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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02242942




Registration number
NCT02242942
Ethics application status
Date submitted
16/09/2014
Date registered
17/09/2014
Date last updated
2/12/2024

Titles & IDs
Public title
Comparison of the Treatments of Obinutuzumab + Venetoclax Versus Obinutuzumab + Chlorambucil in Patients With Chronic Lymphocytic Leukemia
Scientific 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
Secondary ID [1] 0 0
2014-001810-24
Secondary ID [2] 0 0
BO25323
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphocytic Leukemia, Chronic 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Chlorambucil
Treatment: Drugs - Venetoclax
Treatment: Drugs - Obinutuzumab

Experimental: Safety Run-in Obinutuzumab + Venetoclax - Subjects received obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles comprised of 28 days.

Experimental: Obinutuzumab + Chlorambucil - Participants will receive obinutuzumab for 6 cycles and chlorambucil for 12 cycles. Cycles will comprise 28 days.

Experimental: Obinutuzumab + Venetoclax - Participants will receive obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles will comprise 28 days.


Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

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

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/12/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/08/2025
Actual
Sample size
Target
Accrual to date
Final
445
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
Tweed Hospital - Tweed Heads
Recruitment hospital [3] 0 0
The Townsville Hospital - Douglas
Recruitment hospital [4] 0 0
Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology - Woolloongabba
Recruitment hospital [5] 0 0
Royal Adelaide Hospital; Haematology Clinical Trials - Adelaide
Recruitment hospital [6] 0 0
Ashford Cancer Centre Research; Internal Medicine/Medical Oncology - Ashford
Recruitment hospital [7] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [8] 0 0
The Northern Hospital - Epping
Recruitment hospital [9] 0 0
Monash Medical Centre; Haematology - Melbourne
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2485 - Tweed Heads
Recruitment postcode(s) [3] 0 0
4814 - Douglas
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [5] 0 0
5000 - Adelaide
Recruitment postcode(s) [6] 0 0
5035 - Ashford
Recruitment postcode(s) [7] 0 0
3128 - Box Hill
Recruitment postcode(s) [8] 0 0
VIC 3076 - Epping
Recruitment postcode(s) [9] 0 0
3168 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Argentina
State/province [8] 0 0
Buenos Aires
Country [9] 0 0
Austria
State/province [9] 0 0
Innsbruck
Country [10] 0 0
Austria
State/province [10] 0 0
Wien
Country [11] 0 0
Brazil
State/province [11] 0 0
RS
Country [12] 0 0
Brazil
State/province [12] 0 0
SP
Country [13] 0 0
Bulgaria
State/province [13] 0 0
Pleven
Country [14] 0 0
Bulgaria
State/province [14] 0 0
Plovdiv
Country [15] 0 0
Bulgaria
State/province [15] 0 0
Sofia
Country [16] 0 0
Bulgaria
State/province [16] 0 0
Vratsa
Country [17] 0 0
Canada
State/province [17] 0 0
Alberta
Country [18] 0 0
Canada
State/province [18] 0 0
Nova Scotia
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
Croatia
State/province [20] 0 0
Zagreb
Country [21] 0 0
Denmark
State/province [21] 0 0
Herlev
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Denmark
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København Ø
Country [23] 0 0
Denmark
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Roskilde
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Denmark
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Vejle
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Estonia
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Tallinn
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Estonia
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Tartu
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France
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Besançon Cedex
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France
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Caen
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France
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Clermont Ferrand
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France
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Creteil
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France
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Dijon
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France
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Grenoble
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France
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Le Mans
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France
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Lyon
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France
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Montpellier
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France
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Nantes
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France
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Paris
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France
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Rennes
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Rouen
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France
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Toulon
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France
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Villejuif
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Germany
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Aachen
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Germany
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Amberg
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Germany
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Berlin
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Germany
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Dresden
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Germany
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Essen
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Germany
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Esslingen
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Germany
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Frankfurt/Oder
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Germany
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Freiburg
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Germany
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Göttingen
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Germany
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Heidelberg
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Germany
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Herne
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Germany
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Koblenz
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Germany
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Köln
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Germany
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Landshut
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Germany
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Munchen
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Germany
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Mutlangen
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Germany
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Mönchengladbach
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Germany
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München
Country [60] 0 0
Germany
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Neunkirchen/Saar
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Germany
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Paderborn
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Germany
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Regensburg
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Germany
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Stuttgart
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Germany
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Tübingen
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Germany
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Ulm
Country [66] 0 0
Germany
State/province [66] 0 0
Weiden
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Italy
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Emilia-Romagna
Country [68] 0 0
Italy
State/province [68] 0 0
Lazio
Country [69] 0 0
Italy
State/province [69] 0 0
Lombardia
Country [70] 0 0
Italy
State/province [70] 0 0
Umbria
Country [71] 0 0
Italy
State/province [71] 0 0
Veneto
Country [72] 0 0
Mexico
State/province [72] 0 0
Sinaloa
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New Zealand
State/province [73] 0 0
Christchurch
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New Zealand
State/province [74] 0 0
Dunedin
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New Zealand
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Palmerston North
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New Zealand
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Wellington
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Poland
State/province [77] 0 0
Bialystok
Country [78] 0 0
Poland
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Chorzów
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Poland
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Lodz
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Poland
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Slupsk
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Poland
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Wroclaw
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Romania
State/province [82] 0 0
Bucharest
Country [83] 0 0
Romania
State/province [83] 0 0
Iasi
Country [84] 0 0
Romania
State/province [84] 0 0
Targu-mures
Country [85] 0 0
Russian Federation
State/province [85] 0 0
Baskortostan
Country [86] 0 0
Russian Federation
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Moskovskaja Oblast
Country [87] 0 0
Russian Federation
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Niznij Novgorod
Country [88] 0 0
Russian Federation
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Rostov
Country [89] 0 0
Russian Federation
State/province [89] 0 0
Tatarstan
Country [90] 0 0
Russian Federation
State/province [90] 0 0
Penza
Country [91] 0 0
Russian Federation
State/province [91] 0 0
Perm
Country [92] 0 0
Spain
State/province [92] 0 0
Navarra
Country [93] 0 0
Spain
State/province [93] 0 0
Tenerife
Country [94] 0 0
Spain
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Barcelona
Country [95] 0 0
Spain
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Madrid
Country [96] 0 0
Spain
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Salamanca
Country [97] 0 0
Spain
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Sevilla
Country [98] 0 0
Spain
State/province [98] 0 0
Toledo
Country [99] 0 0
Spain
State/province [99] 0 0
Valencia
Country [100] 0 0
Switzerland
State/province [100] 0 0
Bern
Country [101] 0 0
Switzerland
State/province [101] 0 0
Luzern
Country [102] 0 0
Switzerland
State/province [102] 0 0
Zürich
Country [103] 0 0
United Kingdom
State/province [103] 0 0
Birmingham
Country [104] 0 0
United Kingdom
State/province [104] 0 0
Boston,Lincolnshire
Country [105] 0 0
United Kingdom
State/province [105] 0 0
Edinburgh
Country [106] 0 0
United Kingdom
State/province [106] 0 0
Lincoln
Country [107] 0 0
United Kingdom
State/province [107] 0 0
Southhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
AbbVie
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
German CLL Study Group
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT02242942