Back to resultsA Study Evaluating Safety and Efficacy of Obinutuzumab, Polatuzumab Vedotin (Pola), and Atezolizumab (Atezo) in Participants With Relapsed or Refractory Follicular Lymphoma (FL) and Rituximab, Atezo, and Pola in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Primary Purpose
Lymphoma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Atezolizumab [TECENTRIQ]
Obinutuzumab
Polatuzumab Vedotin
Rituximab
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma
Eligibility Criteria
Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
- For obinutuzumab + Atezo + Pola treatment group: relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-Cluster of Differentiation (CD)20 monoclonal antibody and for which no other more appropriate treatment option exists as determined by the investigator
- For rituximab + Atezo + Pola treatment group: relapsed or refractory DLBCL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody, in participants who are not eligible for second line combination (immuno-) chemotherapy and autologous stem-cell transplantation or who have failed second line combination (immuno-) chemotherapy or experienced disease progression following autologous stem-cell transplantation
- Histologically documented CD20-positive lymphoma and fluorodeoxyglucose (FDG)-avid lymphoma (that is PET-positive lymphoma) with at least one bi-dimensionally measurable lesion
- Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of FL or DLBCL
- For women who are not postmenopausal or surgically sterile: agreement to remain abstinent or to use contraceptive methods that result in a failure rate of less than (<) 1% per year during the treatment period for greater than or equal to (>=) 5 months after last dose of Atezo, >= 12 months after last dose of rituximab, >= 12 months after last dose of Pola, and >= 18 months after last dose of obinutuzumab
- For men: agreement to remain abstinent or to use contraceptive measures that result in a failure rate of <1% per year during the treatment period and for at least 3 months after last dose of obinutuzumab, rituximab, and Atezo and for 5 months after last dose of Pola, and agreement to refrain from donating sperm during this same period
Exclusion Criteria:
- Grade 3b follicular lymphoma
- History of transformation of indolent disease to DLBCL
- Known CD20-negative status at relapse or progression; CNS lymphoma or leptomeningeal infiltration
- Prior allogeneic stem cell transplantation (SCT), completion of autologous SCT within 100 days prior to Day 1 of Cycle 1 (D1C1)
- Prior anti-cancer therapy including: Fludarabine or alemtuzumab within 12 months prior to D1C1; radioimmunoconjugate within 12 weeks prior to D1C1; monoclonal antibody or antibody drug conjugate (ADC) within 5 half-lives or 4 weeks prior to D1C1 ; radiotherapy, chemotherapy, hormonal therapy, or targeted small-molecule therapy within 2 weeks prior to D1C1; anti-programmed death-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4), anti-CD137/41-BB agonist, or anti-CD40 agonist antibodies
- Treatment with systemic immunosuppressive medications, including but not limited to prednisone, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to D1C1
- History of solid organ transplantation and of severe allergic or anaphylactic reaction to humanized, chimeric, or murine monoclonal antibodies
- Active infection; positive for hepatitis B surface agent (HbsAg), total hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) antibody at screening; known history of HIV positive status, progressive multifocal leukoencephalopathy (PML), autoimmune disease
- Vaccination with a live virus vaccine or live attenuated vaccine within 28 days prior to D1C1
- Pre-existing Grade greater than (>) 1 neuropathy
- Major surgical procedure other than for diagnosis within 28 days prior to D1C1
- Inadequate hematologic function, renal function, and liver function
- Pregnant or lactating women
- Life expectancy < 3 months
Sites / Locations
- UCLA
- University Miami
- Stony Brook University Hospital
- Columbia Basin Hem-Onc; Department Hematology Oncology
- Robert Byrd Health Science; Dept of Medicine, Section of Hematology/Oncology
- Städtisches Klinikum Dessau Klinik für Innere Medizin Abt. Intensivmedizin
- Uniklinik Essen
- Universitatsklinikum Frankfurt
- Universitätsklinikum Greifswald Klinik für Innere Medizin C und Poliklinik
- Medizinische Hochschule; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie
- Universitätsklinikum Jena Klinik f.Chirurgie Abt. Allgemein- und Viszeralchirurgie
- Klinikum rechts der Isar der Technischen Universität München
- Universitätsklinikum Würzburg
- Szpitale Wojewodzkie w Gdyni Sp. z o.o.
- Wojewódzki Szpital Specjalistyczny im.MikołajaKopernika;KlinikaHematologiiUniwersytetuMedycznego
- Instytut Hematologii i Transfuzjologii; Klinika Zaburzeń Hemostazy i Chorób Wewnętrznych
- MTZ Clinical Research Sp. z o.o.
- Centrum Onkologii Instytut im. M. Sklodowskiej-Curie, Klinika Nowotworow Ukladu Chlonnego
- Medical Uni of Wroclaw; Hematology
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Dose-Escalation Phase
Expansion Phase
Safety Run-In Phase
Arm Description
During the induction treatment Cycle 1 (21-day cycles): participants will receive obinutuzumab on Days 1, 8, and 15 and Pola on Day 1; Cycles 2-6: participants will receive obinutuzumab on Day 1, Atezo on Day 1, and Pola on Day 1. This is followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants.
For FL during the induction treatment Cycle 1 (21-day cycles): participants will receive obinutuzumab on Days 1, 8, and 15 and Pola at identified RP2D (decided from dose-escalation phase) on Day 1; Cycles 2-6: participants will receive obinutuzumab on Day 1 and Pola at RP2D on Day 1. This is followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months (during maintenance treatment for FL participants).
For DLBCL, during the induction treatment Cycles 1-6 (21-day cycles): participants will receive rituximab on Day 1 and Pola on Day 1.
Outcomes
Primary Outcome Measures
Percentage of Participants With CR at EOI, as Determined by the Investigator on the Basis of Positron Emission Tomography and Computed Tomography (PET-CT) Scan
Tumor response assessment was performed by the investigator according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. 90% confidence interval (CI) for percentage of responders was calculated using Clopper-Pearson method. All PET evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
Secondary Outcome Measures
Percentage of Participants With CR at EOI, as Determined by Investigator on the Basis of CT Scans Alone
Tumor response assessment was performed by investigator according to modified Lugano classification using computed tomography (CT) scan. OR: a response of CR or PR. CR: Target nodes/nodal masses regressed to <= 1.5 cm in LDi; no extralymphatic sites of disease; organ enlargement regressed to normal; no new lesions; normal/IHC-negative bone marrow morphology. All CT evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
Percentage of Participants With Objective Response (CR + PR) at EOI, as Determined by the Investigator on the Basis of PET-CT Scans
Tumor response assessment was performed by investigator according to modified Lugano classification using PET/CT scan. OR: a response of CR or PR. CR: a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with or without a residual mass on PET 5-PS, for lymph nodes & extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. PR with a score 4 (uptake moderately greater than [>] liver) or 5 (uptake markedly >liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites; no new lesions; and reduced residual uptake in bone marrow compared with baseline. All PET evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population
Percentage of Participants With Objective Response (CR + PR) at EOI, as Determined by the Investigator on the Basis of CT Scans Alone
Tumor response assessment was performed by investigator according to modified Lugano classification using CT scan. OR: a response of CR or PR. CR: Target nodes/nodal masses regressed to <= 1.5 cm in LDi; no extralymphatic sites of disease; organ enlargement regressed to normal; no new lesions; normal/IHC-negative bone marrow morphology. PR with >= 50 percet decrease in SPD of up to six target measurable nodes and extranodal sites, a 5 mm x 5 mm default value when lesions were too small, 0 x0 mm value when lesions were no longer visible, actual measurements were used for nodes greater than 5 mm x 5 mm for lymph nodes & extralymphatic sites; absent/normal, regression for non-measured lesion; spleen enlargement regression by > 50 percent; no new lesions; reduced residual uptake in bone marrow compared to baseline. All CT evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
Percentage of Participants With Best Response of CR or PR During the Study, as Determined by the Investigator on the Basis of CT Scans Alone
Tumor response assessment was performed by investigator according to modified Lugano classification using CT scan. OR: a response of CR or PR. CR: Target nodes/nodal masses regressed to <= 1.5 cm in LDi; no extralymphatic sites of disease; organ enlargement regressed to normal; no new lesions; normal/IHC-negative bone marrow morphology. PR with >= 50 percet decrease in SPD of up to six target measurable nodes and extranodal sites, a 5 mm x 5 mm default value when lesions were too small, 0 x0 mm value when lesions were no longer visible, actual measurements were used for nodes greater than 5 mm x 5 mm for lymph nodes & extralymphatic sites; absent/normal, regression for non-measured lesion; spleen enlargement regression by > 50 percent; no new lesions; reduced residual uptake in bone marrow compared to baseline. All CT evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
Percentage of Participants With Adverse Events and Serious Adverse Events
An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with the treatment. An adverse event was therefore any unfavourable 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. Grading was completed according to the CTCAE, version 4.0 for severity and tumor flare reactions were graded according to NCI CTCAE v3.0.
Serum Obinutuzumab Concentration
pre-dose (0 hr), 30 min after EOI on Day 1 Cycle 1; pre-dose (within 5 hr), 30 min after EOI on Day 1 of Cycles 2, 4, 6; maintenance phase: pre-dose (within 5 hr) on Day 1 of Months 1, 7, 13, 19; anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 50 mg/hr and decreases every 30 min to maximum of 400 mg/hr)
Serum Rituximab Concentration
pre-dose (0 hr), 30 min after EOI on Day 1 Cycle 1; pre-dose (within 5 hr) on Day 1 of Cycles 2, 4; pre-dose (within 5 hr), 30 min after EOI on Day 1 of Cycle 6; anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 50 mg/hr and increases every 30 min to maximum of 400 mg/hr)
Serum Atezo Concentration
pre-dose (within 5 hr), 30 min after EOI on Day 1 of Cycles 2, 3, 4; pre-dose (within 5 hr) on Day 1 of Cycle 6; maintenance phase: pre-dose (within 5 hr) on Day 1 of Month 1; 30 min after EOI on Day 2 of Month 1; pre-dose (within 5 hr) on Day 1 of Month 4, 7, 13, 19; anytime during treatment discontinuation visit, 120 days after the last dose, and 1-2 years after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 60 min and decreases to 30 min)
Serum Pola Concentration
pre-dose (0 hr) on Day 1 Cycle 1; pre-dose (within 5 hr) on Day 1 of Cycles 2, 4; maintenance phase: pre-dose (within 5 hr) on Day 1 of Months 1; anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 90 min and decreases to 30 min)
Percentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab
Pre-dose (0 hr) on Day 1 of Cycle 1, 6, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 50 mg/hr and increased every 30 min to maximum of 400 mg/hr)
Percentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab
Pre-dose (0 hr) on Day 1 of Cycle 1, 2, 4, 6, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 50 mg/hr and increased every 30 min to maximum of 400 mg/hr)
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo
Pre-dose (0 hr) on Day 1 of Cycle 2, 3, 4, 6, Month 1, 4, 7, 13 and 19, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 60 min and decreases to 30 min)
Percentage of Participants With ATAs to Pola
Pre-dose (0 hr) on Day 1 of Cycle 1, 2, 4, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 90 min and decreases to 30 min)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02729896
Brief Title
A Study Evaluating Safety and Efficacy of Obinutuzumab, Polatuzumab Vedotin (Pola), and Atezolizumab (Atezo) in Participants With Relapsed or Refractory Follicular Lymphoma (FL) and Rituximab, Atezo, and Pola in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Official Title
A Phase Ib/II Study Evaluating the Safety and Efficacy of Obinutuzumab in Combination With Atezolizumab Plus Polatuzumab Vedotin in Patients With Relapsed or Refractory Follicular Lymphoma and Rituximab in Combination With Atezolizumab Plus Polatuzumab Vedotin in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
November 9, 2016 (Actual)
Primary Completion Date
September 3, 2018 (Actual)
Study Completion Date
October 7, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
Brief Summary
This study will evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of obinutuzumab + Atezo + Pola in participants with relapsed or refractory (RR) FL and rituximab + Atezo + Pola in participants with RR DLBCL. The study will include an initial dose-escalation phase designed to determine the recommended Phase 2 dose (RP2D) for Pola in this treatment combination, followed by an expansion phase in which Pola will be given at the RP2D. All participants will receive induction treatment with obinutuzumab + Atezo + Pola for 6 cycles. RR FL participants achieving a complete response (CR), partial response (PR), or stable disease (SD) at the end of induction (EOI) will receive maintenance treatment with obinutuzumab.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
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
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dose-Escalation Phase
Arm Type
Experimental
Arm Description
During the induction treatment Cycle 1 (21-day cycles): participants will receive obinutuzumab on Days 1, 8, and 15 and Pola on Day 1; Cycles 2-6: participants will receive obinutuzumab on Day 1, Atezo on Day 1, and Pola on Day 1. This is followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants.
Arm Title
Expansion Phase
Arm Type
Experimental
Arm Description
For FL during the induction treatment Cycle 1 (21-day cycles): participants will receive obinutuzumab on Days 1, 8, and 15 and Pola at identified RP2D (decided from dose-escalation phase) on Day 1; Cycles 2-6: participants will receive obinutuzumab on Day 1 and Pola at RP2D on Day 1. This is followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months (during maintenance treatment for FL participants).
Arm Title
Safety Run-In Phase
Arm Type
Experimental
Arm Description
For DLBCL, during the induction treatment Cycles 1-6 (21-day cycles): participants will receive rituximab on Day 1 and Pola on Day 1.
Intervention Type
Drug
Intervention Name(s)
Atezolizumab [TECENTRIQ]
Intervention Description
Atezolizumab will be administered by intravenous (IV) infusion at a flat dose of 1200 milligram (mg) every 3 weeks (Q3W) on Day 1 of Cycles 2-6, given in 21-day cycles during induction treatment.
NOTE: Atezolizumab treatment has been discontinued in all participants currently on study treatment.
Intervention Type
Drug
Intervention Name(s)
Obinutuzumab
Intervention Description
Obinutuzumab will be administered by IV infusion at a flat dose of 1000 mg on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-6, given in 21-day cycles during induction treatment, and on Day 1 of every other month during maintenance treatment (1 cycle=21 days; infusion rate starts at 50 mg/hour (hr) and increases every 30 min to a maximum of 400 mg/hr).
Intervention Type
Drug
Intervention Name(s)
Polatuzumab Vedotin
Intervention Description
Polatuzumab vedotin will be administered by IV infusion. For relapsed or refractory FL either 1.4 mg/kilogram (kg) or 1.8 mg/kg (dose-escalation phase) and at RP2D (dose-expansion phase) on Day 1 of Cycles 1-6 will be given in 21-day cycles during induction treatment. For relapsed or refactory DLBCL, 1.8 mg/kg will be given during run-in phase and either 1.8 mg/kg or 1.4 mg/kg during the expansion phase (1 cycle=21 days; infusion rate starts with 90 min and decreases to 30 min).
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
Rituximab will be administered by IV infusion at 375 mg/m˄2 on Day 1 of Cycles 1-6 during induction treatment (1 cycle-21 days; infusion rate starts with 50 mg/hr and increases every 30 min to a maximum of 400 mg/hr).
Primary Outcome Measure Information:
Title
Percentage of Participants With CR at EOI, as Determined by the Investigator on the Basis of Positron Emission Tomography and Computed Tomography (PET-CT) Scan
Description
Tumor response assessment was performed by the investigator according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. 90% confidence interval (CI) for percentage of responders was calculated using Clopper-Pearson method. All PET evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
Time Frame
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
Secondary Outcome Measure Information:
Title
Percentage of Participants With CR at EOI, as Determined by Investigator on the Basis of CT Scans Alone
Description
Tumor response assessment was performed by investigator according to modified Lugano classification using computed tomography (CT) scan. OR: a response of CR or PR. CR: Target nodes/nodal masses regressed to <= 1.5 cm in LDi; no extralymphatic sites of disease; organ enlargement regressed to normal; no new lesions; normal/IHC-negative bone marrow morphology. All CT evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
Time Frame
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
Title
Percentage of Participants With Objective Response (CR + PR) at EOI, as Determined by the Investigator on the Basis of PET-CT Scans
Description
Tumor response assessment was performed by investigator according to modified Lugano classification using PET/CT scan. OR: a response of CR or PR. CR: a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with or without a residual mass on PET 5-PS, for lymph nodes & extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. PR with a score 4 (uptake moderately greater than [>] liver) or 5 (uptake markedly >liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites; no new lesions; and reduced residual uptake in bone marrow compared with baseline. All PET evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population
Time Frame
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
Title
Percentage of Participants With Objective Response (CR + PR) at EOI, as Determined by the Investigator on the Basis of CT Scans Alone
Description
Tumor response assessment was performed by investigator according to modified Lugano classification using CT scan. OR: a response of CR or PR. CR: Target nodes/nodal masses regressed to <= 1.5 cm in LDi; no extralymphatic sites of disease; organ enlargement regressed to normal; no new lesions; normal/IHC-negative bone marrow morphology. PR with >= 50 percet decrease in SPD of up to six target measurable nodes and extranodal sites, a 5 mm x 5 mm default value when lesions were too small, 0 x0 mm value when lesions were no longer visible, actual measurements were used for nodes greater than 5 mm x 5 mm for lymph nodes & extralymphatic sites; absent/normal, regression for non-measured lesion; spleen enlargement regression by > 50 percent; no new lesions; reduced residual uptake in bone marrow compared to baseline. All CT evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
Time Frame
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
Title
Percentage of Participants With Best Response of CR or PR During the Study, as Determined by the Investigator on the Basis of CT Scans Alone
Description
Tumor response assessment was performed by investigator according to modified Lugano classification using CT scan. OR: a response of CR or PR. CR: Target nodes/nodal masses regressed to <= 1.5 cm in LDi; no extralymphatic sites of disease; organ enlargement regressed to normal; no new lesions; normal/IHC-negative bone marrow morphology. PR with >= 50 percet decrease in SPD of up to six target measurable nodes and extranodal sites, a 5 mm x 5 mm default value when lesions were too small, 0 x0 mm value when lesions were no longer visible, actual measurements were used for nodes greater than 5 mm x 5 mm for lymph nodes & extralymphatic sites; absent/normal, regression for non-measured lesion; spleen enlargement regression by > 50 percent; no new lesions; reduced residual uptake in bone marrow compared to baseline. All CT evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
Time Frame
Baseline up to 35 months
Title
Percentage of Participants With Adverse Events and Serious Adverse Events
Description
An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with the treatment. An adverse event was therefore any unfavourable 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. Grading was completed according to the CTCAE, version 4.0 for severity and tumor flare reactions were graded according to NCI CTCAE v3.0.
Time Frame
Baseline up to 35 months
Title
Serum Obinutuzumab Concentration
Description
pre-dose (0 hr), 30 min after EOI on Day 1 Cycle 1; pre-dose (within 5 hr), 30 min after EOI on Day 1 of Cycles 2, 4, 6; maintenance phase: pre-dose (within 5 hr) on Day 1 of Months 1, 7, 13, 19; anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 50 mg/hr and decreases every 30 min to maximum of 400 mg/hr)
Time Frame
Pre-dose (0 hr) up to 35 months
Title
Serum Rituximab Concentration
Description
pre-dose (0 hr), 30 min after EOI on Day 1 Cycle 1; pre-dose (within 5 hr) on Day 1 of Cycles 2, 4; pre-dose (within 5 hr), 30 min after EOI on Day 1 of Cycle 6; anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 50 mg/hr and increases every 30 min to maximum of 400 mg/hr)
Time Frame
Pre-dose (0 hr) up to 35 months
Title
Serum Atezo Concentration
Description
pre-dose (within 5 hr), 30 min after EOI on Day 1 of Cycles 2, 3, 4; pre-dose (within 5 hr) on Day 1 of Cycle 6; maintenance phase: pre-dose (within 5 hr) on Day 1 of Month 1; 30 min after EOI on Day 2 of Month 1; pre-dose (within 5 hr) on Day 1 of Month 4, 7, 13, 19; anytime during treatment discontinuation visit, 120 days after the last dose, and 1-2 years after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 60 min and decreases to 30 min)
Time Frame
Pre-dose (0 hr) up to 35 months
Title
Serum Pola Concentration
Description
pre-dose (0 hr) on Day 1 Cycle 1; pre-dose (within 5 hr) on Day 1 of Cycles 2, 4; maintenance phase: pre-dose (within 5 hr) on Day 1 of Months 1; anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 90 min and decreases to 30 min)
Time Frame
Pre-dose (0 hr) up to 35 months
Title
Percentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab
Description
Pre-dose (0 hr) on Day 1 of Cycle 1, 6, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 50 mg/hr and increased every 30 min to maximum of 400 mg/hr)
Time Frame
Baseline up to 35 months
Title
Percentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab
Description
Pre-dose (0 hr) on Day 1 of Cycle 1, 2, 4, 6, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 50 mg/hr and increased every 30 min to maximum of 400 mg/hr)
Time Frame
Baseline to 35 months
Title
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo
Description
Pre-dose (0 hr) on Day 1 of Cycle 2, 3, 4, 6, Month 1, 4, 7, 13 and 19, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 60 min and decreases to 30 min)
Time Frame
Baseline to 35 months
Title
Percentage of Participants With ATAs to Pola
Description
Pre-dose (0 hr) on Day 1 of Cycle 1, 2, 4, anytime during treatment discontinuation visit, 120 days after the last dose, and 1 year after the last dose up to 35 months (1 cycle=21 days; infusion rate: starts with 90 min and decreases to 30 min)
Time Frame
Baseline to 35 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
For obinutuzumab + Atezo + Pola treatment group: relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-Cluster of Differentiation (CD)20 monoclonal antibody and for which no other more appropriate treatment option exists as determined by the investigator
For rituximab + Atezo + Pola treatment group: relapsed or refractory DLBCL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody, in participants who are not eligible for second line combination (immuno-) chemotherapy and autologous stem-cell transplantation or who have failed second line combination (immuno-) chemotherapy or experienced disease progression following autologous stem-cell transplantation
Histologically documented CD20-positive lymphoma and fluorodeoxyglucose (FDG)-avid lymphoma (that is PET-positive lymphoma) with at least one bi-dimensionally measurable lesion
Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of FL or DLBCL
For women who are not postmenopausal or surgically sterile: agreement to remain abstinent or to use contraceptive methods that result in a failure rate of less than (<) 1% per year during the treatment period for greater than or equal to (>=) 5 months after last dose of Atezo, >= 12 months after last dose of rituximab, >= 12 months after last dose of Pola, and >= 18 months after last dose of obinutuzumab
For men: agreement to remain abstinent or to use contraceptive measures that result in a failure rate of <1% per year during the treatment period and for at least 3 months after last dose of obinutuzumab, rituximab, and Atezo and for 5 months after last dose of Pola, and agreement to refrain from donating sperm during this same period
Exclusion Criteria:
Grade 3b follicular lymphoma
History of transformation of indolent disease to DLBCL
Known CD20-negative status at relapse or progression; CNS lymphoma or leptomeningeal infiltration
Prior allogeneic stem cell transplantation (SCT), completion of autologous SCT within 100 days prior to Day 1 of Cycle 1 (D1C1)
Prior anti-cancer therapy including: Fludarabine or alemtuzumab within 12 months prior to D1C1; radioimmunoconjugate within 12 weeks prior to D1C1; monoclonal antibody or antibody drug conjugate (ADC) within 5 half-lives or 4 weeks prior to D1C1 ; radiotherapy, chemotherapy, hormonal therapy, or targeted small-molecule therapy within 2 weeks prior to D1C1; anti-programmed death-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4), anti-CD137/41-BB agonist, or anti-CD40 agonist antibodies
Treatment with systemic immunosuppressive medications, including but not limited to prednisone, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to D1C1
History of solid organ transplantation and of severe allergic or anaphylactic reaction to humanized, chimeric, or murine monoclonal antibodies
Active infection; positive for hepatitis B surface agent (HbsAg), total hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) antibody at screening; known history of HIV positive status, progressive multifocal leukoencephalopathy (PML), autoimmune disease
Vaccination with a live virus vaccine or live attenuated vaccine within 28 days prior to D1C1
Pre-existing Grade greater than (>) 1 neuropathy
Major surgical procedure other than for diagnosis within 28 days prior to D1C1
Inadequate hematologic function, renal function, and liver function
Pregnant or lactating women
Life expectancy < 3 months
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Stony Brook University Hospital
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794
Country
United States
Facility Name
Columbia Basin Hem-Onc; Department Hematology Oncology
City
Kennewick
State/Province
Washington
ZIP/Postal Code
99336
Country
United States
Facility Name
Robert Byrd Health Science; Dept of Medicine, Section of Hematology/Oncology
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States
Facility Name
Städtisches Klinikum Dessau Klinik für Innere Medizin Abt. Intensivmedizin
City
Dessau-Roßlau
ZIP/Postal Code
06847
Country
Germany
Facility Name
Uniklinik Essen
City
Essen
ZIP/Postal Code
45122
Country
Germany
Facility Name
Universitatsklinikum Frankfurt
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
Universitätsklinikum Greifswald Klinik für Innere Medizin C und Poliklinik
City
Greifswald
ZIP/Postal Code
17475
Country
Germany
Facility Name
Medizinische Hochschule; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Universitätsklinikum Jena Klinik f.Chirurgie Abt. Allgemein- und Viszeralchirurgie
City
Jena
ZIP/Postal Code
07747
Country
Germany
Facility Name
Klinikum rechts der Isar der Technischen Universität München
City
Munchen
ZIP/Postal Code
81675
Country
Germany
Facility Name
Universitätsklinikum Würzburg
City
Wuerzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
Szpitale Wojewodzkie w Gdyni Sp. z o.o.
City
Gdynia
ZIP/Postal Code
81-519
Country
Poland
Facility Name
Wojewódzki Szpital Specjalistyczny im.MikołajaKopernika;KlinikaHematologiiUniwersytetuMedycznego
City
Lodz
ZIP/Postal Code
9351
Country
Poland
Facility Name
Instytut Hematologii i Transfuzjologii; Klinika Zaburzeń Hemostazy i Chorób Wewnętrznych
City
Warsaw
ZIP/Postal Code
02-776
Country
Poland
Facility Name
MTZ Clinical Research Sp. z o.o.
City
Warszawa
ZIP/Postal Code
02-106
Country
Poland
Facility Name
Centrum Onkologii Instytut im. M. Sklodowskiej-Curie, Klinika Nowotworow Ukladu Chlonnego
City
Warszawa
ZIP/Postal Code
02-781
Country
Poland
Facility Name
Medical Uni of Wroclaw; Hematology
City
Wroclaw
ZIP/Postal Code
50-367
Country
Poland
12. IPD Sharing Statement
Citations:
PubMed Identifier
35182224
Citation
Topp MS, Eradat H, Florschutz A, Hochhaus A, Wrobel T, Walewski J, Knopinska-Posluszny W, Kanate AS, Lech-Maranda E, Brunnberg U, Chitra S, Nielsen TG, Sellam G, Shivhare M, Lossos IS. Anti-CD20-atezolizumab-polatuzumab vedotin in relapsed/refractory follicular and diffuse large B-cell lymphoma. J Cancer Res Clin Oncol. 2023 Feb;149(2):811-817. doi: 10.1007/s00432-021-03847-5. Epub 2022 Feb 18.
Results Reference
derived
Learn more about this trial
A Study Evaluating Safety and Efficacy of Obinutuzumab, Polatuzumab Vedotin (Pola), and Atezolizumab (Atezo) in Participants With Relapsed or Refractory Follicular Lymphoma (FL) and Rituximab, Atezo, and Pola in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
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