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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
5/06/2024

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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
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Croatia
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Zagreb
Country [21] 0 0
Denmark
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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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Caen
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Clermont Ferrand
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Creteil
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France
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Dijon
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Grenoble
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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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Rennes
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Rouen
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Toulon
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France
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Villejuif
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Aachen
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Amberg
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Berlin
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Dresden
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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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Herne
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Koblenz
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Germany
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Köln
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Landshut
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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
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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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Stuttgart
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Germany
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Tübingen
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Germany
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Ulm
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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
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Veneto
Country [72] 0 0
Mexico
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Sinaloa
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New Zealand
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Christchurch
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New Zealand
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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
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Bialystok
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Poland
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Chorzów
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Poland
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Lodz
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Slupsk
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Poland
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Wroclaw
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Romania
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Bucharest
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Romania
State/province [83] 0 0
Iasi
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Romania
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Targu-mures
Country [85] 0 0
Russian Federation
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Baskortostan
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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
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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
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Toledo
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Spain
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Valencia
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Switzerland
State/province [100] 0 0
Bern
Country [101] 0 0
Switzerland
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Luzern
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Switzerland
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Zürich
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United Kingdom
State/province [103] 0 0
Birmingham
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United Kingdom
State/province [104] 0 0
Boston,Lincolnshire
Country [105] 0 0
United Kingdom
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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.