LymphomaPhase 1/2NCT02729896
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)
A Phase 1/2 study testing Atezolizumab [TECENTRIQ], Obinutuzumab and Polatuzumab Vedotin in people with Lymphoma, run by Hoffmann-La Roche at 19 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma
- What is being tested?
- Atezolizumab [TECENTRIQ], Obinutuzumab and Polatuzumab Vedotin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 19 sitesin 3 countries
- Study dates
- 9 Nov 2016to 7 Oct 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
19 sites in 3 countries.
19 sites in 3 countries
Germany8 sites
Städtisches Klinikum Dessau Klinik für Innere Medizin Abt. Intensivmedizin
Dessau, 06847
Uniklinik Essen
Essen, 45122
Universitatsklinikum Frankfurt
Frankfurt, 60590
Universitätsklinikum Greifswald Klinik für Innere Medizin C und Poliklinik
Greifswald, 17475
Medizinische Hochschule; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie
Hanover, 30625
Universitätsklinikum Jena Klinik f.Chirurgie Abt. Allgemein- und Viszeralchirurgie
Jena, 07747
Klinikum rechts der Isar der Technischen Universität München
München, 81675
Universitätsklinikum Würzburg
Würzburg, 97080
Poland6 sites
Szpitale Wojewodzkie w Gdyni Sp. z o.o.
Gdynia, 81-519
Wojewódzki Szpital Specjalistyczny im.MikołajaKopernika;KlinikaHematologiiUniwersytetuMedycznego
Lodz, 9351
MTZ Clinical Research Sp. z o.o.
Warsaw, 02-106
Instytut Hematologii i Transfuzjologii; Klinika Zaburzeń Hemostazy i Chorób Wewnętrznych
Warsaw, 02-776
Centrum Onkologii Instytut im. M. Sklodowskiej-Curie, Klinika Nowotworow Ukladu Chlonnego
Warsaw, 02-781
Medical Uni of Wroclaw; Hematology
Wroclaw, 50-367
United States5 sites
Columbia Basin Hem-Onc; Department Hematology Oncology
Kennewick, Washington, 99336
UCLA
Los Angeles, California, 90095
University Miami
Miami, Florida, 33136
Robert Byrd Health Science; Dept of Medicine, Section of Hematology/Oncology
Morgantown, West Virginia, 26506
Stony Brook University Hospital
Stony Brook, New York, 11794
About this study
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
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.
- Conditions
- Lymphoma
- Being tested
- Atezolizumab [TECENTRIQ], Obinutuzumab, Polatuzumab Vedotin, Rituximab
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atezolizumab [TECENTRIQ]Drug
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.
ObinutuzumabDrug
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).
Polatuzumab VedotinDrug
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).
RituximabDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| Dose-Escalation Phase | Experimental | 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. Receives: Drug: Atezolizumab [TECENTRIQ]; Drug: Obinutuzumab; Drug: Polatuzumab Vedotin |
| Expansion Phase | Experimental | 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). Receives: Drug: Obinutuzumab; Drug: Polatuzumab Vedotin; Drug: Rituximab |
| Safety Run-In Phase | Experimental | For DLBCL, during the induction treatment Cycles 1-6 (21-day cycles): participants will receive rituximab on Day 1 and Pola on Day 1. Receives: Drug: Atezolizumab [TECENTRIQ]; Drug: Polatuzumab Vedotin; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
Secondary outcomes (13)
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.
Measured: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
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
Measured: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
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.
Measured: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
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.
Measured: Baseline up to 35 months
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.
Measured: Baseline up to 35 months
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)
Measured: Pre-dose (0 hr) up to 35 months
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)
Measured: Pre-dose (0 hr) up to 35 months
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)
Measured: Pre-dose (0 hr) up to 35 months
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)
Measured: Pre-dose (0 hr) up to 35 months
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)
Measured: Baseline up to 35 months
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)
Measured: Baseline to 35 months
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)
Measured: Baseline to 35 months
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)
Measured: Baseline to 35 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2016 (estimated)
- Study start9 Nov 2016
- Primary completion3 Sep 2018
- Study completion7 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02729896
- Sponsor's protocol ID
- BO29561
- Other IDs
- 2015-004845-25, 2015
- Status last verified
- Nov 2020
- First submitted
- 1 Apr 2016
- Last updated
- 23 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 35182224
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02729896
- Acronym / sponsor ID
- BO29561
- Conditions
- Lymphoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 9 Nov 2016 (actual)
- Primary completion
- 3 Sep 2018 (actual)
- Study completion
- 7 Oct 2019 (actual)
- First posted
- 6 Apr 2016 (estimated)
- Results
- Posted 5 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose-Escalation Phase | Experimental | Drug: Atezolizumab [TECENTRIQ], Drug: Obinutuzumab, Drug: Polatuzumab VedotinDuring 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. |
| Expansion Phase | Experimental | Drug: Obinutuzumab, Drug: Polatuzumab Vedotin, Drug: RituximabFor 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). |
| Safety Run-In Phase | Experimental | Drug: Atezolizumab [TECENTRIQ], Drug: Polatuzumab Vedotin, Drug: RituximabFor DLBCL, during the induction treatment Cycles 1-6 (21-day cycles): participants will receive rituximab on Day 1 and Pola on Day 1. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Atezolizumab [TECENTRIQ]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. | Drug | Dose-Escalation Phase, Safety Run-In Phase |
| ObinutuzumabObinutuzumab 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). | Drug | Dose-Escalation Phase, Expansion Phase |
| Polatuzumab VedotinPolatuzumab 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). | Drug | Dose-Escalation Phase, Expansion Phase, Safety Run-In Phase |
| RituximabRituximab 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). | Drug | Expansion Phase, Safety Run-In Phase |
Primary outcome
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)
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.
13 secondary outcomes
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)
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)
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)
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
Percentage of Participants With Adverse Events and Serious Adverse Events
Time frame: Baseline up to 35 months
Serum Obinutuzumab Concentration
Time frame: Pre-dose (0 hr) up to 35 months
Serum Rituximab Concentration
Time frame: Pre-dose (0 hr) up to 35 months
Serum Atezo Concentration
Time frame: Pre-dose (0 hr) up to 35 months
Serum Pola Concentration
Time frame: Pre-dose (0 hr) up to 35 months
Percentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab
Time frame: Baseline up to 35 months
Percentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab
Time frame: Baseline to 35 months
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezo
Time frame: Baseline to 35 months
Percentage of Participants With ATAs to Pola
Time frame: Baseline to 35 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35182224Topp 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
19 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Atezolizumab [TECENTRIQ], Obinutuzumab and Polatuzumab Vedotin in people with Lymphoma, run by Hoffmann-La Roche at 19 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in Germany, Poland, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02729896, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Dec 2020.