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

NCT ID: NCT03276468

Last Updated: 2023-01-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

136 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-02-12

Study Completion Date

2022-08-24

Brief Summary

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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)

Detailed Description

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Conditions

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Follicular Lymphoma Diffuse Large B Cell Lymphoma Marginal Zone Lymphoma Mucosa Associated Lymphoid Tissue

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

This study is a multicentric open-label phase II trial in 3 cohorts of patients
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Experimental

Combination of venetoclax, atezolizumab and obinutuzumab

Group Type EXPERIMENTAL

Atezolizumab

Intervention Type DRUG

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

Obinutuzumab

Intervention Type DRUG

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

Venetoclax

Intervention Type DRUG

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

Interventions

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Atezolizumab

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

Intervention Type 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

Intervention Type 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

Intervention Type DRUG

Other Intervention Names

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Tecentriq Gazyvaro Venclyxto

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Lymphoma Academic Research Organisation

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Guillaume CARTRON, PhD

Role: PRINCIPAL_INVESTIGATOR

Lymphoma Study Association

Charles HERBAUX, MD

Role: PRINCIPAL_INVESTIGATOR

Lymphoma Study Association

Locations

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CHU d'Angers

Angers, , France

Site Status

CHU de Caen

Caen, , France

Site Status

CHU de Clermont Ferrand - Estaing

Clermont-Ferrand, , France

Site Status

Hopital Henri Mondor

Créteil, , France

Site Status

CHU de Dijon

Dijon, , France

Site Status

CH Annecy Gennevois

Épagny, , France

Site Status

CHD de Vendée

La Roche-sur-Yon, , France

Site Status

CHU de Grenoble

La Tronche, , France

Site Status

CHRU de Lille

Lille, , France

Site Status

Centre Léon Bérard

Lyon, , France

Site Status

Institut Paoli Calmettes

Marseille, , France

Site Status

CHU de Montpellier

Montpellier, , France

Site Status

CHU de Nancy - Brabois

Nancy, , France

Site Status

CHU de Nantes

Nantes, , France

Site Status

CHU de Nice

Nice, , France

Site Status

Hôpital Saint Louis

Paris, , France

Site Status

Hôpital Necker

Paris, , France

Site Status

CHU Lyon Sud

Pierre-Bénite, , France

Site Status

CHU de Poitiers

Poitiers, , France

Site Status

CHU de Rennes - Hôpital de Pontchaillou

Rennes, , France

Site Status

Centre Henri Becquerel

Rouen, , France

Site Status

Institut Curie - Hôpital René Huguenin

Saint-Cloud, , France

Site Status

CHRU de Strasbourg

Strasbourg, , France

Site Status

Institut Universitaire du Cancer de Toulouse - Oncopole

Toulouse, , France

Site Status

CHRU de Tours

Tours, , France

Site Status

Countries

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France

Other Identifiers

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GATA

Identifier Type: -

Identifier Source: org_study_id

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