Clinical trial NCT02005471: A Study to Evaluate the Benefit of Venetoclax Plus Rituximab Compared With Bendamustine Plus Rituximab in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
Official title: A Multicenter, Phase III, Open-Label, Randomized Study in Relapsed/Refractory Patients With Chronic Lymphocytic Leukemia to Evaluate the Benefit of Venetoclax (GDC-0199/ABT-199) Plus Rituximab Compared With Bendamustine Plus Rituximab
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Lymphocytic Leukemia
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: AbbVie
First posted: 2013-12-09
Enrollment: 389
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this open-label, multicenter, randomized, Phase III study is to evaluate the benefit of venetoclax in combination with rituximab compared with bendamustine in combination with rituximab in participants with relapsed or refractory CLL. Participants will be randomly assigned in 1:1 ratio to receive either venetoclax + rituximab (Arm A) or bendamustine + rituximab (Arm B).


Eligibility criteria: Inclusion Criteria:

* Diagnosis of CLL per diagnostic criteria for relapsed or refractory CLL per the international workshop on chronic lymphocytic leukemia (iwCLL) guidelines
* Previously treated with 1-3 lines of therapy (example: completed greater than or equal to \[\>/=\] 2 treatment cycles per therapy), including at least one standard chemotherapy-containing regimen
* Participants previously treated with bendamustine only if their duration of response was \>/= 24 months
* Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to (\</=) 1
* Adequate bone marrow function
* Adequate renal and hepatic function
* Participants must use effective birth control throughout study until at least 30 days after study treatment or 1 year after rituximab treatment, whichever is later; female participants must not be pregnant or breast-feeding
* For participants with the 17p deletion, previously treated with 1-3 lines of therapy, including at least one prior standard chemotherapy-containing regimen or at least one prior alemtuzumab-containing therapy

Inclusion Criteria R/C Substudy:

* Participants randomized to Arm A or Arm B with a confirmed disease progression of CLL per iwCLL criteria
* Participants who have not received new anti-CLL therapy following disease progression in Arm A or Arm B
* Adequate renal and hepatic function per laboratory reference range

Exclusion Criteria:

* Transformation of CLL to aggressive non-Hodgkin lymphoma or central nervous system (CNS) involvement by CLL
* Undergone an allogenic stem cell transplant
* A history of significant renal, neurologic, psychiatric, endocrine, metabolic, immunologic, cardiovascular or hepatic disease
* Hepatitis B or C or known human immunodeficiency virus (HIV) positive
* Receiving warfarin treatment
* Received an anti-CLL monoclonal antibody within 8 weeks prior to the first dose of study drug
* Received any anti-cancer or investigational therapy within 28 days prior to the first dose of study drug or has not recovered to less than Grade 2 clinically significant adverse effect(s)/toxicity(ies) of any previous therapy
* Received cytochrome P450 3A4 (CYP3A4) inhibitors (such as fluconazole, ketoconazole and clarithromycin) or inducers (such as rifampin, carbamazapine, phenytoin, St. John's Wort) within 7 days prior to the first dose of venetoclax
* History of prior venetoclax treatment
* Participants with another cancer, history of another cancer considered uncured on in complete remission for \<5 years, or currently under treatment for another suspected cancer except non-melanoma skin cancer or carcinoma in situ of the cervix that has been treated or excised and is considered resolved
* Malabsorption syndrome or other condition that precludes enteral route of administration
* Other clinically significant uncontrolled condition(s) including, but not limited to, systemic infection (viral, bacterial or fungal)
* Vaccination with a live vaccine within 28 days prior to randomization
* Consumed grapefruit or grapefruit products, seville oranges (including marmalade containing seville oranges), or star fruit within 3 days prior to the first dose of study treatment
* A cardiovascular disability status of New York Heart Association Class \>/=3. Class 3 is defined as cardiac disease in which participants are comfortable at rest but have marked limitation of physical activity due to fatigue, palpitations, dyspnea, or anginal pain
* Major surgery within 30 days prior to the first dose of study treatment
* A participant who is pregnant or breastfeeding
* Known allergy to both xanthine oxidase inhibitors and rasburicase

Exclusion Criteria R/C Substudy:

* Transformation of CLL to aggressive NHL (e.g., Richter's transformation, prolymphocytic leukemia, or DLBCL) or CNS involvement by CLL
* Evidence of other clinically significant uncontrolled condition(s) including, but not limited to, uncontrolled systemic infection (viral, bacterial, or fungal)
* Development of other malignancy since enrollment into the study, with the exception of curatively treated basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
* Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
* History of severe (i.e., requiring permanent discontinuation of prior rituximab therapy) prior allergic or anaphylactic reactions to rituximab
* Known HIV positivity
* Positive test results for chronic hepatitis B infection (defined as positive hepatitis B surface antigen \[HbsAg\] serology)
* Positive test results for hepatitis C virus (HCV; HCV antibody serology testing)
* Requires the use of warfarin (due to potential drug interactions that may potentially increase the exposure of warfarin)
* Has not recovered to less than Grade 2 clinically significant adverse effect(s)/toxicity(ies) of any previous therapy
* Received potent CYP3A4 inhibitors (such as fluconazole, ketoconazole, and clarithromycin) within 7 days prior to the first dose of study treatment
* Received potent CYP3A4 inducers (such as rifampin, carbamazepine, phenytoin, St. John's wort) within 7 days prior to the first dose of study treatment
* Consumed grapefruit or grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of study treatment
* A cardiovascular disability status of New York Heart Association Class \>/= 3
* A significant history of renal, neurologic, psychiatric, endocrine, metabolic, immunologic, cardiovascular, or hepatic disease that, in the opinion of the investigator, would adversely affect the participants's participation in this study or interpretation of study outcomes
* Major surgery within 30 days prior to the first dose of study treatment
* A participant who is pregnant or breastfeeding
* Malabsorption syndrome or other condition that precludes enteral route of administration
* Known allergy to both xanthine oxidase inhibitors and rasburicase
* Vaccination with a live vaccine within 28 days prior to randomization

Primary outcomes:
measure: Percentage of Participants With PD as Assessed by the Investigator Using Standard International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Guidelines or Death
timeFrame: Baseline up to PD or death from any cause, whichever occurred first (up to approximately 8 years 5 months)
measure: Progression-Free Survival (PFS) as Assessed by the Investigator Using Standard iwCLL Guidelines
timeFrame: Baseline up to PD or death, whichever occurred first (up to approximately 8 years 5 months)
Secondary outcomes:
measure: Percentage of Participants With PD or Death as Assessed by the Independent Review Committee (IRC) Using Standard iwCLL Guidelines
timeFrame: Baseline up to PD or death, whichever occurred first (up to approximately 3 years)
measure: PFS as Assessed by the IRC Using Standard iwCLL Guidelines
timeFrame: Baseline up to PD or death, whichever occurred first (up to approximately 3 years)
measure: Percentage of Participants With PD or Death as Assessed by the Investigator Using Standard iwCLL Guidelines in Participants With 17p Deletion as Identified by Fluorescence In-situ Hybridization (FISH) Test
timeFrame: Baseline up to PD or death, whichever occurred first (up to approximately 8 years 5 months)
measure: PFS as Assessed by the Investigator Using Standard iwCLL Guidelines in Participants With 17p Deletion as Identified by FISH Test
timeFrame: Baseline up to PD or death, whichever occurred first (up to approximately 8 years 5 months)
measure: Percentage of Participants With PD or Death as Assessed by the IRC Using Standard iwCLL Guidelines in Participants With 17p Deletion as Identified by FISH Test
timeFrame: Baseline up to PD or death, whichever occurred first (up to approximately 3 years)
measure: PFS as Assessed by the IRC Using Standard iwCLL Guidelines in Participants With 17p Deletion as Identified by FISH Test
timeFrame: Baseline up to PD or death, whichever occurred first (up to approximately 3 years)
measure: Percentage of Participants With Best Overall Response of Complete Response (CR), CR With Incomplete Bone Marrow Recovery (CRi), Nodular Partial Response (nPR), or Partial Response (PR) as Assessed by the Investigator Using iwCLL Guidelines
timeFrame: Baseline up to approximately 8 years 5 months
measure: Percentage of Participants With Best Overall Response of CR, CRi, nPR, or PR as Assessed by the IRC Using iwCLL Guidelines
timeFrame: Baseline up to last FUV (up to approximately 3 years)
measure: Percentage of Participants With Overall Response of CR, Cri, nPR, or PR at End of Combination Treatment Visit as Assessed by the Investigator Using iwCLL Guidelines
timeFrame: End of combination treatment response (EoCTR) visit (8 to 12 weeks after Cycle [C] 6 Day [1]); Cycle length = 28 days
measure: Percentage of Participants With Overall Response of CR, Cri, nPR, or PR at End of Combination Treatment Visit as Assessed by the IRC Using iwCLL Guidelines
timeFrame: EoCTR visit (8 to 12 weeks after C6D1); Cycle length = 28 days
measure: Percentage of Participants Who Died
timeFrame: Baseline up to approximately 8 years 5 months
measure: Overall Survival (OS)
timeFrame: Baseline up to approximately 8 years 5 months
measure: Percentage of Participants With PD/Relapse, Start of a New Anti-Chronic Lymphocytic Leukemia (CLL) Therapy, or Death as Assessed by the Investigator Using iwCLL Guidelines
timeFrame: Baseline up to PD/relapse, start of a new anti-CLL therapy, or death from any cause, whichever occurred first (approximately 8 years 5 months)
measure: Event-Free Survival (EFS) as Assessed by the Investigator Using iwCLL Guidelines
timeFrame: Baseline up to PD/relapse, start of a new anti-CLL therapy, or death from any cause, whichever occurred first (approximately 8 years 5 months)
measure: Percentage of Participants With PD or Death Among Participants With Best Overall Response of CR, CRi, nPR, or PR as Assessed by the Investigator Using iwCLL Guidelines
timeFrame: From time of achieving best overall response until PD or death from any cause, whichever occurred first (up to approximately 8 years 5 months)
measure: Duration of Responses (DOR) as Assessed by the Investigator Using iwCLL Guidelines
timeFrame: From time of achieving best overall response until PD or death from any cause, whichever occurred first (up to approximately 8 years 5 months)
measure: Percentage of Participants With Start of New Anti-CLL Treatment or Death as Assessed by the Investigator
timeFrame: Baseline up to start of new ani-CLL therapy or death, whichever occurred first (up to approximately 8 years 5 months)
measure: Time to New Anti-CLL Treatment (TTNT) as Assessed by the Investigator
timeFrame: Baseline up to start of new ani-CLL therapy or death, whichever occurred first (up to approximately 8 years 5 months)
measure: Percentage of Participants With Minimal Residual Disease (MRD) Negativity in Peripheral Blood
timeFrame: EoCTR visit (8 to 12 weeks after C6D1); Cycle length = 28 days
measure: Percentage of Participants With MRD Negativity in Bone Marrow
timeFrame: EoCTR visit (8 to 12 weeks after C6D1); Cycle length = 28 days
measure: Plasma Venetoclax Concentrations
timeFrame: Pre-dose (0 hour, anytime before venetoclax administration) and 4 hours post-dose on D1 of Cycles 1 and 4; Cycle length = 28 days
measure: Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Core Symptom Severity, Module Symptom Severity, and Interference Scores
timeFrame: Baseline, Days 1, 8, and 15 of Cycles 1, 2, and 3; Cycle length = 28 days
measure: Change From Baseline in HRQoL as Measured by European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) Functional Scales Score and Global Health Status/Global Quality-of-Life (QoL) Scale Score
timeFrame: Baseline, D1 of Cycles 1, 2, 3, 4, 5, 6, STC/EW visit (up to C6D28), EoCTR visit (8 to 12 weeks after C6D1), and FUVs (every 12 weeks after EoCTR up to 3 years); Cycle length = 28 days
measure: Change From Baseline in HRQoL as Measured by Quality of Life Questionnaire Associated CLL Module (QLQ-CLL16) Multi-Item Scales Score
timeFrame: Baseline, D1 of Cycles 1, 2, 3, 4, 5, 6, STC/EW visit (up to C6D28), EoCTR visit (8 to 12 weeks after C6D1), and FUVs (every 12 weeks after EoCTR up to 3 years); Cycle length = 28 days
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From signing of informed consent form up to approximately 8 years 5 months
measure: Number of Participants With Grade 3 or Higher Tumor Lysis Syndrome (TLS) and Infusion-related Reactions (IRRs)
timeFrame: From signing of informed consent form up to approximately 8 years 5 months
Other outcomes:
measure: Change From Baseline in Lymphocyte Subset Counts at Specified Time Points
timeFrame: Baseline, C4D14-28, Study Treatment Completion/Early Withdrawal (STC/EW, up to C6D28), EoCTR visit (8 to 12 weeks after C6D1), and at FUVs (every 12 weeks after EoCTR up to 3 years); Cycle length = 28 days
Locations:
city: La Jolla
country: United States
facility: University of California San Diego Medical Center
state: California
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center; Clinical Trials Office
state: New York
city: New York
country: United States
facility: Perlmutter Cancer Center NYU Langone Health
state: New York
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute; University of Utah
state: Utah
city: Garran
country: Australia
facility: The Canberra Hospital
state: Australian Capital Territory
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Kogarah, New South Wales
country: Australia
facility: St George Hospital
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Frankston
country: Australia
facility: Frankston Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Monash Medical Centre; Haematology
state: Victoria
city: Mount Waverley
country: Australia
facility: Slade Health Pharmacy
state: Victoria
city: North Melbourne
country: Australia
facility: Peter MacCallum Cancer Center
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Nedlands
country: Australia
facility: The Perth Blood Institute
state: Western Australia
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Salzburg
country: Austria
facility: LKH - Universitätsklinikum der PMU Salzburg
city: Wien
country: Austria
facility: Medizinische Universität Wien
city: Wien
country: Austria
facility: Klinik Ottakring
city: Antwerpen
country: Belgium
facility: ZNA Antwerpen; Department Hematology
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc; Hematology
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Leuven
country: Belgium
facility: UZ Leuven; Department Hematology
city: Mont-godinne
country: Belgium
facility: CHU UCL Mont-Godinne
city: Roeselare
country: Belgium
facility: AZ Delta (Campus Rumbeke)
city: Calgary
country: Canada
facility: Foothills Medical Centre; Centre Dept of Medical Clinical Neuroscience
state: Alberta
city: Hamilton
country: Canada
facility: Juravinski Cancer Clinic
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatoon City Hospital;Saskatchewan Cancer Centre
state: Saskatchewan
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Olomouc
country: Czechia
facility: Fakultní nemocnice Olomouc
city: Ostrava - Poruba
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Praha
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady
city: Herlev
country: Denmark
facility: Herlev Hospital
city: København Ø
country: Denmark
facility: Rigshospitalet
city: Odense C
country: Denmark
facility: Odense Universitetshospital
city: Roskilde
country: Denmark
facility: Sjællands Universitetshospital, Roskilde
city: Vejle
country: Denmark
facility: Sygehus Lillebælt, Vejle
city: Brest
country: France
facility: Hôpital Morvan
city: La Roche sur Yon
country: France
facility: Centre Hospitalier Départemental Les Oudairies
city: Lille
country: France
facility: Hopital Claude Huriez - CHU Lille
city: Montpellier
country: France
facility: Hopital Saint Eloi
city: Nantes
country: France
facility: CHU Nantes - Hôtel Dieu; Service Assistance Medicale à la Procreation
city: Paris
country: France
facility: Hopital Robert Debre
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Poitiers
country: France
facility: CHU Poitiers - Hopital La Miletrie
city: Rennes
country: France
facility: CHU de Rennes - Hopital de Pontchaillo
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Toulouse
country: France
facility: Institut Universitaire du Cancer - Oncopole Toulouse (IUCT-O)
city: Tours
country: France
facility: CHU Tours - Hôpital Bretonneau
city: Vandoeuvre-les-nancy
country: France
facility: Hôpital de Brabois Adultes
city: Dresden
country: Germany
facility: Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Központ; B?rgyógyászati Klinika
city: Pecs
country: Hungary
facility: Somogy Megyei Kaposi Mor Oktato Korhaz
city: Szeged
country: Hungary
facility: Szegedi Tud.Egyetem Szent-Gyorgyi Albert Klin.Kozp.
city: Torino
country: Italy
facility: Azienda Ospedaliera Città della Salute e della Scienza di Torino; Radiology
state: Abruzzo
city: Genova
country: Italy
facility: Azienda Ospedaliero Universitaria San Martino
state: Liguria
city: Bergamo
country: Italy
facility: Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)
state: Lombardia
city: Milano
country: Italy
facility: Ospedale San Raffaele
state: Lombardia
city: Milano
country: Italy
facility: Asst Grande Ospedale Metropolitano Niguarda; SC Farmacia Ospedale
state: Lombardia
city: Torrette Di Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti
state: Marche
city: Bari
country: Italy
facility: Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari
state: Puglia
city: Florence
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
state: Toscana
city: Padova
country: Italy
facility: Azienda Ospedaliera Di Padova
state: Veneto
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St. Mary?s Hospital
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, Locatie VUMC; Neurology
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC Location AMC
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis, Dordwijk; Internal Medicine, Hemato-Oncology
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum; Cardiology
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Auckland
country: New Zealand
facility: North Shore Hospital; Haematolgy
city: Auckland
country: New Zealand
facility: Middlemore Hospital
city: Christchurch
country: New Zealand
facility: Christchurch Hospital NZ
city: Mount Wellington
country: New Zealand
facility: Baxter Healthcare
city: Chorzow
country: Poland
facility: SP ZOZ Zespol Szpitali Miejskich w Chorzowie
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Lodz
country: Poland
facility: Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
city: Opole
country: Poland
facility: Szpital Wojewodzki w Opolu
city: Warszawa
country: Poland
facility: MTZ Clinical Research Sp. z o.o.
city: Zabrze
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 1
city: Moscow
country: Russian Federation
facility: FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"
state: Moskovskaja Oblast
city: Sankt-peterburg
country: Russian Federation
facility: SRI of Hematology and Transfusiology
state: Sankt Petersburg
city: St. Petersburg
country: Russian Federation
facility: North-West Federal Medical Research Center n.a. V.A. Almazov
state: Sankt Petersburg
city: Kemerovo
country: Russian Federation
facility: Kemerovo Regional Clinical Hospital
city: Omsk
country: Russian Federation
facility: BHI of Omsk region Clinical Oncology Dispensary
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona; Hematology
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
city: Lund
country: Sweden
facility: Skånes Universitetssjukhus
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology centre
city: Manchester
country: United Kingdom
facility: The Christie
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Swansea
country: United Kingdom
facility: Singleton Hospital; Pharmacy Department
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Badawi M, Chen X, Marroum P, Suleiman AA, Mensing S, Koenigsdorfer A, Schiele JT, Palenski T, Samineni D, Hoffman D, Menon R, Salem AH. Bioavailability Evaluation of Venetoclax Lower-Strength Tablets and Oral Powder Formulations to Establish Interchangeability with the 100 mg Tablet. Clin Drug Investig. 2022 Aug;42(8):657-668. doi: 10.1007/s40261-022-01172-4. Epub 2022 Jul 13.
citation: Seymour JF, Kipps TJ, Eichhorst BF, D'Rozario J, Owen CJ, Assouline S, Lamanna N, Robak T, de la Serna J, Jaeger U, Cartron G, Montillo M, Mellink C, Chyla B, Panchal A, Lu T, Wu JQ, Jiang Y, Lefebure M, Boyer M, Kater AP. Enduring undetectable MRD and updated outcomes in relapsed/refractory CLL after fixed-duration venetoclax-rituximab. Blood. 2022 Aug 25;140(8):839-850. doi: 10.1182/blood.2021015014.
citation: Kater AP, Wu JQ, Kipps T, Eichhorst B, Hillmen P, D'Rozario J, Assouline S, Owen C, Robak T, de la Serna J, Jaeger U, Cartron G, Montillo M, Dubois J, Eldering E, Mellink C, Van Der Kevie-Kersemaekers AM, Kim SY, Chyla B, Punnoose E, Bolen CR, Assaf ZJ, Jiang Y, Wang J, Lefebure M, Boyer M, Humphrey K, Seymour JF. Venetoclax Plus Rituximab in Relapsed Chronic Lymphocytic Leukemia: 4-Year Results and Evaluation of Impact of Genomic Complexity and Gene Mutations From the MURANO Phase III Study. J Clin Oncol. 2020 Dec 1;38(34):4042-4054. doi: 10.1200/JCO.20.00948. Epub 2020 Sep 28.
citation: Kater AP, Seymour JF, Hillmen P, Eichhorst B, Langerak AW, Owen C, Verdugo M, Wu J, Punnoose EA, Jiang Y, Wang J, Boyer M, Humphrey K, Mobasher M, Kipps TJ. Fixed Duration of Venetoclax-Rituximab in Relapsed/Refractory Chronic Lymphocytic Leukemia Eradicates Minimal Residual Disease and Prolongs Survival: Post-Treatment Follow-Up of the MURANO Phase III Study. J Clin Oncol. 2019 Feb 1;37(4):269-277. doi: 10.1200/JCO.18.01580. Epub 2018 Dec 3.
citation: Seymour JF, Kipps TJ, Eichhorst B, Hillmen P, D'Rozario J, Assouline S, Owen C, Gerecitano J, Robak T, De la Serna J, Jaeger U, Cartron G, Montillo M, Humerickhouse R, Punnoose EA, Li Y, Boyer M, Humphrey K, Mobasher M, Kater AP. Venetoclax-Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. N Engl J Med. 2018 Mar 22;378(12):1107-1120. doi: 10.1056/NEJMoa1713976.
citation: Jones AK, Freise KJ, Agarwal SK, Humerickhouse RA, Wong SL, Salem AH. Clinical Predictors of Venetoclax Pharmacokinetics in Chronic Lymphocytic Leukemia and Non-Hodgkin's Lymphoma Patients: a Pooled Population Pharmacokinetic Analysis. AAPS J. 2016 Sep;18(5):1192-1202. doi: 10.1208/s12248-016-9927-9. Epub 2016 May 27.