NCT03276468

Brief 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
  • relapsed/refractory aggressive (DLBCL) lymphoma patients
  • relapsed/refractory other indolent (iNHL) lymphoma patients (MZL and MALT)

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
136

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Feb 2018

Typical duration for phase_2

Geographic Reach
1 country

25 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 7, 2017

Completed
1 day until next milestone

First Posted

Study publicly available on registry

September 8, 2017

Completed
5 months until next milestone

Study Start

First participant enrolled

February 12, 2018

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 19, 2019

Completed
2.9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 24, 2022

Completed
Last Updated

January 10, 2023

Status Verified

January 1, 2023

Enrollment Period

1.6 years

First QC Date

September 7, 2017

Last Update Submit

January 9, 2023

Conditions

Follicular LymphomaDiffuse Large B Cell LymphomaMarginal Zone LymphomaMucosa Associated Lymphoid Tissue

Keywords

venetoclax; obinutuzumab; atezolizumab; lymphoma

Outcome Measures

Primary Outcomes (2)

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

    Assessment of disease response according to Lugano 2014

    8 months (8 cycles)

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

    Assessment of disease response according to Lugano 2014

    8 months (8 cycles)

Secondary Outcomes (6)

  • Progression Free Survival (PFS)

    4 years

  • Overall Survival (OS)

    4 years

  • Duration of Response (DR)

    4 years

  • for FL and DLBCL cohorts : OMRR

    4 months, 18 months

  • for iNHL cohort : ORR

    4 months, 18 months

  • +1 more secondary outcomes

Study Arms (1)

Experimental

EXPERIMENTAL

Combination of venetoclax, atezolizumab and obinutuzumab

Drug: AtezolizumabDrug: ObinutuzumabDrug: Venetoclax

Interventions

AtezolizumabDRUG

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

Also known as: Tecentriq
Experimental
ObinutuzumabDRUG

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

Also known as: Gazyvaro
Experimental
VenetoclaxDRUG

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

Also known as: Venclyxto
Experimental

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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)
  • 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
  • +17 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (25)

CHU d'Angers

Angers, 49933, France

Location

CHU de Caen

Caen, 14000, France

Location

CHU de Clermont Ferrand - Estaing

Clermont-Ferrand, 63000, France

Location

Hopital Henri Mondor

Créteil, 94010, France

Location

CHU de Dijon

Dijon, 21000, France

Location

CH Annecy Gennevois

Épagny, 74370, France

Location

CHD de Vendée

La Roche-sur-Yon, 85925, France

Location

CHU de Grenoble

La Tronche, 38700, France

Location

CHRU de Lille

Lille, 59037, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

CHU de Montpellier

Montpellier, 34295, France

Location

CHU de Nancy - Brabois

Nancy, 54511, France

Location

CHU de Nantes

Nantes, 44093, France

Location

CHU de Nice

Nice, 62000, France

Location

Hôpital Saint Louis

Paris, 75010, France

Location

Hôpital Necker

Paris, 75015, France

Location

CHU Lyon Sud

Pierre-Bénite, 69495, France

Location

CHU de Poitiers

Poitiers, 86021, France

Location

CHU de Rennes - Hôpital de Pontchaillou

Rennes, 35003, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Institut Curie - Hôpital René Huguenin

Saint-Cloud, 92210, France

Location

CHRU de Strasbourg

Strasbourg, 67100, France

Location

Institut Universitaire du Cancer de Toulouse - Oncopole

Toulouse, 31100, France

Location

CHRU de Tours

Tours, 37044, France

Location

MeSH Terms

Conditions

Lymphoma, FollicularLymphoma, Large B-Cell, DiffuseLymphoma, B-Cell, Marginal ZoneLymphoma

Interventions

atezolizumabobinutuzumabvenetoclax

Condition Hierarchy (Ancestors)

Lymphoma, Non-HodgkinNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLymphoma, B-Cell

Study Officials

  • Guillaume CARTRON, PhD

    Lymphoma Study Association

    PRINCIPAL INVESTIGATOR

  • Charles HERBAUX, MD

    Lymphoma Study Association

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: This study is a multicentric open-label phase II trial in 3 cohorts of patients
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 7, 2017

First Posted

September 8, 2017

Study Start

February 12, 2018

Primary Completion

September 19, 2019

Study Completion

August 24, 2022

Last Updated

January 10, 2023

Record last verified: 2023-01

Data Sharing

IPD Sharing
Will not share

Locations

FR(25)