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

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ClinicalTrials.gov Identifier: NCT03276468
Recruitment Status : Recruiting
First Posted : September 8, 2017
Last Update Posted : October 10, 2018
Sponsor:
Information provided by (Responsible Party):
The Lymphoma Academic Research Organisation

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)

Condition or disease Intervention/treatment Phase
Follicular Lymphoma Diffuse Large B Cell Lymphoma Marginal Zone Lymphoma Mucosa Associated Lymphoid Tissue Drug: Atezolizumab Drug: Obinutuzumab Drug: Venetoclax Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 138 participants
Intervention Model: Single Group Assignment
Intervention Model Description: This study is a multicentric open-label phase II trial in 3 cohorts of patients
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial Evaluating Combination of Atezolizumab, With Venetoclax and Obinutuzumab for Relapsed/Refractory Lymphomas
Actual Study Start Date : February 12, 2018
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : November 2021


Arm Intervention/treatment
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 Name: 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 Name: 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 Name: Venclyxto




Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: 4 years ]
    time from inclusion to the first observation of progression

  2. Overall Survival (OS) [ Time Frame: 4 years ]
    time from inclusion to death

  3. 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. for FL and DLBCL cohorts : OMRR [ Time Frame: 4 months, 18 months ]
    According to Lugano 2014

  5. for iNHL cohort : ORR [ Time Frame: 4 months, 18 months ]
    According to Lugano 2014

  6. Best response [ Time Frame: 18 months ]
    Percentage of each response type according to Lugano 2014



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03276468


Contacts
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Contact: Julie ASSEMAT +334 72 66 93 33 julie.assemat@lysarc.org
Contact: Elise GAIRE +334 72 66 93 33 elise.gaire@lysarc.org

Locations
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France
CHU d'Angers Active, not recruiting
Angers, France, 49933
CHU de Caen Active, not recruiting
Caen, France, 14000
CHU de Clermont Ferrand - Estaing Active, not recruiting
Clermont-Ferrand, France, 63000
Hopital Henri Mondor Active, not recruiting
Créteil, France, 94010
CHU de Dijon Recruiting
Dijon, France, 21000
Contact: Olivier CASASNOVAS, MD         
CH Annecy Gennevois Not yet recruiting
Epagny, France, 74370
Contact: Nicolas DAGUINDAU, MD         
CHD de Vendée Recruiting
La Roche-sur-Yon, France, 85925
Contact: Nadine Morineau, MD         
CHU de Grenoble Recruiting
La Tronche, France, 38700
Contact: Rémy Gressin, MD         
CHRU de Lille Recruiting
Lille, France, 59037
Contact: Franck Morschhauser, MD         
Centre Léon Bérard Active, not recruiting
Lyon, France, 69373
Institut Paoli Calmettes Active, not recruiting
Marseille, France, 13273
CHU de Montpellier Recruiting
Montpellier, France, 34295
Contact: Guillaume Cartron, PhD         
CHU de Nancy - Brabois Recruiting
Nancy, France, 54511
Contact: Pierre Feugier, MD         
CHU de Nantes Recruiting
Nantes, France, 44093
Contact: Steven Le Gouill, MD         
CHU de Nice Active, not recruiting
Nice, France, 62000
Hôpital Saint Louis Active, not recruiting
Paris, France, 75010
Hôpital Necker Active, not recruiting
Paris, France, 75015
CHU Lyon Sud Recruiting
Pierre Bénite, France, 69495
Contact: Gilles Salles, MD         
CHU de Poitiers Not yet recruiting
Poitiers, France, 86021
Contact: Vincent Delwail, MD         
CHU de Rennes - Hôpital de Pontchaillou Active, not recruiting
Rennes, France, 35003
Centre Henri Becquerel Recruiting
Rouen, France, 76038
Contact: Hervé Tilly, MD         
Institut Curie - Hôpital René Huguenin Active, not recruiting
Saint-Cloud, France, 92210
CHRU de Strasbourg Not yet recruiting
Strasbourg, France, 67100
Contact: Luc-Matthieu Fornecker, MD         
Institut Universitaire du Cancer de Toulouse - Oncopole Active, not recruiting
Toulouse, France, 31100
CHRU de Tours Active, not recruiting
Tours, France, 37044
Sponsors and Collaborators
The Lymphoma Academic Research Organisation
Investigators
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Principal Investigator: Guillaume CARTRON, PhD Lymphoma Study Association
Principal Investigator: Charles HERBAUX, MD Lymphoma Study Association

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Responsible Party: The Lymphoma Academic Research Organisation
ClinicalTrials.gov Identifier: NCT03276468     History of Changes
Other Study ID Numbers: GATA
First Posted: September 8, 2017    Key Record Dates
Last Update Posted: October 10, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by The Lymphoma Academic Research Organisation:
venetoclax; obinutuzumab; atezolizumab; lymphoma
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Atezolizumab
Venetoclax
Obinutuzumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological