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Follicular LymphomaPhase 2NCT03276468

Evaluation of Atezolizumab-Venetoclax-Obinutuzumab Combination in Relapse/Refractory Lymphomas

A Phase 2 study testing Atezolizumab, Obinutuzumab and Venetoclax in people with Follicular Lymphoma and Diffuse Large B Cell Lymphoma, run by The Lymphoma Academic Research Organisation at 25 sites in France.

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 study is a multicenter phase II trial which primary objective is to assess the anti-lymphoma activity of atezolizumab associated with a BCL-2 inhibitor (GDC-199, venetoclax) and an anti-CD20 monoclonal antibody (obinutuzumab) in three separate cohorts: relapsed/refractory follicular lymphoma (FL) patients… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Atezolizumab, Obinutuzumab and Venetoclax
Could I receive a placebo?
No, everyone receives an active treatment
How many people
136 participants
Where
25 sitesFrance
Study dates
12 Feb 2018to 24 Aug 2022
Phase
Phase 2
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 follicular lymphoma (WHO grade 1, 2, or 3a) patients for cohort 1
  • Patients with either histologically documented CD20-positive Diffuse large-cell lymphoma (including transformations of low-grade lymphoma into DLBCL) or follicular lymphoma CD20+ grade 3b, or primary cutaneous DLBCL leg type, or primary mediastinal (thymic) large B-cell lymphoma, or high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, or unclassifiable B-cell lymphoma with features intermediate between DLBCL and Hodgkin (WHO classification) for cohort 2
  • Patients with relapsed/refractory indolent lymphoma (marginal zone (MZL) or measurable mucosa-associated lymphoid tissue (MALT) lymphoma) for cohort 3
  • Relapsed/refractory NHL after ≥1 prior R-containing regimen with no curative option
  • Aged 18 years or more with no upper age limit
  • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
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  • Bi-dimensionally measurable disease defined by at least one single node or tumor lesion > 1.5 cm assessed by CT scan, or Positron Emission Tomography (PET) scan without IV contrast at diagnosis with at least one hypermetabolic lesion
  • Signed written informed consent
  • Life expectancy ≥ 3 months
  • Females of childbearing potential (FCBP) must agree to use one reliable form of contraception or to practice complete abstinence from heterosexual contact during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study; 3) dose interruptions; and 4) for at least 18 months after discontinuation of all study treatments
  • Male patients and their partner (FCBP) must agree to use two reliable forms of contraception (condom for males and hormonal method for partners) during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study; 3) dose interruptions; and 4) for at least 18 months after discontinuation of all study treatments
  • Patient covered by any social security system

Who cannot join

  • Lymphocytic lymphoma (LL), waldenström macroglobulinemia, unmeasurable MALT lymphoma, Mantle Cell Lymphoma (MCL) and Follicular lymphoma for cohort 3
  • Known CD20 negative status at last biopsy done (Biopsy at relapse/progression is mandatory)
  • Central nervous system or meningeal involvement by lymphoma
  • Prior history of Progressive Multifocal Leukoencephalopathy (PML)
  • Documented infection with HIV
  • Active Hepatitis B (HB) (positive Hepatitis B surface antigen (Ag-HBs) OR positive serology to hepatitis B (positive Ag-HBs or Hepatitis B core antibody (anti-HBc) or Polymerisation Chain Reaction (PCR) for viral DNA of HBV) Active Hepatitis C (HC) infection (patients with positive HCV serology (anti-HCV) are eligible only if PCR is negative from known HCV RNA)
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  • Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) before inclusion, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior to first administration of study drug
  • Active immune-related disease criteria
  • Left Ventricular Ejection Fraction (LVEF) < 45% as determined by echocardiography or multiple uptake gated acquisition (MUGA) scan
  • Any serious active disease or co-morbid medical condition (such as New York Heart Association Class III or IV cardiac disease, severe arrhythmia, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or pulmonary disease (including uncontrolled obstructive pulmonary disease and history of bronchospasm or other according to investigator's decision)
  • Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
  • Any of the following laboratory abnormalities:
  • Hemoglobin < 9 g/dL
  • Absolute neutrophil count (ANC) < 1,000 cells/mm3 (1.0 G/L) unless due to lymphoma
  • Platelet count < 75,000/mm3 (75 x 109/L) unless due to lymphoma
  • Serum glutamic-oxaloacetic transaminase (SGOT) / Aspartate Transaminase (AST) or Serum Glutamic-Pyruvate Transferase (SGPT) / Alanine Transaminase (ALT) 3.0 x upper limit of normal (ULN) unless disease involvement
  • Serum total bilirubin > 2.0 mg/dL (34 μmol/L), except if disease related or in case of Gilbert syndrome
  • Calculated creatinine clearance (Cockcroft-Gault formula or MDRD) of < 50 mL /min
  • International normalized ratio (INR) ≤ 1.5 x ULN for patients not receiving therapeutic anticoagulation
  • Partial thromboplastin time (PTT) or activated PTT (aPTT) > 1.5 x ULN
  • Prior history of malignancies other than lymphoma unless the subject has been free of the disease for ≥ 3 years. Exceptions will be allowed for patients with non-melanoma skin tumors (basal cell or squamous cell carcinoma of the skin) or any surgically removed stage 0 (in situ) carcinoma
  • Any serious medical condition, laboratory abnormality (other than mentioned above), or psychiatric illness that would prevent the subject from signing the informed consent form
  • Contraindication to any drug contained in the study treatment regimen
  • Previous treatment with obinutuzumab, atezolizumab or venetoclax
  • Use of any standard or experimental anti-cancer drug therapy within 28 days prior to first administration of study drug
  • Use of warfarin prior to first administration of study drug and throughout all treatment period (because of potential drug-drug interactions that may potentially increase the exposure of warfarin)
  • Patients taking corticosteroids within 4 weeks prior to first administration of study drug, unless administered at a cumulated dose equivalent to ≤ 3.5mg/kg (within these 4 weeks).
  • Use of the following agents prior to first administration of study drug: Strong and moderate CYP3A inhibitors (including grapefruit juice); Strong and moderate CYP3A inducers
  • Pregnant or lactating females
  • Person deprived of his/her liberty by a judicial or administrative decision
  • Adult person under legal protection
  • Person hospitalized without consent
  • Adult person unable to provide informed consent because of intellectual impairment, any serious medical condition, laboratory abnormality or psychiatric illness

Trial locations and contacts

25 sites in 1 country.

25 sites in 1 country

France25 sites

  • CHU d'Angers

    Angers, 49933

  • CHU de Caen

    Caen, 14000

  • CHU de Clermont Ferrand - Estaing

    Clermont-Ferrand, 63000

  • Hopital Henri Mondor

    Créteil, 94010

  • CHU de Dijon

    Dijon, 21000

  • CH Annecy Gennevois

    Épagny, 74370

  • CHD de Vendée

    La Roche-sur-Yon, 85925

  • CHU de Grenoble

    La Tronche, 38700

  • CHRU de Lille

    Lille, 59037

  • Centre Léon Bérard

    Lyon, 69373

  • Institut Paoli Calmettes

    Marseille, 13273

  • CHU de Montpellier

    Montpellier, 34295

  • CHU de Nancy - Brabois

    Nancy, 54511

  • CHU de Nantes

    Nantes, 44093

  • CHU de Nice

    Nice, 62000

  • Hôpital Saint Louis

    Paris, 75010

  • Hôpital Necker

    Paris, 75015

  • CHU Lyon Sud

    Pierre-Bénite, 69495

  • CHU de Poitiers

    Poitiers, 86021

  • CHU de Rennes - Hôpital de Pontchaillou

    Rennes, 35003

  • Centre Henri Becquerel

    Rouen, 76038

  • Institut Curie - Hôpital René Huguenin

    Saint-Cloud, 92210

  • CHRU de Strasbourg

    Strasbourg, 67100

  • Institut Universitaire du Cancer de Toulouse - Oncopole

    Toulouse, 31100

  • CHRU de Tours

    Tours, 37044

Other trials in France

About this study

Official title: A Phase II Trial Evaluating Combination of Atezolizumab, With Venetoclax and Obinutuzumab for Relapsed/Refractory Lymphomas

This study is a multicenter phase II trial which primary objective is to assess the anti-lymphoma activity of atezolizumab associated with a BCL-2 inhibitor (GDC-199, venetoclax) and an anti-CD20 monoclonal antibody (obinutuzumab) in three separate cohorts:

  • relapsed/refractory follicular lymphoma (FL) patients
  • relapsed/refractory aggressive (DLBCL) lymphoma patients
  • relapsed/refractory other indolent (iNHL) lymphoma patients (MZL and MALT)
Keywords
venetoclax; obinutuzumab; atezolizumab; lymphoma
Medical subject headings
Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse, Lymphoma, B-Cell, Marginal Zone, Lymphoma

What participants receive

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

  • AtezolizumabDrug

    Also called Tecentriq

    1200 mg on day 2 of each 21-day cycle during 18 months (24 cycles)

  • ObinutuzumabDrug

    Also called Gazyvaro

    1000 mg on day 1, day 8 and day 15 of cycle 1 and each day 1 from cycle 2 to cycle 8

  • VenetoclaxDrug

    Also called Venclyxto

    800 mg/d from day 8 of cycle 1, every day during 18 months. For MZL patients wiht lymphocytes>5 g/l : 50 mg/day: week 1 100mg/day: week 2 200mg/day: week 3 400mg/day: week 4 800mg/day: from week 5

Study groups in NCT03276468
Study groupRoleWhat they receive
ExperimentalExperimentalCombination of venetoclax, atezolizumab and obinutuzumab
Receives: Drug: Atezolizumab; Drug: Obinutuzumab; Drug: Venetoclax

What is being measured

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

  1. FL and DLBCL cohorts : Overall Metabolic Response Rate (OMRR) at the end of induction

    Assessment of disease response according to Lugano 2014

    Measured: 8 months (8 cycles)

  2. for iNHL cohort : Overall Response Rate (ORR) at the end of induction

    Assessment of disease response according to Lugano 2014

    Measured: 8 months (8 cycles)

Secondary outcomes (6)

  1. Progression Free Survival (PFS)

    time from inclusion to the first observation of progression

    Measured: 4 years

  2. Overall Survival (OS)

    time from inclusion to death

    Measured: 4 years

  3. Duration of Response (DR)

    from a confirmed Complete Metabolic Response / Complete Radiologic Response (CMR/CRR) or Partial Metabolic Response / Partial Radiologic Response (PMR/PRR) the first observation of progression

    Measured: 4 years

  4. for FL and DLBCL cohorts : OMRR

    According to Lugano 2014

    Measured: 4 months, 18 months

  5. for iNHL cohort : ORR

    According to Lugano 2014

    Measured: 4 months, 18 months

  6. Best response

    Percentage of each response type according to Lugano 2014

    Measured: 18 months

Timeline

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

  1. First posted8 Sep 2017
  2. Study start12 Feb 2018
  3. Primary completion19 Sep 2019
  4. Study completion24 Aug 2022

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
This study is a multicentric open-label phase II trial in 3 cohorts of patients
Masking
None (open label)
Enrolment
136 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03276468
Sponsor's protocol ID
GATA
Status last verified
Jan 2023
First submitted
7 Sep 2017
Last updated
10 Jan 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Atezolizumab, Obinutuzumab and Venetoclax in people with Follicular Lymphoma and Diffuse Large B Cell Lymphoma, run by The Lymphoma Academic Research Organisation at 25 sites in France.

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 12 inclusion and 33 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 10 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in France. 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 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?

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?

FL and DLBCL cohorts : Overall Metabolic Response Rate (OMRR) at the end of induction (time frame: 8 months (8 cycles)). 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 NCT03276468.

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 10 Jan 2023.

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