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LymphomaPhase 1NCT02220842

A Safety and Pharmacology Study of Atezolizumab (MPDL3280A) Administered With Obinutuzumab or Tazemetostat in Participants With Relapsed/Refractory Follicular Lymphoma and Diffuse Large B-cell Lymphoma

A Phase 1 study testing Atezolizumab, Obinutuzumab and Tazemetostat in people with Lymphoma, run by Hoffmann-La Roche at 15 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This open-label, multicenter, global study is designed to assess the safety, tolerability, preliminary efficacy, and pharmacokinetics of intravenous atezolizumab (MPDL3280A) and obinutuzumab in participants with refractory or relapsed follicular lymphoma (FL) or atezolizumab and obinutuzumab or tazemetostat… 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, Obinutuzumab and Tazemetostat
Could I receive a placebo?
No, everyone receives an active treatment
How many people
96 participants
Where
15 sitesin 5 countries
Study dates
18 Dec 2014to 21 Jan 2020
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Histologically documented, CD20-positive, relapsed or refractory (defined as having relapsed within 6 months to the previous treatment) FL or DLBCL (including primary mediastinal large B-cell lymphoma [PMLBCL])
  • Bone marrow biopsy at screening (unless it was performed within 3 months prior to screening)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
  • Life expectancy greater than or equal to (>=) 12 weeks
  • Has a QT interval corrected by Fridericia's formula (QTcF) less than or equal to (<=) 480 milliseconds (msec)
  • At least one bi-dimensionally measurable nodal lesion >1.5 cm in its longest diameter by computed tomography (CT) scan or MRI, as defined by the Lugano Classification
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  • Adequate hematologic and end-organ function
  • Archival tumor tissue
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 90 days after the last dose of atezolizumab or 18 months after the last dose of obinutuzumab, whichever is longer
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm

Who cannot join

  • Known central nervous system lymphoma, leptomeningeal lymphoma, or histologic evidence of transformation from an indolent lymphoma to a high-grade or DLBCL
  • Grade 3b FL, small lymphocytic lymphoma (SLL), or Waldenström's macroglobulinemia (WM) or other lymphoma subtypes except as stated in the inclusion criteria
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently); participants with indwelling catheters are eligible
  • Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
  • History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
  • Has had prior exposure to tazemetostat or other inhibitor(s) of enhancer of zeste homolog 2 (EZH2)
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  • Regular treatment with corticosteroids within the 2 or 4 weeks prior to the start of Cycle 1, unless administered for indications other than non-Hodgkin's lymphoma at a dose equivalent to < 30 mg/day prednisone/prednisolone
  • Pregnant and lactating women
  • History of autoimmune disease
  • Participants with history of confirmed progressive multifocal leukoencephalopathy (PML)
  • Participants with prior allogeneic bone marrow transplantation or prior solid organ transplantation
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis per chest CT scan at screening. History of radiation pneumonitis in the radiation field (fibrosis) is allowed
  • Positive test for Human Immunodeficiency Virus (HIV)
  • History of chronic hepatitis B infection or positive test results for active or chronic hepatitis B or hepatitis C
  • Significant cardiovascular disease, such as cardiac disease (New York Heart Association Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina
  • Hypersensitivity or prior treatment with obinutuzumab
  • Fludarabine or Campath within 12 months prior to study entry
  • Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
  • Treatment with systemic immunostimulatory agents (including but not limited to interferon, interleukin-2) within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1
  • Treatment with systemic immunosuppressive medications, including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor (anti-TNF) agents within 2 weeks prior to Cycle 1, Day 1; inhaled corticosteroids and mineralocorticoids are allowed
  • Participants with active tuberculosis (TB) will be excluded from the clinical trial

Trial locations and contacts

15 sites in 5 countries.

15 sites in 5 countries

United States7 sites

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599

  • City of Hope National Medical Center

    Duarte, California, 91010

  • Fort Wayne Neurological Center

    Fort Wayne, Indiana, 46805

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Sloan Kettering Cancer Center

    New York, New York, 10065-6007

  • UW- Fred Hutchinson Cancer Center

    Seattle, Washington, 98109

Other trials in United States

France5 sites

  • Hopital Claude Huriez - CHU Lille; Service des maladies du sang

    Lille, 59037

  • Hopital Saint Eloi

    Montpellier, 34295

  • Hôpital Saint-Louis

    Paris, 75475

  • Centre Hospitalier Lyon Sud

    Pierre-Bénite, 69495

  • Institut Gustave Roussy

    Villejuif, 94805

Other trials in France

Germany1 site

  • Universitaetsklinikum Freiburg

    Freiburg im Breisgau, 79106

Other trials in Germany

Italy1 site

  • Azienda Ospedaliera Città della Salute e della Scienza di Torino

    Turin, Piedmont, 10126

Other trials in Italy

United Kingdom1 site

  • Barts Hospital

    London, E1 2EF

Other trials in United Kingdom

About this study

Official title: A Phase Ib Study of the Safety and Pharmacology of Atezolizumab Administered With Obinutuzumab in Patients With Relapsed/Refractory Follicular Lymphoma or Atezolizumab Administered With Obinutuzumab or Tazemetostat in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

This open-label, multicenter, global study is designed to assess the safety, tolerability, preliminary efficacy, and pharmacokinetics of intravenous atezolizumab (MPDL3280A) and obinutuzumab in participants with refractory or relapsed follicular lymphoma (FL) or atezolizumab and obinutuzumab or tazemetostat administered in participants with refractory or relapsed diffuse large B-cell lymphoma (DLBCL). The anticipated duration of this study is approximately 4.5 years.

Conditions
Lymphoma
Being tested
Atezolizumab, Obinutuzumab, Tazemetostat
Medical subject headings
Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtezolizumabDrug

    Also called Tecentriq

    During safety evaluation stage, atezolizumab will be administered as 1200 milligrams (mg) intravenous (IV) infusion. During expansion stage, atezolizumab will be administered as either 1200 mg IV infusion or at dose decided from safety evaluation stage.

  • ObinutuzumabDrug

    During safety evaluation stage, obinutuzumab will be administered as 1000 mg IV infusion. During expansion stage, obinutuzumab will be administered as either 1000 mg IV infusion or at dose decided from safety evaluation stage.

  • TazemetostatDrug

    Also called EPZ6438

    Tazemetostat 800 mg will be administered orally, twice daily, on Days 1 to 21.

Study groups in NCT02220842
Study groupRoleWhat they receive
Arm 1 Cohort A (Safety Evaluation):Atezolizumab + ObinutuzumabExperimentalRelapsed/refractory FL and DLBCL participants will receive obinutuzumab alone on Days 1, 8, and 15 of Cycle 1 (Cycle length = 21 days), followed by atezolizumab and obinutuzumab on Day 1 of Cycles 2-8, and then atezolizumab alone on Day 1 of Cycle 9 and every cycle thereafter until unacceptable toxicities or disease progression.
Receives: Drug: Atezolizumab; Drug: Obinutuzumab
Arm 1 Cohort B (Expansion): Atezolizumab + ObinutuzumabExperimentalRelapsed/refractory FL participants will receive atezolizumab and obinutuzumab as per schedule and dose decided from the safety evaluation stage, until unacceptable toxicities or disease progression.
Receives: Drug: Atezolizumab; Drug: Obinutuzumab
Arm 1 Cohort C (Expansion): Atezolizumab + ObinutuzumabExperimentalRelapsed/refractory DLBCL participants will receive atezolizumab and obinutuzumab as per schedule and dose decided from the safety evaluation stage, until unacceptable toxicities or disease progression.
Receives: Drug: Atezolizumab; Drug: Tazemetostat
Arm 2 Cohort D (Safety Evaluation):Atezolizumab + TazemetostatExperimentalRelapsed/refractory DLBCL participants will receive atezolizumab (on Day 1) and tazemetostat (on Days 1-21) of each 21-day cycle until unacceptable toxicities or disease progression.
Receives: Drug: Atezolizumab; Drug: Tazemetostat
Arm 2 Cohort E (Expansion): Atezolizumab + TazemetostatExperimentalRelapsed/refractory DLBCL participants will receive atezolizumab and tazemetostat as per schedule and dose decided from the safety evaluation stage, until unacceptable toxicities or disease progression.
Receives: Drug: Atezolizumab; Drug: Tazemetostat

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Dose Limiting Toxicities (DLTs)

    Measured: 21 days (for Arm 1: Days 1 to 21 to Cycle 2; for Arm 2: Days 1 to 21 of Cycle 1, cycle length = 21 days)

  2. Recommended Phase 2 Dose (RP2D) of Atezolizumab

    Measured: 21 days (for Arm 1: Days 1 to 21 to Cycle 2; for Arm 2: Days 1 to 21 of Cycle 1, cycle length = 21 days)

Secondary outcomes (12)

  1. Obinutuzumab Minimum Serum Concentration (Cmin)

    Measured: Preinfusion (hour 0) on Day 1, 8, 15 of Cycle 1, Day 1 of Cycles 2, 3, 4, 6, 8, every 8 cycles thereafter up to treatment discontinuation, 120 days after treatment discontinuation (treatment discontinuation=up to approx 57 weeks) (Cycle=21 days)

  2. Percentage of Participants With Adverse Events (AEs) Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0)

    Measured: Baseline up to approximately 4.5 years

  3. Percentage of Participants With Anti-therapeutic Antibody Response to Atezolizumab and Obinutuzumab

    Measured: Baseline up to approximately 4.5 years

  4. Atezolizumab Maximum Serum Concentration (Cmax)

    Arm 1: preinfusion (hour 0) on Day 1 of Cycle 1, 30 minutes post end of atezolizumab infusion (infusion over 30-60 minutes) on Day 1 of Cycle 2, preinfusion on Day 1 of Cycles 3, 4, 6, 8, and every 8 cycles thereafter up to treatment discontinuation, 120 days after treatment discontinuation (treatment discontinuation=up to approx 57 weeks), additionally preinfusion on Day 1 of Cycle 9; Arm 2: preinfusion (hour 0) and 30 minutes post end of atezolizumab infusion (infusion over 30-60 minutes) on Day 1 of Cycles 1 and 3, preinfusion on Day 1 of Cycles 2, 8, every 8 cycles thereafter up to treatment discontinuation, 120 days after treatment discontinuation (treatment discontinuation=up to approx 57 weeks) (Cycle=21 days)

    Measured: Preinfusion (hour 0) on Day 1 of Cycle 1 up to approx 57 weeks (detailed timeframe is provided in outcome description section)

  5. Atezolizumab Minimum Serum Concentration (Cmin)

    Arm 1: preinfusion (hour 0) on Day 1 of Cycles 1, 3, 4, 6, 8, and every 8 cycles thereafter up to treatment discontinuation, 120 days after treatment discontinuation (treatment discontinuation=up to approx 57 weeks), pre-infusion on Day 1 of Cycle 9; Arm 2: preinfusion (hour 0) on Day 1 of Cycles 1, 2, 3, 8, every 8 cycles thereafter up to treatment discontinuation, 120 days after treatment discontinuation (treatment discontinuation=up to approx 57 weeks) (Cycle = 21 days)

    Measured: Preinfusion (hour 0) on Day 1 of Cycle 1 up to approx 57 weeks (detailed timeframe is provided in outcome description section)

  6. Obinutuzumab Maximum Serum Concentration (Cmax)

    Arm 1: preinfusion (hour 0) on Day 1, 4-hour post start of infusion on Day 2, preinfusion (hour 0) and 4-hour post start of infusion on Day 8, 15 of Cycle 1, Day 1 of Cycles 2, 3, 4, 6, 8, every 8 cycles thereafter up to treatment discontinuation, 120 days after treatment discontinuation (treatment discontinuation=up to approx 57 weeks) (Cycle=21 days)

    Measured: Arm 1: Preinfusion (hour 0) on Day 1 of Cycle 1 up to approx 57 weeks (detailed timeframe is provided in outcome description section)

  7. Percentage of Participants With Best Overall Response According to Lugano Classification

    Measured: Cycle 3 Day 15 (Cycle 4 Day 15 for Arm 1) up to progression of disease, death, or withdrawal of consent, whichever occurs first (up to approximately 4.5 years) (Cycle=21 days)

  8. Percentage of Participants With Objective Response (Complete Response or Partial Response) According to Lugano Classification

    Measured: Cycle 3 Day 15 (Cycle 4 Day 15 for Arm 1) up to progression of disease, death, or withdrawal of consent, whichever occurs first (up to approximately 4.5 years) (Cycle=21 days)

  9. Progression Free Survival (PFS) According to Lugano Classification

    Measured: Cycle 3 Day 15 (Cycle 4 Day 15 for Arm 1) up to progression of disease, death, or withdrawal of consent, whichever occurs first (up to approximately 4.5 years) (Cycle=21 days)

  10. Overall Survival (OS)

    Measured: Baseline until death due to any cause (up to approximately 4.5 years)

  11. Duration of Objective Response (DOR) According to Lugano Classification

    Measured: From first documented complete or partial response up to progression of disease, death, or withdrawal of consent, whichever occurs first (up to approximately 4.5 years)

  12. Tazemetostat Plasma Concentrations

    Measured: Arm 2: predose (hour 0) on Day 1 of Cycles 1, 2, 3, 4, 8, every 8 cycles thereafter up to Cycle 17; 1, 2, 4 hours post dose on Day 1 of Cycles 1 and 3; additionally (in Cohort E only) 0.5, 6, 8 hours post dose on Cycle 3 Day 1 (Cycle=21 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Aug 2014 (estimated)
  2. Study start18 Dec 2014
  3. Primary completion21 Jan 2020
  4. Study completion21 Jan 2020

Resources

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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
96 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02220842
Sponsor's protocol ID
GO29383
Other IDs
2014-001812-21, 2014
Status last verified
Jan 2020
First submitted
7 Aug 2014
Last updated
27 Jan 2020
Results posted
No

Publications

  • Palomba ML, Cartron G, Popplewell L, Ribrag V, Westin J, Huw LY, Agarwal S, Shivhare M, Hong WJ, Raval A, Chang AC, Penuel E, Morschhauser F. Combination of Atezolizumab and Tazemetostat in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Results From a Phase Ib Study. Clin Lymphoma Myeloma Leuk. 2022 Jul;22(7):504-512. doi: 10.1016/j.clml.2021.12.014. Epub 2021 Dec 24.

    PubMed 35151584

  • Palomba ML, Till BG, Park SI, Morschhauser F, Cartron G, Marks R, Shivhare M, Hong WJ, Raval A, Chang AC, Penuel E, Popplewell LL. Combination of Atezolizumab and Obinutuzumab in Patients with Relapsed/Refractory Follicular Lymphoma and Diffuse Large B-Cell Lymphoma: Results from a Phase 1b Study. Clin Lymphoma Myeloma Leuk. 2022 Jul;22(7):e443-e451. doi: 10.1016/j.clml.2021.12.010. Epub 2021 Dec 24.

    PubMed 35031227

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Atezolizumab, Obinutuzumab and Tazemetostat in people with Lymphoma, run by Hoffmann-La Roche at 15 sites in 5 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 10 inclusion and 21 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 27 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States, France, Germany, Italy, United Kingdom. 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 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.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 Dose Limiting Toxicities (DLTs) (time frame: 21 days (for Arm 1: Days 1 to 21 to Cycle 2; for Arm 2: Days 1 to 21 of Cycle 1, cycle length = 21 days)). The study lists 2 primary outcomes in all. 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 NCT02220842, which also lists 2 linked publications.

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 27 Jan 2020.

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