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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)

NCT02729896

Description:

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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
Recruiting Status:

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: BO29561
  • SECONDARY ID: 2015-004845-25
  • NCT ID: NCT02729896

Conditions

  • Lymphoma

Interventions

DrugSynonymsArms
Atezolizumab [TECENTRIQ]Dose-Escalation Phase
ObinutuzumabDose-Escalation Phase
Polatuzumab VedotinDose-Escalation Phase
RituximabExpansion Phase

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Dose-Escalation PhaseExperimentalDuring 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.
  • Atezolizumab [TECENTRIQ]
  • Obinutuzumab
  • Polatuzumab Vedotin
Expansion PhaseExperimentalFor 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).
  • Obinutuzumab
  • Polatuzumab Vedotin
  • Rituximab
Safety Run-In PhaseExperimentalFor DLBCL, during the induction treatment Cycles 1-6 (21-day cycles): participants will receive rituximab on Day 1 and Pola on Day 1.
  • Atezolizumab [TECENTRIQ]
  • Polatuzumab Vedotin
  • Rituximab

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Time Frame:Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
Safety Issue:
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.

Secondary Outcome Measures

Measure:Percentage of Participants With CR at EOI, as Determined by Investigator on the Basis of CT Scans Alone
Time Frame:Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
Safety Issue:
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.
Measure:Percentage of Participants With Objective Response (CR + PR) at EOI, as Determined by the Investigator on the Basis of PET-CT Scans
Time Frame:Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
Safety Issue:
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
Measure:Percentage of Participants With Objective Response (CR + PR) at EOI, as Determined by the Investigator on the Basis of CT Scans Alone
Time Frame:Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
Safety Issue:
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.
Measure: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
Time Frame:Baseline up to 35 months
Safety Issue:
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.
Measure:Percentage of Participants With Adverse Events and Serious Adverse Events
Time Frame:Baseline up to 35 months
Safety Issue:
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.
Measure:Serum Obinutuzumab Concentration
Time Frame:Pre-dose (0 hr) up to 35 months
Safety Issue:
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)
Measure:Serum Rituximab Concentration
Time Frame:Pre-dose (0 hr) up to 35 months
Safety Issue:
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)
Measure:Serum Atezo Concentration
Time Frame:Pre-dose (0 hr) up to 35 months
Safety Issue:
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)
Measure:Serum Pola Concentration
Time Frame:Pre-dose (0 hr) up to 35 months
Safety Issue:
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)
Measure:Percentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab
Time Frame:Baseline up to 35 months
Safety Issue:
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)
Measure:Percentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab
Time Frame:Baseline to 35 months
Safety Issue:
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)
Measure:Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo
Time Frame:Baseline to 35 months
Safety Issue:
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)
Measure:Percentage of Participants With ATAs to Pola
Time Frame:Baseline to 35 months
Safety Issue:
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)

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Hoffmann-La Roche

Last Updated

December 23, 2020