1) to Cy 2 D1 (cycle length=21 days) ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 19, 2013)
  • Safety: Incidence of adverse events [ Time Frame: up to approximately 40 weeks ]
  • Safety: Incidence of anti-DCDS4501A antibodies [ Time Frame: 24 weeks ]
  • Dose-limiting toxicities [ Time Frame: 21 days ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 18, 2020)
  • Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for DLBCL Population [ Time Frame: At the end of treatment (Month 6) ]
    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 [ Time Frame: At the end of treatment (Month 6) ]
    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 [ 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) ]
    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 [ 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) ]
    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 [ 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) ]
    AUC information for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.
  • Maximum Concentration (Cmax) of Polatuzumab Vedotin [ 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) ]
    Cmax for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.
  • Clearance (CL) of Polatuzumab Vedotin [ 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) ]
    CL for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.
  • Terminal Half-Life (t1/2) of Polatuzumab Vedotin [ 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) ]
    t1/2 for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.
  • Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin [ 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) ]
    Vss for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.
  • Plasma Levels of Cyclophosphamide [ 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) ]
    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 [ 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) ]
    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 [ 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. ]
    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 [ 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. ]
    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 Frame: Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years) ]
    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 Frame: Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years) ]
    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 Frame: Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years) ]
    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 Frame: Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years) ]
    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 Frame: Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years) ]
    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 Frame: Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years) ]
    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 [ Time Frame: 6 months ]
    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 [ Time Frame: 6 months ]
    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 [ Time Frame: Screening up to death due to any cause (up to approximately 6 years) ]
    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 [ Time Frame: Screening up to death due to any cause (up to approximately 6 years) ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 19, 2013)
  • Pharmacokinetics: Area under the concentration-time curve [ Time Frame: Participants will be followed through four cycles of treatment, for an expected average of 12 weeks. ]
  • Pharmacokinetics: Maximum concentration (Cmax) [ Time Frame: Participants will be followed through four cycles of treatment, for an expected average of 12 weeks. ]
  • Pharmacokinetics: Clearance (CL) [ Time Frame: Participants will be followed through four cycles of treatment, for an expected average of 12 weeks. ]
  • Pharmacokinetics: Terminal half-life (t1/2) [ Time Frame: Participants will be followed through four cycles of treatment, for an expected average of 12 weeks. ]
  • Pharmacokinetics: Steady-state volume of distribution (Vss) [ Time Frame: Participants will be followed through four cycles of treatment, for an expected average of 12 weeks. ]
  • Objective response rate [ Time Frame: 24 weeks ]
  • Complete response rate [ Time Frame: 24 weeks ]
  • Duration of response [ Time Frame: approximately 2.5 years ]
  • Progression-free survival [ Time Frame: approximately 2.5 years ]
  • Event-free survival [ Time Frame: approximately 2.5 years ]
  • Overall Survival [ Time Frame: approximately 2.5 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lymphoma, Non Hodgkin
Intervention  ICMJE
  • Drug: Cyclophosphamide
    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.
  • Drug: Doxorubicin
    Doxorubicin will be administered at 50 mg/m^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.
  • Drug: Obinutuzumab
    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.
    Other Name: Gazyva/Gazyvaro
  • Drug: Polatuzumab Vedotin
    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.
    Other Name: DCDS4501A
  • Drug: Prednisolone
    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.
  • Drug: Prednisone
    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.
  • Drug: Rituximab
    Rituximab will be administered at 375 mg/m^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.
    Other Name: MabThera/Rituxan
Study Arms  ICMJE
  • Experimental: Polatuzumab Vedotin (1.4mg) + G-CHP
    Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP.
    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Doxorubicin
    • Drug: Obinutuzumab
    • Drug: Polatuzumab Vedotin
    • Drug: Prednisolone
    • Drug: Prednisone
  • Experimental: Polatuzumab Vedotin (1.0mg) + R-CHP
    Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.
    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Doxorubicin
    • Drug: Polatuzumab Vedotin
    • Drug: Prednisolone
    • Drug: Prednisone
    • Drug: Rituximab
  • Experimental: Polatuzumab Vedotin (1.8mg) + G-CHP
    Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP.
    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Doxorubicin
    • Drug: Obinutuzumab
    • Drug: Polatuzumab Vedotin
    • Drug: Prednisolone
    • Drug: Prednisone
  • Experimental: Polatuzumab Vedotin (1.4mg) + R-CHP
    Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.
    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Doxorubicin
    • Drug: Polatuzumab Vedotin
    • Drug: Prednisolone
    • Drug: Prednisone
    • Drug: Rituximab
  • Experimental: Polatuzumab Vedotin (1.8mg) + R-CHP
    Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.
    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Doxorubicin
    • Drug: Polatuzumab Vedotin
    • Drug: Prednisolone
    • Drug: Prednisone
    • Drug: Rituximab
  • Experimental: Polatuzumab Vedotin (2.4mg) + R-CHP
    Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.
    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Doxorubicin
    • Drug: Polatuzumab Vedotin
    • Drug: Prednisolone
    • Drug: Prednisone
    • Drug: Rituximab
  • Experimental: Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP
    Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.
    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Doxorubicin
    • Drug: Polatuzumab Vedotin
    • Drug: Prednisolone
    • Drug: Prednisone
    • Drug: Rituximab
  • Experimental: Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP
    Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP.
    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Doxorubicin
    • Drug: Obinutuzumab
    • Drug: Polatuzumab Vedotin
    • Drug: Prednisolone
    • Drug: Prednisone
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 7, 2017)
85
Original Estimated Enrollment  ICMJE
 (submitted: November 19, 2013)
90
Actual Study Completion Date  ICMJE December 19, 2018
Actual Primary Completion Date December 19, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01992653
Other Study ID Numbers  ICMJE GO29044
2013-003541-42 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Genentech, Inc.
Study Sponsor  ICMJE Genentech, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Genentech, Inc.
PRS Account Genentech, Inc.
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP