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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01776840




Registration number
NCT01776840
Ethics application status
Date submitted
24/01/2013
Date registered
28/01/2013
Date last updated
28/08/2024

Titles & IDs
Public title
A Study of the Bruton's Tyrosine Kinase Inhibitor Ibrutinib Given in Combination With Bendamustine and Rituximab in Patients With Newly Diagnosed Mantle Cell Lymphoma
Scientific title
A Randomized, Double-blind, Placebo-controlled Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, PCI-32765 (Ibrutinib), in Combination With Bendamustine and Rituximab (BR) in Subjects With Newly Diagnosed Mantle Cell Lymphoma
Secondary ID [1] 0 0
PCI-32765MCL3002
Secondary ID [2] 0 0
CR100967
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mantle 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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Bendamustine
Treatment: Drugs - Rituximab
Treatment: Drugs - Ibrutinib
Treatment: Drugs - Placebo

Placebo comparator: Treatment Arm A -

Experimental: Treatment Arm B -


Treatment: Drugs: Bendamustine
90 mg/m2 administered intravenously on Days 1-2, Cycles 1-6

Treatment: Drugs: Rituximab
375 mg/m2 administered intravenously on Day 1, Cycles 1-6; if complete response or partial response is achieved, 375 mg/m2 is administered on Day 1 of every second cycle for a maximum of 12 additional doses

Treatment: Drugs: Ibrutinib
560 mg (4 x 140 mg capsules) administered orally once daily continuously starting on Day 1, Cycle 1 until disease progression, or unacceptable toxicity, or study end

Treatment: Drugs: Placebo
4 capsules administered orally once daily continuously starting on Day 1, Cycle 1 until disease progression, or unacceptable toxicity, or the final analysis of progression-free survival

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

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS)
Timepoint [1] 0 0
Up to 97 months
Secondary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
Up to 97 months
Secondary outcome [2] 0 0
Complete Response Rate
Timepoint [2] 0 0
Up to 97 months
Secondary outcome [3] 0 0
Time-to-Next Treatment
Timepoint [3] 0 0
Up to 97 months
Secondary outcome [4] 0 0
Percentage of Participants With Overall Response
Timepoint [4] 0 0
Up to 97 months
Secondary outcome [5] 0 0
Minimal Residual Disease (MRD)-Negative Response Rate
Timepoint [5] 0 0
Up to 97 months
Secondary outcome [6] 0 0
Time to Worsening (TTW) in the Lymphoma (Lym) Subscale of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Questionnaire
Timepoint [6] 0 0
Up to 97 months
Secondary outcome [7] 0 0
Duration of Response (DoR)
Timepoint [7] 0 0
Up to 97 months
Secondary outcome [8] 0 0
Duration of Complete Response (DoCR)
Timepoint [8] 0 0
Up to 97 months
Secondary outcome [9] 0 0
Time to Response
Timepoint [9] 0 0
Up to 97 months
Secondary outcome [10] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Timepoint [10] 0 0
Up to 97 months
Secondary outcome [11] 0 0
Oral Plasma Clearance (CL/F) of Ibrutinib
Timepoint [11] 0 0
Day 2 of Cycles 1, 2 and 3 (each cycle was of 28 days)
Secondary outcome [12] 0 0
Oral Volume of Distribution at Steady State of Ibrutinib
Timepoint [12] 0 0
Day 2 of Cycles 1, 2 and 3 (each cycle was of 28 days)
Secondary outcome [13] 0 0
Area Under the Concentration Curve of Ibrutinib During 24 Hours After Dosing at Steady State
Timepoint [13] 0 0
Day 2 of Cycles 1, 2 and 3 (each cycle was of 28 days)
Secondary outcome [14] 0 0
Minimum Observed Plasma Concentration of Ibrutinib
Timepoint [14] 0 0
Day 2 of Cycles 1, 2 and 3 (each cycle was of 28 days)
Secondary outcome [15] 0 0
Maximum Observed Plasma Concentration of Ibrutinib
Timepoint [15] 0 0
Day 2 of Cycles 1, 2 and 3 (each cycle was of 28 days)

Eligibility
Key inclusion criteria
* Diagnosis of mantle cell lymphoma (MCL) reviewed and approved by central laboratory: diagnosis must include morphology and expression of either cyclin D1 in association with other relevant markers (eg, CD19, CD20, PAX5 and CD5) or evidence of t(11;14) as assessed by cytogenetics, fluorescent in situ hybridization (FISH), or polymerase chain reaction (PCR)
* Clinical Stage II, III, or IV by Ann Arbor Classification
* At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma
* No prior therapies for MCL
* Eastern Cooperative Oncology Group (ECOG) performance status grade 0 or 1
* Hematology and biochemical laboratory values within protocol-defined limits
* Agrees to protocol-defined use of effective contraception
* Negative blood or urine pregnancy test at screening
Minimum age
65 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Major surgery within 4 weeks of random assignment
* Known central nervous system lymphoma
* Diagnosed or treated for malignancy other than MCL, except: malignancy treated with curative intent and with no known active disease present for >=3 years before random assignment; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated cervical carcinoma in situ without evidence of disease
* Patients for whom the goal of therapy is tumor debulking prior to stem cell transplant
* History of stroke or intracranial hemorrhage within 6 months prior to random assignment
* Requires anticoagulation with warfarin or equivalent vitamin K antagonists
* Requires treatment with strong CYP3A inhibitors
* Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
* Vaccinated with live, attenuated vaccines within 4 weeks of random assignment
* Known history of human immunodeficiency virus (HIV) or active hepatitis C virus or active hepatitis B virus infection or any uncontrolled active systemic infection requiring intravenous antibiotics
* Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
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)
Recruitment hospital [1] 0 0
- Adelaide
Recruitment hospital [2] 0 0
- Auchenflower
Recruitment hospital [3] 0 0
- Box Hill
Recruitment hospital [4] 0 0
- Concord
Recruitment hospital [5] 0 0
- Douglas
Recruitment hospital [6] 0 0
- Gosford
Recruitment hospital [7] 0 0
- Hobart
Recruitment hospital [8] 0 0
- Prahran
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Auchenflower
Recruitment postcode(s) [3] 0 0
- Box Hill
Recruitment postcode(s) [4] 0 0
- Concord
Recruitment postcode(s) [5] 0 0
- Douglas
Recruitment postcode(s) [6] 0 0
- Gosford
Recruitment postcode(s) [7] 0 0
- Hobart
Recruitment postcode(s) [8] 0 0
- Prahran
Recruitment outside Australia
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United States of America
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Arizona
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California
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Colorado
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Connecticut
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Illinois
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Indiana
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Iowa
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Kansas
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Kentucky
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Michigan
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Missouri
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Nebraska
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New Mexico
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North Carolina
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Tennessee
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Vermont
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Washington
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Argentina
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Buenos Aires
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Argentina
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Ciudad Autonoma de Buenos Aires
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Argentina
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Cordoba
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Argentina
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La Capital
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Argentina
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Parana
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Belgium
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Antwerpen
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Brugge
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Gent
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Leuven
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Yvoir
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Alberta
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Ontario
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Tianjin
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Brno
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Hradec Kralove
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Praha 10
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Creteil
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F-75 730 Paris Cedex 15
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Pessac
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Tours Cedex 9
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Berlin
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Heidelberg
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Jena
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Mainz
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Germany
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München
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TÿBINGEN
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Ulm
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Germany
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Villingen-Schwenningen
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Athens Attica
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Athens
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Greece
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Thessalonikis
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Hungary
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Budapest N/a
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Hungary
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Debrecen
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Kaposvár
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Afula
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Haifa
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Nahariya
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Petach Tikva
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Ramat-Gan
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Fukuoka
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Kyoto
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Japan
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Nagoya
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Japan
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Osaka
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Japan
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Sapporo
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Sendai-shi
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Japan
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Suita
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Tokyo
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Korea, Republic of
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Gyeonggi-do
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Korea, Republic of
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Jeollanam-do
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Seoul
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Monterrey
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Mexico
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Oaxaca
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Netherlands
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Amsterdam Zuidoost
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Dordrecht
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Groningen
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Leiden
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Rotterdam
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Netherlands
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Utrecht
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Poland
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Bydgoszcz
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Krakow
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Olsztyn
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Russian Federation
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Russian Federation
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Ekaterinburg
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Russian Federation
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Krasnodar
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Russian Federation
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Moscow N/a
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Russian Federation
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Moscow
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Russian Federation
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Nizhny Novgorod
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Russian Federation
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Novosibirsk
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Russian Federation
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Petrozavodsk
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Russian Federation
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Rostov-Na-Donu
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Russian Federation
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Ryazan
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Russian Federation
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Sochi
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Russian Federation
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St-Petersburg
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Russian Federation
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St.Petersurg
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Russian Federation
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Syktyvkar
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Russian Federation
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Volgograd
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Slovakia
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Banska Bystrica
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Slovakia
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Bratislava
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Slovakia
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Kosice
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Slovakia
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Martin
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Slovakia
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Presov 1
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Oviedo
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Spain
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Palma De Mallorca
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Spain
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Salamanca
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Spain
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Santiago De Compostela
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Sweden
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Linköping
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Sweden
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Lund
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Sweden
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Stockholm
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Sweden
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Umeaa
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Uppsala
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Taichung
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Tainan
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Taipei
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Taoyuan
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Turkey
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Istanbul
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Mersin
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Ukraine
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Cherkassy
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Ukraine
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Donetsk
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Ukraine
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Khmelnitskiy
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Ukraine
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Kiev
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Ukraine
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Lviv
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United Kingdom
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Canterbury
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Glasgow
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Leeds
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United Kingdom
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Leicester
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Liverpool
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London
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Manchester
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Plymouth
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United Kingdom
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Southampton
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United Kingdom
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Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Janssen Research & Development, LLC
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Pharmacyclics LLC.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, 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

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.