Comparison of the Treatments of Obinutuzumab + Venetoclax Versus Obinutuzumab + Chlorambucil in Patients With Chronic Lymphocytic Leukemia

Lymphocytic Leukemia, Chronic Clinical Trial

Official title:

A Prospective, Open-Label, Multicenter Randomized Phase III Trial to Compare The Efficacy and Safety of A Combined Regimen of Obinutuzumab and Venetoclax Versus Obinutuzumab and Chlorambucil in Previously Untreated Patients With CLL and Coexisting Medical Conditions

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02242942
• Other study ID #: BO25323
• Secondary ID: 2014-001810-24CL
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 31, 2014
• Est. completion date: August 31, 2025

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This open-label, multicenter, randomized Phase III study is designed to compare the efficacy and safety of a combined regimen of obinutuzumab and venetoclax versus obinutuzumab + chlorambucil in participants with chronic lymphocytic leukemia (CLL) and coexisting medical conditions. The time on study treatment was approximately one year and the follow-up period will be up to 9 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 445
• Est. completion date: August 31, 2025
• Est. primary completion date: August 17, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Documented previously untreated CLL according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria

• CLL requiring treatment according to IWCLL criteria

• Total Cumulative Illness Rating Scale (CIRS score) greater than (>) 6

• Adequate marrow function independent of growth factor or transfusion support within 2 weeks of screening as per protocol, unless cytopenia is due to marrow involvement of CLL

• Adequate liver function

• Life expectancy > 6 months

• Agreement to use highly effective contraceptive methods per protocol

Exclusion Criteria:

• Transformation of CLL to aggressive Non-Hodgkin's lymphoma (Richter's transformation or pro-lymphocytic leukemia)

• Known central nervous system involvement

• Participants with a history of confirmed progressive multifocal leukoencephalopathy (PML)

• An individual organ/ system impairment score of 4 as assessed by the CIRS definition limiting the ability to receive the treatment regimen of this trial with the exception of eyes, ears, nose, throat organ system

• Participants with uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia

• Inadequate renal function

• History of prior malignancy, except for conditions as listed in the protocol if participants have recovered from the acute side effects incurred as a result of previous therapy

• Use of investigational agents or concurrent anti-cancer treatment within the last 4 weeks of registration

• Participants with active bacterial, viral, or fungal infection requiring systemic treatment within the last two months prior to registration

• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products

• Hypersensitivity to chlorambucil, obinutuzumab, or venetoclax or to any of the excipients

• Pregnant women and nursing mothers

• Positive test results for chronic hepatitis B virus (HBV) infection (defined as positive hepatitis B surface antigen [HBsAg] serology) or positive test result for hepatitis C (hepatitis C virus [HCV] antibody serology testing)

• Participants with known infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus-1 (HTLV-1)

• Requires the use of warfarin, marcumar, or phenprocoumon

• Received agents known to be strong and moderate Cytochrome P450 3A inhibitors or inducers within 7 days prior to the first dose of study drug

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphocytic Leukemia, Chronic

Intervention

Drug:
• Chlorambucil
Chlorambucil 0.5 milligrams per kilogram (mg/kg) orally at Day 1 and Day 15 at of each 28 day cycle for 12 cycles.
• Venetoclax
Venetoclax, oral tablet: 20 mg daily during Cycle 1, Day 22-28; 50 mg daily during Cycle 2, Day 1-7; 100 mg daily during Cycle 2, Day 8-14; 200 mg daily during Cycle 2, Day 15-21; 400 mg daily during Cycle 2, Day 22-28 and on Day 1-28 for all subsequent cycles until the end of Cycle 12.
• Obinutuzumab
Obinutuzumab, IV infusion: 100 mg or 1000 mg, depending on splitting rules, at Cycle 1, Day 1 (if 100 mg was received on Day 1, 900 mg will be administered on Cycle 1, Day 2); 1000 mg at Cycle 1, Day 8 and Day 15; 1000 mg at Day 1 for all subsequent cycles until the end of Cycle 6

Locations

Country	Name	City	State
Argentina	Hospital Italiano	Buenos Aires
Australia	Royal Adelaide Hospital; Haematology Clinical Trials	Adelaide	South Australia
Australia	Ashford Cancer Centre Research; Internal Medicine/Medical Oncology	Ashford	South Australia
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	The Townsville Hospital	Douglas	Queensland
Australia	The Northern Hospital	Epping	Victoria
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Monash Medical Centre; Haematology	Melbourne	Victoria
Australia	Tweed Hospital	Tweed Heads	New South Wales
Australia	Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology	Woolloongabba	Queensland
Austria	Tiroler Landeskrankenanstalten Ges.M.B.H.; Innere Medizin Abt. Für Hämatologie & Onkologie	Innsbruck
Austria	Hanusch-Krankenhaus; Iii. Medizinische Abt.	Wien
Austria	Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Hämatologie & Hämostaseologie	Wien
Austria	Wilhelminenspital; I. Medizinische Abt.	Wien
Brazil	Hospital das Clinicas - UFRGS	Porto Alegre	RS
Brazil	Hospital das Clinicas - FMUSP	Sao Paulo	SP
Brazil	Hospital Santa Marcelina	Sao Paulo	SP
Brazil	Hospital Sírio-Libanês	Sao Paulo	SP
Brazil	Instituto de Ensino e Pesquisa Sao Lucas - IEP	Sao Paulo	SP
Bulgaria	UMHAT Dr Georgi Stranski; Hematology	Pleven
Bulgaria	UMHAT " Sveti Georgi" Plovdiv - Clinic of Oncology and Hematology	Plovdiv
Bulgaria	University Hospital Sv.Georgi Clnic of Hematology; Hematology	Plovdiv
Bulgaria	University Multiprofile Hospital For Active Treatment "Sveti Ivan Rilski" EAD; clinical hematology	Sofia
Bulgaria	MHAT Hristo Botev; First Internal Department	Vratsa
Canada	Tom Baker Cancer Centre; Dept of Medicine	Calgary	Alberta
Canada	Queen Elizabeth II Health Sciences Centre; Oncology	Halifax	Nova Scotia
Canada	Jewish General Hospital	Montreal	Quebec
Croatia	University Hospital Center Zagreb; Haematology Department	Zagreb
Croatia	University Hospital Merkur Clinic for Internal Medicine/ Hematology	Zagreb
Denmark	Herlev Hospital	Herlev
Denmark	Rigshospitalet	København Ø
Denmark	Sjaellands Universitetshospital, Roskilde	Roskilde
Denmark	Sygehus Lillebælt, Vejle	Vejle
Estonia	North Estonia medical Centre; Hematology	Tallinn
Estonia	Tartu Uni Hospital; Hematology - Oncology Clinic	Tartu
France	CHU Besançon - Hôpital Jean Minjoz	Besançon Cedex
France	Institut d'Hématologie de Basse Normandie	Caen
France	Chu Estaing; Hematologie Clinique Adultes	Clermont Ferrand
France	Hopital Henri Mondor	Creteil
France	CHU de Dijon - Hopital le Bocage	Dijon
France	CHU de Grenoble	Grenoble
France	Centre Jean Bernard	Le Mans
France	Centre Leon Berard; Departement Oncologie Medicale	Lyon
France	Hôpital Saint Eloi; Service d?Hématologie et Oncologie Clinique - Recherche Clinique	Montpellier
France	Hopital Hotel Dieu Et Hme;Hopital De Jour	Nantes
France	Hopital Saint Louis ; Service d Oncologie Medicale Fougere 6 (Pr Misset)	Paris
France	Hopital Pontchaillou; Hematologie Clinique	Rennes
France	Centre Henri Becquerel; Hematologie	Rouen
France	CH de Toulon Hôpital Sainte Musse	Toulon
France	Institut Gustave Roussy - Hematologie	Villejuif
Germany	Uniklinik RWTH Aachen; Klinik IV; Klinik Hämatologie, Onkologie, Hämostaseologie und Stamm.	Aachen
Germany	Gesundheitszentrum St. Marien GmbH; Med. II, Hämatologie/Onkologie	Amberg
Germany	Charite - Campus Virchow-Klinikum	Berlin
Germany	Charite - Universitätsmedizin Berlin	Berlin
Germany	BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie-Onkologie	Dresden
Germany	Uniklinikum "Carl Gustav Carus"; Med. Klinik 1; Hämatologie, Zelltherapie und Medizinische Onkologie	Dresden
Germany	Universitätsklinikum Essen; Klinik für Hämatologie	Essen
Germany	Klinik Esslingen; Klinik für Allgemeine Innere Medizin, Onkologie/Haematologie	Esslingen
Germany	Klinikum Frankfurt/Oder	Frankfurt/Oder
Germany	Uniklinikum Freiburg	Freiburg
Germany	Uni Göttingen, Georg-August-Universität; Klinik für Hämatologie und Medizinische Onkologie	Göttingen
Germany	Universitaetsklinikum Heidelberg	Heidelberg
Germany	Stiftung Kathol. Krankenhaus Marienhospital Herne Klinik Mitte	Herne
Germany	Praxisklinik für Hämatologie und Onkologie Koblenz	Koblenz
Germany	Universitätsklinikum Köln; Innere Medizin I; Onkologie, Hämatologie	Köln
Germany	Tagesklinik Landshut; Hämatologie/Onkologie	Landshut
Germany	Kliniken Maria Hilf GmbH Innere Medizin I	Mönchengladbach
Germany	Klinikum rechts der Isar der Technischen Universität München	Munchen
Germany	Klinikum der Universität München, Campus Großhadern; Medizinische Klinik und Poliklinik III	München
Germany	München Klinik Schwabing; Klinik für Hämatologie, Onkologie, Immunologie	München
Germany	Klinikum Schwäbisch Gmünd	Mutlangen
Germany	Gemeinschaftspraxis Dr. med. Holger Klaproth	Neunkirchen/Saar
Germany	Brüderkrankenhaus St. Josef Paderborn	Paderborn
Germany	Krankenhaus Barmherzige Bruder Regensburg	Regensburg
Germany	Marienhospital	Stuttgart
Germany	Robert-Bosch-Krankenhaus	Stuttgart
Germany	Universitätsklinikum Tübingen	Tübingen
Germany	Universtitätsklinikum Ulm; Klinik für Innere Medizin III	Ulm
Germany	Medizinisches Versorgungszentrum Nuklearmedizin-Strahlentherapie-Onkologie	Weiden
Italy	Arcispedale S. Anna; Sezione Di Ematologia	Ferrara	Emilia-Romagna
Italy	Ospedali Riuniti Papardo-Piemonte; Struttura Complessa Di Ematologia	Messina	Lazio
Italy	Ospedale San Raffaele	Milano	Lombardia
Italy	Uni Cattolica; Divisione Di Ematologia	Roma	Lazio
Italy	Az. Osp. S. Maria; Dept. Di Oncologia Medica	Terni	Umbria
Italy	AOU Città della Salute e della Scienza di Torino - Presidio Le Molinette	Torino	Lazio
Italy	Ospedale dell' Angelo; U.O. Ematologia	Venezia Mestre	Veneto
Mexico	Hospital General de Culiacan	Culiacan	Sinaloa
New Zealand	Canterbury Health Laboratories; Haematology	Christchurch
New Zealand	Dunedin Hospital	Dunedin
New Zealand	Midcentral District Health Board	Palmerston North
New Zealand	Wellington Hospital	Wellington
Poland	Uniwersytecki Szpital Kliniczny w Bia?ymstoku, Klinika Hematologii z Pododdzia?em Chorob Naczyn	Bialystok
Poland	Samodzielny Public Zaklad	Chorzów
Poland	Wojewódzki Szpital Specjalistyczny im.Miko?ajaKopernika;KlinikaHematologiiUniwersytetuMedycznego	Lodz
Poland	Wojewodzki Szpital Specjalistyczny im. J. Korczaka; Oddzia? Chorób Wewnetrznych/Hematologiczny	Slupsk
Poland	Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroc?awiu; Klinika Hematologii	Wroclaw
Romania	Fundeni Clinical Inst. ; Hematology Dept	Bucharest
Romania	Institutul Regional de Oncologie Iasi; Clinica de Hematologie	Iasi
Romania	Spitalul Clinic Judetean de Urgenta Targu-Mures; compartiment Hematologie	Targu-mures
Russian Federation	Republican Clinical Oncologic Dispensary of Republic Of Tatarstan	Kazan	Tatarstan
Russian Federation	Moscow State Budgetary Healthcare Institution	Moscow	Moskovskaja Oblast
Russian Federation	Regional Clinical Hospital N.A. Semashko; Hematology	Nizhny Novgorod	Niznij Novgorod
Russian Federation	Penza Regional Oncology Dispensary	Penza
Russian Federation	Clinical MSCh No1	Perm
Russian Federation	Rostov State Medical Uni ; Hematology	Rostov-na-donu	Rostov
Russian Federation	SBEI of HPE ?Bashkir State Medical University? of MoH RF	UFA	Baskortostan
Spain	Hospital Clínic i Provincial; Servicio de Hematología y Oncología	Barcelona
Spain	Hospital del Mar; Servicio de Hematologia	Barcelona
Spain	Hospital Universitari Vall d'Hebron; Servicio de Hematologia	Barcelona
Spain	Hospital Universitario de Canarias;servicio de Hematologia	La Laguna	Tenerife
Spain	Hospital Univ. 12 de Octubre; Servicio de Hematologia	Madrid
Spain	Hospital Universitario de la Princesa; Servicio de Hematologia	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Complejo Hospitalario de Navarra	Pamplona	Navarra
Spain	Hospital Clinico Universitario de Salamanca;Servicio de Hematologia	Salamanca
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Complejo Hospitalario de Toledo- H. Virgen de la Salud; Servicio de Hematología	Toledo
Spain	Hospital Arnau de Vilanova (Valencia) Servicio de Hematologia	Valencia
Spain	Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia	Valencia
Switzerland	Inselspital Bern; Hämatologie und Hämatologisches Zentrallabor	Bern
Switzerland	Luzerner Kantonsspital, Hämatologie	Luzern
Switzerland	Universitätsspital Zürich Medizin Hämatologie; Klinik für Hämatologie	Zürich
United Kingdom	Birmingham Heartlands Hospital	Birmingham
United Kingdom	Boston Pilgrim Hospital	Boston,Lincolnshire
United Kingdom	Western General Hospital; Department of Haematology	Edinburgh
United Kingdom	Lincoln County Hospital	Lincoln
United Kingdom	University Hospital Southampton NHS Foundation Trust	Southhampton
United States	Winship Cancer Institute	Atlanta	Georgia
United States	Henry Ford Hospital	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	San Diego Pacific Hematology Assocates	Encinitas	California
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	UC San Diego Health System	La Jolla	California
United States	Joe Arrington Cancer Center	Lubbock	Texas
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (3)

Lead Sponsor	Collaborator
Hoffmann-La Roche	AbbVie, German CLL Study Group

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Brazil,  Bulgaria,  Canada,  Croatia,  Denmark,  Estonia,  France,  Germany,  Italy,  Mexico,  New Zealand,  Poland,  Romania,  Russian Federation,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS) Based on Investigator Assessment According to IWCLL Criteria	PFS was determined according to IWCLL 2008 criteria and defined as the time from randomization to the first occurrence of PD or death from any cause. Disease progression was characterized by at least one of the following: 1) >/= 50% increase in the absolute number of circulating lymphocytes to at least 5*10^9/L, 2) Appearance of new palpable lymph nodes (> 15 mm in longest diameter) or any new extra-nodal lesion; 3) >/= 50% increase in the longest diameter of any previous site of lymphadenopathy; 4) >/= 50% increase in the enlargement of the liver and/or spleen; 5) Transformation to a more aggressive histology.	Baseline until disease progression or death up to approximately 3.75 years
Secondary	Progression Free Survival (PFS) Based on Institutional Review Committee (IRC)-Assessments According to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria	PFS was determined according to IWCLL 2008 criteria and defined as the time from randomization to the first occurrence of progressive disease (PD) or death from any cause. Disease progression was characterized by at least one of the following: 1) >/= 50% increase in the absolute number of circulating lymphocytes to at least 5*10^9/L, 2) Appearance of new palpable lymph nodes (> 15 mm in longest diameter) or any new extra-nodal lesion; 3) >/= 50% increase in the longest diameter of any previous site of lymphadenopathy; 4) >/= 50% increase in the enlargement of the liver and/or spleen; 5) Transformation to a more aggressive histology.	Baseline until disease progression or death up to approximately 3.75 years
Secondary	Percentage of Participants With an Overall Response (OR) at Completion of Treatment, as Determined by the Investigator According to IWCLL Criteria	OR was defined as complete response (CR), CR with incomplete bone marrow recovery (CRi), or partial response (PR) according to IWCLL 2008 criteria. CR requires all of the following: peripheral blood lymphocytes below 4x10^9/L, absence of lymphadenopathy by physical examination and computed tomography (CT) scan, no hepatomegaly or splenomegaly, absence of disease or constitutional symptoms, blood counts of neutrophils >1.5*10^9/L, platelets >100*10^9/L and hemoglobin >110 g/L, bone marrow at least normocellular for age without clonal infiltrate (except for Cri). PR: two of the following features for at least 2 months: >/= 50% decrease in peripheral blood lymphocyte count from the pretreatment value, >/=50% reduction in lymphadenopathy, >/=50% reduction of liver and/or spleen enlargement, and at least one of the following blood counts: neutrophils >1.5*10^9/L, platelets >100*10^9/L and hemoglobin >110 g/L.	At the completion of treatment assessment 3 months after treatment completion (at approximately 15 months)
Secondary	Percentage of Participants With a Complete Response Rate (CRR) at the Completion of Treatment Assessment as Determined by the Investigator According to IWCLL Criteria	CRR was defined as the rate of a clinical response of CR or CRi according to IWCLL 2008 criteria. CR requires all of the following: peripheral blood lymphocytes below 4x10^9/L, absence of lymphadenopathy by physical examination and CT scan, no hepatomegaly or splenomegaly, absence of disease or constitutional symptoms, blood counts of neutrophils >1.5*10^9/L, platelets >100*10^9/L and hemoglobin >110 g/L, bone marrow at least normocellular for age without clonal infiltrate (except for Cri).	At the completion of treatment assessment 3 months after treatment completion (at approximately 15 months)
Secondary	Percentage of Participants With Minimal Residual Disease (MRD) Negativity in Peripheral Blood as Measured by Allele-Specific Oligonucleotide Polymerase Chain Reaction (ASO-PCR) at Completion of Treatment	MRD negativity was defined as having < 1 CLL cell per 10,000 leucocytes in peripheral blood.	At the completion of treatment assessment 3 months after treatment completion (at approximately 15 months)
Secondary	Percentage of Participants With MRD Negativity in Bone Marrow as Measured by ASO-PCR at Completion of Treatment	MRD negativity was defined as having < 1 CLL cell per 10,000 leucocytes in bone marrow.	At the completion of treatment assessment 3 months after treatment completion (at approximately 15 months)
Secondary	Overall Survival (OS)	OS was defined as the time between the date of randomization and the date of death due to any cause.	Baseline until death, up to approximately 10.75 years
Secondary	Percentage of Participants With MRD Negativity in Peripheral Blood as Measured by ASO-PCR at Completion of Combination Treatment Assessment	MRD negativity was defined as having < 1 CLL cell per 10,000 leucocytes in peripheral blood.	Day 1 Cycle 9 or 3 months after last IV infusion, approximately 9 months
Secondary	Percentage of Participants With MRD Negativity in Bone Marrow as Measured by ASO-PCR at Completion of Combination Treatment Assessment	MRD negativity was defined as having < 1 CLL cell per 10,000 leucocytes in bone marrow.	Day 1 Cycle 9 or 3 months after last IV infusion at approximately 9 months
Secondary	Percentage of Participants With OR at Completion of Combination Treatment Response Assessment	OR was defined as CR, CRi or PR according to IWCLL 2008 criteria. CR required all of the following: peripheral blood lymphocytes below 4x10^9/L, absence of lymphadenopathy by physical examination, no hepatomegaly or splenomegaly, absence of disease or constitutional symptoms, blood counts of neutrophils >1.5*10^9/L, platelets >100*10^9/L and hemoglobin >110 g/L. PR: two of the following features for at least 2 months: >/= 50% decrease in peripheral blood lymphocyte count from the pretreatment value, >/=50% reduction in lymphadenopathy, >/=50% reduction of liver and/or spleen enlargement, and at least one of the following blood counts: neutrophils >1.5*10^9/L, platelets >100*10^9/L and hemoglobin >110 g/L.	Day 1 Cycle 7 or 28 days after last IV infusion, approximately 6 months
Secondary	Duration of Objective Response (DOR)	PD was defined as lymphadenopathy, >=50% increase in liver or spleen size, >=50% increase in lymphocyte count, transformation to a more aggressive histology or occurrence of cytopenia.	Time from the first occurrence of a documented objective response to the time of PD as determined by the investigator or death from any cause, up to approximately 10.75 years
Secondary	Percentage of Participants By Best Response Achieved (CR, CRi, PR, Stable Disease (SD), or PD)	CR: peripheral blood lymphocytes below 4x10^9/L, absence of lymphadenopathy by physical examination and CT scan, no hepatomegaly or splenomegaly, absence of disease or constitutional symptoms, blood counts of neutrophils >1.5*10^9/L, platelets >100*10^9/L and hemoglobin >110 g/L, bone marrow at least normocellular for age without clonal infiltrate (except for Cri). PR: any two for at least 2 months: >/= 50% decrease in peripheral blood lymphocyte count from the pretreatment value, >/=50% reduction in lymphadenopathy, >/=50% reduction of liver and/or spleen enlargement, and at least one of the following blood counts: neutrophils >1.5*10^9/L, platelets >100*10^9/L and hemoglobin >110 g/L. PD: lymphadenopathy, >=50% increase in liver or spleen size, >=50% increase in lymphocyte count, transformation to a more aggressive histology or occurrence of cytopenia. SD: a non-response and used to characterize participants who did not achieve a CR or a PR, and who have not exhibited PD.	Baseline up to the completion of treatment assessment 3 months after treatment completion (up to approximately 15 months)
Secondary	Event-Free Survival		Time between date of randomization and the date of disease progression/relapse on the basis of investigator-assessment, death, or start of a new anti-leukemic therapy, up to 10.75 years
Secondary	Time to Next Anti-Leukemic Treatment		Time between the date of randomization and the date of first intake of new anti-leukemic therapy, up to 10.75 years
Secondary	Number of Participants With Adverse Events (AEs)	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs.	Up to approximately 10.75 years
Secondary	Percentage of Participants With CD19 + /CD5+ B Cells or CD14+ Monocytes		Baseline up to approximately 10.75 years
Secondary	Percentage of Participants With Human-Anti-Human Antibodies		Baseline up to approximately 10.75 years
Secondary	Percentage of Participants Recorded as Premature Study Withdrawals		Up to approximately 10.75 years
Secondary	Plasma Concentrations of Venetoclax		Pre-venetoclax dose (0 hour) and 4 hours post- venetoclax dose on Day 1 Cycle 4
Secondary	Serum Concentrations of Obinutuzumab		Pre-obinutuzumab infusion (0 hour) and end of obinutuzumab infusion on Day 1 Cycle 4
Secondary	Change From Baseline in M.D. Anderson Symptom Inventory-CLL (MDASI-CLL) Score	The MDASI-CLL is a questionnaire of 25 items related to CLL specific symptoms that a participant may have experienced in the past 24 hours. Participants were asked to rate the severity of 13 symptoms called mean core symptom severity (i.e., pain, fatigue, nausea, disturbed sleep, distressed, shortness of breath, remembering things, lack of appetite, drowsy, dry mouth, sadness, vomiting, and numbness or tingling), 6 disease-specific symptoms called mean module symptom severity (night sweats, fevers and chills, lymph node swelling, diarrhea, easy bruising or bleeding, and constipation) and 6 mean interference on life questions (i.e., general activity, walking, work, mood, relations with other people, and enjoyment of life) on a scale from 0 to 10 with 0 indicating that the symptom is "not present" or "did not interfere" with the participant's activities and 10 indicating "as bad as you can imagine" or "interfered completely". Scores were averaged (range 0 to 10) for each of three parts.	Baseline up to approximately 10.75 years
Secondary	Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQC30)	The EORTC QLQ-C30 is a validated and reliable self-report measure consisting of 30 questions incorporated into five functional scales (physical, role, cognitive, emotional, and social scales), three symptom scales (fatigue, pain, nausea, and vomiting scales), and a global health status/global quality-of-life scale. The remaining single items (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) assess the additional symptoms experienced by patients with cancer and the perceived financial burden of treatment. The 28 function and symptom items were scored on a 4-point scale that ranged from "not at all" to "very much," and the 2 global health status/global quality-of-life items were scored on a 7-point scale that ranged from "very poor" to "excellent." Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e., higher functioning, higher symptom severity).	Baseline up to approximately 10.75 years
Secondary	Change From Baseline in EuroQol 5 Dimension Questionnaire (EQ-5D-3L)	The EQ-5D-3L questionnaire is a generic, preference based health utility measure that assesses 5 health states (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and is used to build a composite of the patient's health status. The EQ-5D-3L was employed in this study to calculate health utilities for economic modeling, which ranged 0-1. The EQ-5D-3L also contained a visual analog scale (VAS) to assess the participant's overall health, which ranged from 0-100 with a higher score indicating a worse health status.	Baseline up to approximately 10.75 years