Clinical Trials /

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

NCT03276468

Description:

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)

Related Conditions:
  • B-Cell Lymphoma, Unclassifiable, with Features Intermediate between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue
  • Follicular Lymphoma
  • Grade 3b Follicular Lymphoma
  • Marginal Zone Lymphoma
  • Mediastinal Large B-Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Evaluation of Atezolizumab-Venetoclax-Obinutuzumab Combination in Relapse/Refractory Lymphomas
  • Official Title: A Phase II Trial Evaluating Combination of Atezolizumab, With Venetoclax and Obinutuzumab for Relapsed/Refractory Lymphomas

Clinical Trial IDs

  • ORG STUDY ID: GATA
  • NCT ID: NCT03276468

Conditions

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

Interventions

DrugSynonymsArms
AtezolizumabTecentriqExperimental
ObinutuzumabGazyvaroExperimental
VenetoclaxVenclyxtoExperimental

Purpose

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 Arms

NameTypeDescriptionInterventions
ExperimentalExperimentalCombination of venetoclax, atezolizumab and obinutuzumab
  • Atezolizumab
  • Obinutuzumab
  • Venetoclax

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:FL and DLBCL cohorts : Overall Metabolic Response Rate (OMRR) at the end of induction
Time Frame:8 months (8 cycles)
Safety Issue:
Description:Assessment of disease response according to Lugano 2014

Secondary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:4 years
Safety Issue:
Description:time from inclusion to the first observation of progression
Measure:Overall Survival (OS)
Time Frame:4 years
Safety Issue:
Description:time from inclusion to death
Measure:Duration of Response (DR)
Time Frame:4 years
Safety Issue:
Description: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
Measure:for FL and DLBCL cohorts : OMRR
Time Frame:4 months, 18 months
Safety Issue:
Description:According to Lugano 2014
Measure:for iNHL cohort : ORR
Time Frame:4 months, 18 months
Safety Issue:
Description:According to Lugano 2014
Measure:Best response
Time Frame:18 months
Safety Issue:
Description:Percentage of each response type according to Lugano 2014

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:The Lymphoma Academic Research Organisation

Trial Keywords

  • venetoclax; obinutuzumab; atezolizumab; lymphoma

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