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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02264574




Registration number
NCT02264574
Ethics application status
Date submitted
1/10/2014
Date registered
15/10/2014

Titles & IDs
Public title
A Multi-Center Study of Ibrutinib in Combination With Obinutuzumab Versus Chlorambucil in Combination With Obinutuzumab in Patients With Treatment naïve Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
Scientific title
A Randomized, Multi-center, Open-label, Phase 3 Study of the Bruton's Tyrosine Kinase Inhibitor Ibrutinib in Combination With Obinutuzumab Versus Chlorambucil in Combination With Obinutuzumab in Subjects With Treatment-naïve Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Secondary ID [1] 0 0
PCYC-1130-CA
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Lymphocytic Leukemia 0 0
Small-Cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
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 - Ibrutinib
Treatment: Drugs - Obinutuzumab
Treatment: Drugs - Chlorambucil

Experimental: IBR + OB - Ibrutinib (IBR) given orally at a dose of 420 mg/day until progressive disease or unacceptable toxicity. Intravenous obinutuzumab (OB) given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until progressive disease or unacceptable toxicity.

Experimental: CLB + OB - Chlorambucil (CLB) given orally at a dose of 0.5 mg/kg body weight up to a total of 6 cycles on Days 1 and 15 of each cycle or until disease progression or unacceptable toxicity.

Intravenous obinutuzumab given on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 1000 mg on Days 8 and 15 of Cycle 1 and 1000 mg on Day 1 of each cycle up to 6 cycles or until disease progression or unacceptable toxicity.


Treatment: Drugs: Ibrutinib
Ibrutinib will be supplied as 140 mg hard gelatin capsules for oral (PO) administration.

Treatment: Drugs: Obinutuzumab
Obinutuzumab will be supplied as 1000 mg/40 mL solution in a single-use vial for intravenous (IV) administration

Treatment: Drugs: Chlorambucil
Chlorambucil will be supplied as 2 mg film-coated tablets for oral (PO) administration

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

Outcomes
Primary outcome [1] 0 0
Primary Analysis: Progression Free Survival (PFS) Based on Independent Review Committee (IRC) Assessment - Kaplan Meier Landmark Estimates at Month 30
Timepoint [1] 0 0
Month 30 (Median follow-up time was 31.3 months at the time of the primary analysis [data cutoff date: 26 March 2018]).
Primary outcome [2] 0 0
Final Analysis: PFS Based on Investigator Assessment - Kaplan Meier Landmark Estimates at Month 48
Timepoint [2] 0 0
Month 48 (Median follow-up time was 44.6 months at the time of the final analysis [data cutoff date: 17 October 2019]).
Secondary outcome [1] 0 0
Primary Analysis: PFS in High-Risk Sub-Population (del17p/TP53 Mutation/Del 11q) Based on IRC Assessment - Kaplan Meier Landmark Estimates at Month 30
Timepoint [1] 0 0
Month 30 (Median follow-up time was 31.3 months at the time of the primary analysis [data cutoff date: 26 March 2018]).
Secondary outcome [2] 0 0
Primary Analysis: Rate of Sustained Hemoglobin Improvement
Timepoint [2] 0 0
Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).
Secondary outcome [3] 0 0
Primary Analysis: Rate of Minimal Residual Disease (MRD)-Negative Response
Timepoint [3] 0 0
Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).
Secondary outcome [4] 0 0
Primary Analysis: Overall Response Rate (ORR) Based on IRC Assessment
Timepoint [4] 0 0
Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).
Secondary outcome [5] 0 0
Primary Analysis: Overall Survival (OS) - Kaplan Meier Landmark Estimates at Month 30
Timepoint [5] 0 0
Month 30 (Median follow-up time was 31.3 months at the time of the primary analysis [data cutoff date: 26 March 2018]).
Secondary outcome [6] 0 0
Primary Analysis: Rate of Grade = 3 or Serious Infusion-Related Reaction (IRR) Adverse Events
Timepoint [6] 0 0
Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).
Secondary outcome [7] 0 0
Primary Analysis: Rate of Sustained Platelet Improvement
Timepoint [7] 0 0
Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).
Secondary outcome [8] 0 0
Primary Analysis: Rate of Clinically Meaningful Improvement in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire EuroQol Five-Dimension (EQ-5D-5L)
Timepoint [8] 0 0
Median follow-up time was 31.3 months at the time of the primary analysis (data cutoff date: 26 March 2018).
Secondary outcome [9] 0 0
Final Analysis: PFS in High-Risk Population (del17p/TP53 Mutation/Del 11q/Unmutated Immunoglobulin Heavy Chain Variable Region [IGHV]) Based on Investigator Assessment - Kaplan Meier Landmark Estimates at Month 48
Timepoint [9] 0 0
Month 48 (Median follow-up time was 44.6 months at the time of the final analysis [data cutoff date: 17 October 2019]).
Secondary outcome [10] 0 0
Final Analysis: Rate of Sustained Hemoglobin Improvement
Timepoint [10] 0 0
Median follow-up time was 44.6 months at the time of the final analysis (data cutoff date: 17 October 2019).
Secondary outcome [11] 0 0
Final Analysis: Rate of Minimal Residual Disease (MRD)-Negative Response
Timepoint [11] 0 0
Median follow-up time was 44.6 months at the time of the final analysis (data cutoff date: 17 October 2019).
Secondary outcome [12] 0 0
Final Analysis: ORR Based on Investigator Assessment
Timepoint [12] 0 0
Median follow-up time was 44.6 months at the time of the final analysis (data cutoff date: 17 October 2019).
Secondary outcome [13] 0 0
Final Analysis: Overall Survival (OS) - Kaplan Meier Landmark Estimates at Month 48
Timepoint [13] 0 0
Month 48 (Median follow-up time was 44.6 months at the time of the final analysis [data cutoff date: 17 October 2019]).
Secondary outcome [14] 0 0
Final Analysis: Rate of Sustained Platelet Improvement
Timepoint [14] 0 0
Median follow-up time was 44.6 months at the time of the final analysis (data cutoff date: 17 October 2019).

Eligibility
Key inclusion criteria
Disease Related:

1. Diagnosis of CLL/SLL that meets IWCLL diagnostic criteria.
2. Age 65 yrs and older OR if less than 65 years, must have at least one of the following criteria:

* Cumulative Illness Rating Score (CIRS) >6
* Creatinine clearance estimated <70 mL/min using Cockcroft-Gault equation.
* Del 17p by fluorescence in situ hybridization (FISH) or TP53 mutation by polymerase chain reaction (PCR) or Next Generation Sequencing
3. Active disease meeting at least 1 of the following IWCLL criteria for requiring treatment:

* Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and thrombocytopenia
* Massive, progressive, or symptomatic splenomegaly
* Massive nodes (at least 10 cm longest diameter), or progressive or symptomatic lymphadenopathy.
* Progressive lymphocytosis with an increase of more than 50 percent over a 2-month period or a lymphocyte doubling time (LDT) of <6 months. LDT may be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In patients with initial blood lymphocyte counts of <30,000/µL, LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (eg, infections) should be excluded.
* Autoimmune hemolytic anemia and/or immune thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy.
* Autoimmune hemolytic anemia is defined by at least one marker of hemolysis (indirect bilirubin above the upper limit of normal (ULN) not due to liver disease, increased lactate dehydrogenase (above ULN) without alternative etiology, or increased absolute reticulocytosis (above ULN) or bone marrow erythropoiesis in the absence of bleeding AND at least one marker direct or indirect autoimmune mechanism (positive direct antiglobulin for immunoglobulin G [IgG] or C3d, cold agglutinins).
* Immune thrombocytopenia is defined by platelets =100,000/µL and increased megakaryocytes on the bone marrow exam.
* Constitutional symptoms, defined as one or more of the following disease-related symptoms or signs, documented in the patient's record prior to randomization:
* unintentional weight loss >10 percent within 6 months prior to screening.
* significant fatigue (inability to work or perform usual activities).
* fevers >100.5°F or 38.0°C for 2 or more weeks prior to screening without evidence of infection.
* night sweats for more than 1 month prior to screening without evidence of infection.
4. Measurable nodal disease by computed tomography (CT), defined as at least 1 lymph node >1.5 cm in the longest diameter in a site that has not been previously irradiated. An irradiated lesion may be assessed for measurable disease only if there has been documented progression in that lesion since radiotherapy has ended.

Laboratory
5. Adequate hematologic function independent of transfusion and growth factor support for at least 7 days prior to screening and randomization.
6. Adequate hepatic and renal function
7. Men and women = 18 years of age.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Any prior treatment of CLL or SLL
2. Evidence of central nervous system (CNS) involvement with primary disease of CLL/SLL
3. History of other malignancies, except:

* Malignancy treated with curative intent and with no known active disease present for =3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician.
4. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura
5. Known or suspected history of Richter's transformation.
6. Concurrent administration of >20mg/day of prednisone within 7 days of randomization unless indicated for prophylaxis or management of allergic reactions (eg, contrast)
7. Known hypersensitivity to one or more study drugs
8. Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
9. Any uncontrolled active systemic infection or an infection requiring systemic treatment that was completed = 7 days before randomization.
10. Known bleeding disorders or hemophilia.
11. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
12. Known history of human immunodeficiency virus (HIV) or active with hepatitis B virus (HBV) or hepatitis C virus (HCV).
13. Major surgery within 4 weeks of randomization.
14. Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk.
15. Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization.
16. Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.
17. Concomitant use of warfarin or other vitamin K antagonists.
18. Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor.
19. Lactating or pregnant
20. Unwilling or unable to participate in all required study evaluations and procedures.
21. Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations).

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
Completed
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)
QLD,SA,VIC
Recruitment hospital [1] 0 0
Site Reference ID/Investigator #0503 - Woolloongabba
Recruitment hospital [2] 0 0
Site Reference ID/Investigator# 0650 - Adelaide
Recruitment hospital [3] 0 0
Site Reference ID/Investigator# 0888 - Ballarat
Recruitment hospital [4] 0 0
Site Reference ID/Investigator# 0193 - Box Hill
Recruitment hospital [5] 0 0
Site Reference ID/Investigator# 0633 - Fitzroy
Recruitment hospital [6] 0 0
Site Reference ID/Investigator# 0170 - Heidelberg
Recruitment postcode(s) [1] 0 0
- Woolloongabba
Recruitment postcode(s) [2] 0 0
- Adelaide
Recruitment postcode(s) [3] 0 0
- Ballarat
Recruitment postcode(s) [4] 0 0
- Box Hill
Recruitment postcode(s) [5] 0 0
- Fitzroy
Recruitment postcode(s) [6] 0 0
- Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Kentucky
Country [4] 0 0
United States of America
State/province [4] 0 0
Nevada
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
Austria
State/province [7] 0 0
Linz
Country [8] 0 0
Austria
State/province [8] 0 0
Salzburg
Country [9] 0 0
Belgium
State/province [9] 0 0
Leuven
Country [10] 0 0
Belgium
State/province [10] 0 0
Turnhout
Country [11] 0 0
Canada
State/province [11] 0 0
Alberta
Country [12] 0 0
Czechia
State/province [12] 0 0
Hradec Kralove
Country [13] 0 0
Czechia
State/province [13] 0 0
Praha 10
Country [14] 0 0
France
State/province [14] 0 0
Gironde
Country [15] 0 0
France
State/province [15] 0 0
Loire Atlantique
Country [16] 0 0
France
State/province [16] 0 0
Meurthe Et Moselle
Country [17] 0 0
France
State/province [17] 0 0
Pyrenees Atlantiques
Country [18] 0 0
Israel
State/province [18] 0 0
Haifa
Country [19] 0 0
Israel
State/province [19] 0 0
Jerusalem
Country [20] 0 0
Israel
State/province [20] 0 0
Petach Tikva
Country [21] 0 0
Israel
State/province [21] 0 0
Tel Aviv
Country [22] 0 0
Israel
State/province [22] 0 0
Zerifin
Country [23] 0 0
Italy
State/province [23] 0 0
Firenze
Country [24] 0 0
Italy
State/province [24] 0 0
Milano
Country [25] 0 0
Italy
State/province [25] 0 0
Modena
Country [26] 0 0
Italy
State/province [26] 0 0
Novara
Country [27] 0 0
Italy
State/province [27] 0 0
Roma
Country [28] 0 0
Italy
State/province [28] 0 0
Siena
Country [29] 0 0
New Zealand
State/province [29] 0 0
Auckland
Country [30] 0 0
New Zealand
State/province [30] 0 0
Hamilton
Country [31] 0 0
Poland
State/province [31] 0 0
Brzozow
Country [32] 0 0
Poland
State/province [32] 0 0
Lodz
Country [33] 0 0
Russian Federation
State/province [33] 0 0
Nizhniy Novgorod
Country [34] 0 0
Russian Federation
State/province [34] 0 0
Ryazan
Country [35] 0 0
Russian Federation
State/province [35] 0 0
Saint-Petersburg
Country [36] 0 0
Russian Federation
State/province [36] 0 0
St. Petersburg
Country [37] 0 0
Russian Federation
State/province [37] 0 0
Yaroslavl
Country [38] 0 0
Spain
State/province [38] 0 0
Madrid
Country [39] 0 0
Spain
State/province [39] 0 0
Barcelona
Country [40] 0 0
Spain
State/province [40] 0 0
Salamanca
Country [41] 0 0
Sweden
State/province [41] 0 0
Borås
Country [42] 0 0
Sweden
State/province [42] 0 0
Luleå
Country [43] 0 0
Sweden
State/province [43] 0 0
Lund
Country [44] 0 0
Sweden
State/province [44] 0 0
Stockholm
Country [45] 0 0
Turkey
State/province [45] 0 0
Nisantasi
Country [46] 0 0
Turkey
State/province [46] 0 0
Ankara
Country [47] 0 0
Turkey
State/province [47] 0 0
Denizli
Country [48] 0 0
Turkey
State/province [48] 0 0
Izmir
Country [49] 0 0
Turkey
State/province [49] 0 0
Samsun
Country [50] 0 0
United Kingdom
State/province [50] 0 0
Essex
Country [51] 0 0
United Kingdom
State/province [51] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pharmacyclics LLC.
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Lori Styles
Address 0 0
Pharmacyclics LLC.
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Requests for access to individual participant data from clinical studies conducted by Pharmacyclics LLC, an AbbVie Company, can be submitted through Yale Open Data Access (YODA) Project site at the following link.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://yoda.yale.edu


What supporting documents are/will be available?

Results publications and other study-related documents

TypeCitations or Other Details
Journal Moreno C, Greil R, Demirkan F, Tedeschi A, Anz B, ... [More Details]