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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

Tracking Information
First Submitted Date  ICMJE September 7, 2017
First Posted Date  ICMJE September 8, 2017
Last Update Posted Date October 10, 2018
Actual Study Start Date  ICMJE February 12, 2018
Estimated Primary Completion Date November 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 7, 2017)
  • 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
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: September 7, 2017)
  • 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 for FL and DLBCL Assessment of disease response according to Lugano 2014
  • 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
Change History Complete list of historical versions of study NCT03276468 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 7, 2017)
  • Progression Free Survival (PFS) [ Time Frame: 4 years ]
    time from inclusion to the first observation of progression
  • Overall Survival (OS) [ Time Frame: 4 years ]
    time from inclusion to death
  • 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
  • for FL and DLBCL cohorts : OMRR [ Time Frame: 4 months, 18 months ]
    According to Lugano 2014
  • for iNHL cohort : ORR [ Time Frame: 4 months, 18 months ]
    According to Lugano 2014
  • Best response [ Time Frame: 18 months ]
    Percentage of each response type according to Lugano 2014
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of Atezolizumab-Venetoclax-Obinutuzumab Combination in Relapse/Refractory Lymphomas
Official Title  ICMJE A Phase II Trial Evaluating Combination of Atezolizumab, With Venetoclax and Obinutuzumab for Relapsed/Refractory Lymphomas
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)
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE
  • Follicular Lymphoma
  • Diffuse Large B Cell Lymphoma
  • Marginal Zone Lymphoma
  • Mucosa Associated Lymphoid Tissue
Intervention  ICMJE
  • 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
Study Arms  ICMJE Experimental: Experimental
Combination of venetoclax, atezolizumab and obinutuzumab
Interventions:
  • Drug: Atezolizumab
  • Drug: Obinutuzumab
  • Drug: Venetoclax
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 7, 2017)
138
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2021
Estimated Primary Completion Date November 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Julie ASSEMAT +334 72 66 93 33 julie.assemat@lysarc.org
Contact: Elise GAIRE +334 72 66 93 33 elise.gaire@lysarc.org
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03276468
Other Study ID Numbers  ICMJE GATA
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party The Lymphoma Academic Research Organisation
Study Sponsor  ICMJE The Lymphoma Academic Research Organisation
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Guillaume CARTRON, PhD Lymphoma Study Association
Principal Investigator: Charles HERBAUX, MD Lymphoma Study Association
PRS Account The Lymphoma Academic Research Organisation
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP