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

January 9, 2023 updated by: The Lymphoma Academic Research Organisation

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)

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
136

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Angers, France, 49933
        • CHU d'Angers
      • Caen, France, 14000
        • CHU de Caen
      • Clermont-Ferrand, France, 63000
        • CHU de Clermont Ferrand - Estaing
      • Créteil, France, 94010
        • Hôpital Henri Mondor
      • Dijon, France, 21000
        • Chu de Dijon
      • Epagny, France, 74370
        • CH Annecy Gennevois
      • La Roche-sur-Yon, France, 85925
        • CHD de Vendée
      • La Tronche, France, 38700
        • CHU de Grenoble
      • Lille, France, 59037
        • CHRU de Lille
      • Lyon, France, 69373
        • Centre Leon Berard
      • Marseille, France, 13273
        • Institut Paoli Calmettes
      • Montpellier, France, 34295
        • CHU de Montpellier
      • Nancy, France, 54511
        • CHU de Nancy - Brabois
      • Nantes, France, 44093
        • CHU de Nantes
      • Nice, France, 62000
        • CHU de Nice
      • Paris, France, 75010
        • Hopital Saint Louis
      • Paris, France, 75015
        • Hopital Necker
      • Pierre Bénite, France, 69495
        • CHU Lyon Sud
      • Poitiers, France, 86021
        • Chu de Poitiers
      • Rennes, France, 35003
        • CHU de Rennes - Hôpital de Pontchaillou
      • Rouen, France, 76038
        • Centre Henri Becquerel
      • Saint-Cloud, France, 92210
        • Institut Curie - Hôpital René Huguenin
      • Strasbourg, France, 67100
        • CHRU de Strasbourg
      • Toulouse, France, 31100
        • Institut Universitaire du Cancer de Toulouse - Oncopole
      • Tours, France, 37044
        • Chru De Tours

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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)
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Experimental
Combination of venetoclax, atezolizumab and obinutuzumab
Drug: Atezolizumab
1200 mg on day 2 of each 21-day cycle during 18 months (24 cycles)
Other Names:
  • Tecentriq
Drug: Obinutuzumab
1000 mg on day 1, day 8 and day 15 of cycle 1 and each day 1 from cycle 2 to cycle 8
Other Names:
  • Gazyvaro
Drug: Venetoclax
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
Other Names:
  • Venclyxto

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
FL and DLBCL cohorts : Overall Metabolic Response Rate (OMRR) at the end of induction
Time Frame: 8 months (8 cycles)
Assessment of disease response according to Lugano 2014
8 months (8 cycles)
for iNHL cohort : Overall Response Rate (ORR) at the end of induction
Time Frame: 8 months (8 cycles)
Assessment of disease response according to Lugano 2014
8 months (8 cycles)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: 4 years
time from inclusion to the first observation of progression
4 years
Overall Survival (OS)
Time Frame: 4 years
time from inclusion to death
4 years
Duration of Response (DR)
Time Frame: 4 years
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
4 years
for FL and DLBCL cohorts : OMRR
Time Frame: 4 months, 18 months
According to Lugano 2014
4 months, 18 months
for iNHL cohort : ORR
Time Frame: 4 months, 18 months
According to Lugano 2014
4 months, 18 months
Best response
Time Frame: 18 months
Percentage of each response type according to Lugano 2014
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The Lymphoma Academic Research Organisation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Guillaume CARTRON, PhD, Lymphoma Study Association
  • Principal Investigator: Charles HERBAUX, MD, Lymphoma Study Association

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 12, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 19, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 24, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 7, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 7, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 8, 2017

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 10, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 9, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GATA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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