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

• ClinicalTrials.gov Identifier: NCT02242942
• Recruitment Status: Active, not recruiting
• First Posted: September 17, 2014
• Results First Posted: October 1, 2019
• Last Update Posted: December 23, 2022
• Sponsor: Hoffmann-La Roche
• Collaborators: AbbVie; German CLL Study Group
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Lymphocytic Leukemia, Chronic	Drug: Chlorambucil; Drug: Venetoclax; Drug: Obinutuzumab	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 445 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: December 31, 2014
• Actual Primary Completion Date: August 17, 2018
• Estimated Study Completion Date: August 31, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Safety Run-in Obinutuzumab + Venetoclax; Subjects received obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles comprised of 28 days.	Drug: 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.; Other Name: ABT-0199, GDC-0199; Drug: 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; Other Name: GA-101; Gazyva
Experimental: Obinutuzumab + Chlorambucil; Participants will receive obinutuzumab for 6 cycles and chlorambucil for 12 cycles. Cycles will comprise 28 days.	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.; Drug: 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; Other Name: GA-101; Gazyva
Experimental: Obinutuzumab + Venetoclax; Participants will receive obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles will comprise 28 days.	Drug: 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.; Other Name: ABT-0199, GDC-0199; Drug: 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; Other Name: GA-101; Gazyva

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival (PFS) Based on Investigator Assessment According to IWCLL Criteria [ Time Frame: Baseline until disease progression or death up to approximately 3.75 years ]
   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.

Secondary Outcome Measures :

1. Progression Free Survival (PFS) Based on Institutional Review Committee (IRC)-Assessments According to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria [ Time Frame: Baseline until disease progression or death up to approximately 3.75 years ]
   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.
2. Percentage of Participants With an Overall Response (OR) at Completion of Treatment, as Determined by the Investigator According to IWCLL Criteria [ Time Frame: At the completion of treatment assessment 3 months after treatment completion (at approximately 15 months) ]
   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.
3. Percentage of Participants With a Complete Response Rate (CRR) at the Completion of Treatment Assessment as Determined by the Investigator According to IWCLL Criteria [ Time Frame: At the completion of treatment assessment 3 months after treatment completion (at approximately 15 months) ]
   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).
4. 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 [ Time Frame: At the completion of treatment assessment 3 months after treatment completion (at approximately 15 months) ]
   MRD negativity was defined as having < 1 CLL cell per 10,000 leucocytes in peripheral blood.
5. Percentage of Participants With MRD Negativity in Bone Marrow as Measured by ASO-PCR at Completion of Treatment [ Time Frame: At the completion of treatment assessment 3 months after treatment completion (at approximately 15 months) ]
   MRD negativity was defined as having < 1 CLL cell per 10,000 leucocytes in bone marrow.
6. Overall Survival (OS) [ Time Frame: Baseline until death, up to approximately 10.75 years ]
   OS was defined as the time between the date of randomization and the date of death due to any cause.
7. Percentage of Participants With MRD Negativity in Peripheral Blood as Measured by ASO-PCR at Completion of Combination Treatment Assessment [ Time Frame: Day 1 Cycle 9 or 3 months after last IV infusion, approximately 9 months ]
   MRD negativity was defined as having < 1 CLL cell per 10,000 leucocytes in peripheral blood.
8. Percentage of Participants With MRD Negativity in Bone Marrow as Measured by ASO-PCR at Completion of Combination Treatment Assessment [ Time Frame: Day 1 Cycle 9 or 3 months after last IV infusion at approximately 9 months ]
   MRD negativity was defined as having < 1 CLL cell per 10,000 leucocytes in bone marrow.
9. Percentage of Participants With OR at Completion of Combination Treatment Response Assessment [ Time Frame: Day 1 Cycle 7 or 28 days after last IV infusion, approximately 6 months ]
   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.
10. Duration of Objective Response (DOR) [ Time Frame: 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 ]
    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.
11. Percentage of Participants By Best Response Achieved (CR, CRi, PR, Stable Disease (SD), or PD) [ Time Frame: Baseline up to the completion of treatment assessment 3 months after treatment completion (up to approximately 15 months) ]
    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.
12. Event-Free Survival [ Time Frame: 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 ]
13. Time to Next Anti-Leukemic Treatment [ Time Frame: Time between the date of randomization and the date of first intake of new anti-leukemic therapy, up to 10.75 years ]
14. Number of Participants With Adverse Events (AEs) [ Time Frame: Up to approximately 10.75 years ]
    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.
15. Percentage of Participants With CD19 + /CD5+ B Cells or CD14+ Monocytes [ Time Frame: Baseline up to approximately 10.75 years ]
16. Percentage of Participants With Human-Anti-Human Antibodies [ Time Frame: Baseline up to approximately 10.75 years ]
17. Percentage of Participants Recorded as Premature Study Withdrawals [ Time Frame: Up to approximately 10.75 years ]
18. Plasma Concentrations of Venetoclax [ Time Frame: Pre-venetoclax dose (0 hour) and 4 hours post- venetoclax dose on Day 1 Cycle 4 ]
19. Serum Concentrations of Obinutuzumab [ Time Frame: Pre-obinutuzumab infusion (0 hour) and end of obinutuzumab infusion on Day 1 Cycle 4 ]
20. Change From Baseline in M.D. Anderson Symptom Inventory-CLL (MDASI-CLL) Score [ Time Frame: Baseline up to approximately 10.75 years ]
    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.
21. Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQC30) [ Time Frame: Baseline up to approximately 10.75 years ]
    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).
22. Change From Baseline in EuroQol 5 Dimension Questionnaire (EQ-5D-3L) [ Time Frame: Baseline up to approximately 10.75 years ]
    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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

City of Hope

Duarte, California, United States, 91010

San Diego Pacific Hematology Assocates

Encinitas, California, United States, 92024-1375

UC San Diego Health System

La Jolla, California, United States, 92093

United States, Colorado

Banner MD Anderson Cancer Center

Greeley, Colorado, United States, 85234

United States, Florida

Moffitt Cancer Center

Tampa, Florida, United States, 33612

United States, Georgia

Winship Cancer Institute

Atlanta, Georgia, United States, 30322

United States, Illinois

Ingalls Memorial Hospital

Harvey, Illinois, United States, 60426

United States, Michigan

Henry Ford Hospital

Detroit, Michigan, United States, 48202

United States, Texas

Joe Arrington Cancer Center

Lubbock, Texas, United States, 79410

Argentina

Hospital Italiano

Buenos Aires, Argentina, C1181ACH

Australia, New South Wales

Liverpool Hospital

Sydney, New South Wales, Australia, 2080

Tweed Hospital

Tweed Heads, New South Wales, Australia, 2485

Australia, Queensland

The Townsville Hospital

Douglas, Queensland, Australia, 4814

Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology

Woolloongabba, Queensland, Australia, 4102

Australia, South Australia

Royal Adelaide Hospital; Haematology Clinical Trials

Adelaide, South Australia, Australia, 5000

Ashford Cancer Centre Research; Internal Medicine/Medical Oncology

Ashford, South Australia, Australia, 5035

Australia, Victoria

Box Hill Hospital

Box Hill, Victoria, Australia, 3128

The Northern Hospital

Epping, Victoria, Australia, VIC 3076

Monash Medical Centre; Haematology

Melbourne, Victoria, Australia, 3168

Austria

Tiroler Landeskrankenanstalten Ges.M.B.H.; Innere Medizin Abt. Für Hämatologie & Onkologie

Innsbruck, Austria, 6020

Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Hämatologie & Hämostaseologie

Wien, Austria, 1090

Hanusch-Krankenhaus; Iii. Medizinische Abt.

Wien, Austria, 1140

Wilhelminenspital; I. Medizinische Abt.

Wien, Austria, 1160

Brazil

Hospital das Clinicas - UFRGS

Porto Alegre, RS, Brazil, 90035-903

Instituto de Ensino e Pesquisa Sao Lucas - IEP

Sao Paulo, SP, Brazil, 01236-030

Hospital Sírio-Libanês

Sao Paulo, SP, Brazil, 01308-050

Hospital das Clinicas - FMUSP

Sao Paulo, SP, Brazil, 05403-900

Hospital Santa Marcelina

Sao Paulo, SP, Brazil, 08270-070

Bulgaria

UMHAT Dr Georgi Stranski; Hematology

Pleven, Bulgaria, 5800

UMHAT " Sveti Georgi" Plovdiv - Clinic of Oncology and Hematology

Plovdiv, Bulgaria, 4002

University Hospital Sv.Georgi Clnic of Hematology; Hematology

Plovdiv, Bulgaria, 4002

University Multiprofile Hospital For Active Treatment "Sveti Ivan Rilski" EAD; clinical hematology

Sofia, Bulgaria, 1431

MHAT Hristo Botev; First Internal Department

Vratsa, Bulgaria, 3000

Canada, Alberta

Tom Baker Cancer Centre; Dept of Medicine

Calgary, Alberta, Canada, T2N 4N2

Canada, Nova Scotia

Queen Elizabeth II Health Sciences Centre; Oncology

Halifax, Nova Scotia, Canada, B3H 2Y9

Canada, Quebec

Jewish General Hospital

Montreal, Quebec, Canada, H3T 1E2

Croatia

University Hospital Center Zagreb; Haematology Department

Zagreb, Croatia, 10000

University Hospital Merkur Clinic for Internal Medicine/ Hematology

Zagreb, Croatia, 10000

Denmark

Herlev Hospital

Herlev, Denmark, 2730

Rigshospitalet

København Ø, Denmark, 2100

Sjællands Universitetshospital, Roskilde

Roskilde, Denmark, 4000

Sygehus Lillebælt, Vejle

Vejle, Denmark, 7100

Estonia

North Estonia medical Centre; Hematology

Tallinn, Estonia, 13419

Tartu Uni Hospital; Hematology - Oncology Clinic

Tartu, Estonia, 51014

France

CHU Besançon - Hôpital Jean Minjoz

Besançon Cedex, France, 25030

Institut d'Hématologie de Basse Normandie

Caen, France, 14000

Chu Estaing; Hematologie Clinique Adultes

Clermont Ferrand, France, 63003

Hopital Henri Mondor

Creteil, France, 94000

CHU de Dijon - Hopital le Bocage

Dijon, France, 21000

CHU de Grenoble

Grenoble, France, 38043

Centre Jean Bernard

Le Mans, France, 72015

Centre Leon Berard; Departement Oncologie Medicale

Lyon, France, 69373

Hôpital Saint Eloi; Service d'Hématologie et Oncologie Clinique - Recherche Clinique

Montpellier, France, 34295

Hopital Hotel Dieu Et Hme;Hopital De Jour

Nantes, France, 44093

Hopital Saint Louis ; Service d Oncologie Medicale Fougere 6 (Pr Misset)

Paris, France, 75475

Hopital Pontchaillou; Hematologie Clinique

Rennes, France, 35033

Centre Henri Becquerel; Hematologie

Rouen, France, 76038

CH de Toulon Hôpital Sainte Musse

Toulon, France, 83056

Institut Gustave Roussy - Hematologie

Villejuif, France, 94805

Germany

Uniklinik RWTH Aachen; Klinik IV; Klinik Hämatologie, Onkologie, Hämostaseologie und Stamm.

Aachen, Germany, 52074

Gesundheitszentrum St. Marien GmbH; Med. II, Hämatologie/Onkologie

Amberg, Germany, 92224

Charite - Universitätsmedizin Berlin

Berlin, Germany, 12203

Charite - Campus Virchow-Klinikum

Berlin, Germany, 13353

BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie-Onkologie

Dresden, Germany, 01307

Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik und Poliklinik I

Dresden, Germany, 01307

Universitätsklinikum Essen; Klinik für Hämatologie

Essen, Germany, 45122

Klinik Esslingen; Klinik für Allgemeine Innere Medizin, Onkologie/Haematologie

Esslingen, Germany, 73730

Klinikum Frankfurt/Oder

Frankfurt/Oder, Germany, 15236

Uniklinikum Freiburg

Freiburg, Germany, 79106

Uni Göttingen, Georg-August-Universität; Klinik für Hämatologie und Medizinische Onkologie

Göttingen, Germany, 37075

Universitaetsklinikum Heidelberg

Heidelberg, Germany, 69120

Stiftung Kathol. Krankenhaus Marienhospital Herne Klinik Mitte

Herne, Germany, 44625

Praxisklinik für Hämatologie und Onkologie Koblenz

Koblenz, Germany, 56068

Universitätsklinikum Köln; Innere Medizin I; Onkologie, Hämatologie

Köln, Germany, 50931

Tagesklinik Landshut; Hämatologie/Onkologie

Landshut, Germany, 84028

Klinikum rechts der Isar der Technischen Universität München

Munchen, Germany, 81675

Klinikum Schwäbisch Gmünd

Mutlangen, Germany, 73557

Kliniken Maria Hilf GmbH; Innere Medizin I; Hämatologie und internistische Onkologie

Mönchengladbach, Germany, 41063

München Klinik Schwabing; Klinik für Hämatologie, Onkologie, Immunologie

München, Germany, 80804

Klinikum der Universität München, Campus Großhadern; Medizinische Klinik und Poliklinik III

München, Germany, 81377

Gemeinschaftspraxis Dr. med. Holger Klaproth

Neunkirchen/Saar, Germany, 66538

Brüderkrankenhaus St. Josef Paderborn

Paderborn, Germany, 33098

Krankenhaus Barmherzige Bruder Regensburg

Regensburg, Germany, 93049

Marienhospital

Stuttgart, Germany, 70199

Robert-Bosch-Krankenhaus

Stuttgart, Germany, 70376

Universitätsklinikum Tübingen

Tübingen, Germany, 72076

Universtitätsklinikum Ulm; Klinik für Innere Medizin III

Ulm, Germany, 89081

Medizinisches Versorgungszentrum Nuklearmedizin-Strahlentherapie-Onkologie

Weiden, Germany, 92367

Italy

Arcispedale S. Anna; Sezione Di Ematologia

Ferrara, Emilia-Romagna, Italy, 44100

Ospedali Riuniti Papardo-Piemonte; Struttura Complessa Di Ematologia

Messina, Lazio, Italy, 98158

Uni Cattolica; Divisione Di Ematologia

Roma, Lazio, Italy, 00168

AOU Città della Salute e della Scienza di Torino - Presidio Le Molinette

Torino, Lazio, Italy, 10126

Ospedale San Raffaele

Milano, Lombardia, Italy, 20132

Az. Osp. S. Maria; Dept. Di Oncologia Medica

Terni, Umbria, Italy, 05100

Ospedale dell' Angelo; U.O. Ematologia

Venezia Mestre, Veneto, Italy, 30174

Mexico

Hospital General de Culiacan

Culiacan, Mexico, 80230

New Zealand

Canterbury Health Laboratories; Haematology

Christchurch, New Zealand, 8011

Dunedin Hospital

Dunedin, New Zealand

Midcentral District Health Board

Palmerston North, New Zealand, 4442

Wellington Hospital

Wellington, New Zealand, 6012

Poland

Uniwersytecki Szpital Kliniczny w Białymstoku, Klinika Hematologii z Pododdziałem Chorob Naczyn

Bialystok, Poland, 15-2

Samodzielny Public Zaklad

Chorzów, Poland, 41-500

Wojewódzki Szpital Specjalistyczny im.MikołajaKopernika;KlinikaHematologiiUniwersytetuMedycznego

Lodz, Poland, 9351

Wojewodzki Szpital Specjalistyczny im. J. Korczaka; Oddział Chorób Wewnetrznych/Hematologiczny

Slupsk, Poland, 76-200

Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wrocławiu; Klinika Hematologii

Wroclaw, Poland, 5036

Romania

Fundeni Clinical Inst. ; Hematology Dept

Bucharest, Romania, 022328

Institutul Regional de Oncologie Iasi; Clinica de Hematologie

Iasi, Romania, 700483

Spitalul Clinic Judetean de Urgenta Targu-Mures; compartiment Hematologie

Targu-mures, Romania, 540136

Russian Federation

Republican Clinical Oncologic Dispensary of Republic Of Tatarstan

Kazan, Russian Federation, 420029

Moscow State Budgetary Healthcare Institution

Moscow, Russian Federation, 123182

Regional Clinical Hospital N.A. Semashko; Hematology

Nizhny Novgorod, Russian Federation, 603126

Penza Regional Oncology Dispensary

Penza, Russian Federation, 440071

Clinical MSCh No1

Perm, Russian Federation, 614077

Rostov State Medical Uni ; Hematology

Rostov-na-donu, Russian Federation, 344022

SBEI of HPE "Bashkir State Medical University" of MoH RF

Ufa, Russian Federation, 450000

Spain

Complejo Hospitalario de Navarra

Pamplona, Navarra, Spain, 31008

Hospital Universitario de Canarias;servicio de Hematologia

La Laguna, Tenerife, Spain, 38320

Hospital del Mar; Servicio de Hematologia

Barcelona, Spain, 08003

Hospital Universitari Vall d'Hebron; Servicio de Hematologia

Barcelona, Spain, 08035

Hospital Clínic i Provincial; Servicio de Hematología y Oncología

Barcelona, Spain, 08036

Hospital Universitario de la Princesa; Servicio de Hematologia

Madrid, Spain, 28006

Hospital Universitario La Paz

Madrid, Spain, 28034

Hospital Universitario Ramón y Cajal

Madrid, Spain, 28034

Hospital Univ. 12 de Octubre; Servicio de Hematologia

Madrid, Spain, 28041

Hospital Clinico Universitario de Salamanca;Servicio de Hematologia

Salamanca, Spain, 37007

Hospital Universitario Virgen del Rocio

Sevilla, Spain, 41013

Complejo Hospitalario de Toledo- H. Virgen de la Salud; Servicio de Hematología

Toledo, Spain, 45004

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Valencia, Spain, 46010

Hospital Arnau de Vilanova (Valencia) Servicio de Hematologia

Valencia, Spain, 46015

Switzerland

Inselspital Bern; Hämatologie und Hämatologisches Zentrallabor

Bern, Switzerland, 3010

Luzerner Kantonsspital, Hämatologie

Luzern, Switzerland, 6000

Universitätsspital Zürich Medizin Hämatologie; Klinik für Hämatologie

Zürich, Switzerland, 8091

United Kingdom

Birmingham Heartlands Hospital

Birmingham, United Kingdom, B9 5SS

Boston Pilgrim Hospital

Boston,Lincolnshire, United Kingdom, PE21 9QS

Western General Hospital; Department of Haematology

Edinburgh, United Kingdom, EH4 2XU

Lincoln County Hospital

Lincoln, United Kingdom, LN2 5QY

University Hospital Southampton NHS Foundation Trust

Southhampton, United Kingdom, SO16 6YD

Sponsors and Collaborators

Hoffmann-La Roche

AbbVie

German CLL Study Group

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

  Study Documents (Full-Text)

Documents provided by Hoffmann-La Roche:

Study Protocol  [PDF] February 12, 2018

Statistical Analysis Plan  [PDF] November 8, 2018

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Samineni D, Gibiansky L, Wang B, Vadhavkar S, Rajwanshi R, Tandon M, Sinha A, Al-Sawaf O, Fischer K, Hallek M, Salem AH, Li C, Miles D. Pharmacokinetics and Exposure-Response Analysis of Venetoclax + Obinutuzumab in Chronic Lymphocytic Leukemia: Phase 1b Study and Phase 3 CLL14 Trial. Adv Ther. 2022 Aug;39(8):3635-3653. doi: 10.1007/s12325-022-02170-w. Epub 2022 Jun 16.

Al-Sawaf O, Zhang C, Lu T, Liao MZ, Panchal A, Robrecht S, Ching T, Tandon M, Fink AM, Tausch E, Schneider C, Ritgen M, Bottcher S, Kreuzer KA, Chyla B, Miles D, Wendtner CM, Eichhorst B, Stilgenbauer S, Jiang Y, Hallek M, Fischer K. Minimal Residual Disease Dynamics after Venetoclax-Obinutuzumab Treatment: Extended Off-Treatment Follow-up From the Randomized CLL14 Study. J Clin Oncol. 2021 Dec 20;39(36):4049-4060. doi: 10.1200/JCO.21.01181. Epub 2021 Oct 28.

Al-Sawaf O, Zhang C, Tandon M, Sinha A, Fink AM, Robrecht S, Samoylova O, Liberati AM, Pinilla-Ibarz J, Opat S, Sivcheva L, Le Du K, Fogliatto LM, Niemann CU, Weinkove R, Robinson S, Kipps TJ, Tausch E, Schary W, Ritgen M, Wendtner CM, Kreuzer KA, Eichhorst B, Stilgenbauer S, Hallek M, Fischer K. Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2020 Sep;21(9):1188-1200. doi: 10.1016/S1470-2045(20)30443-5.

Fischer K, Al-Sawaf O, Bahlo J, Fink AM, Tandon M, Dixon M, Robrecht S, Warburton S, Humphrey K, Samoylova O, Liberati AM, Pinilla-Ibarz J, Opat S, Sivcheva L, Le Du K, Fogliatto LM, Niemann CU, Weinkove R, Robinson S, Kipps TJ, Boettcher S, Tausch E, Humerickhouse R, Eichhorst B, Wendtner CM, Langerak AW, Kreuzer KA, Ritgen M, Goede V, Stilgenbauer S, Mobasher M, Hallek M. Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions. N Engl J Med. 2019 Jun 6;380(23):2225-2236. doi: 10.1056/NEJMoa1815281. Epub 2019 Jun 4.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02242942
• Other Study ID Numbers: BO25323; 2014-001810-24 ( EudraCT Number ); CLL14
• First Posted: September 17, 2014
• Results First Posted: October 1, 2019
• Last Update Posted: December 23, 2022
• Last Verified: December 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Venetoclax; Obinutuzumab; Chlorambucil; Antineoplastic Agents; Antineoplastic Agents, Immunological; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action