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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03112174




Registration number
NCT03112174
Ethics application status
Date submitted
4/04/2017
Date registered
13/04/2017
Date last updated
1/07/2024

Titles & IDs
Public title
Study of Ibrutinib Combined With Venetoclax in Subjects With Mantle Cell Lymphoma (SYMPATICO)
Scientific title
Phase 3 Study of Ibrutinib in Combination With Venetoclax in Subjects With Mantle Cell Lymphoma
Secondary ID [1] 0 0
2017-000129-12
Secondary ID [2] 0 0
PCYC-1143-CA
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 - Ibrutinib
Treatment: Drugs - Venetoclax
Treatment: Drugs - Placebo Oral tablet to match Venetoclax

Experimental: Safety Run-in Period - Subjects are enrolled into the open-label Safety Run-in Period to evaluate the occurrence of tumor lysis syndrome (TLS) and DLTs with the concurrent administration of ibrutinib and venetoclax.

Safety run-in phase for the study is closed to further enrollment as of 07-Nov-2018.

Experimental: Phase 3: Ibrutinb + Venetoclax - Subjects will be randomized to receive ibrutinib and venetoclax/placebo until clinical disease progression or unacceptable toxicity

Placebo comparator: Phase 3: Ibrutinib + Placebo - Subjects will be randomized to receive ibrutinib and venetoclax/placebo until clinical disease progression or unacceptable toxicity

Experimental: Treatment-naive - This open-label arm is designed to explore the efficacy and safety of the combination of ibrutinib and venetoclax in subjects with treatment-naive MCL.

Approximately 75 subjects (of which \~25 subjects with TP53 mutation) will be enrolled and treated with ibrutinib and venetoclax.


Treatment: Drugs: Ibrutinib
Administered orally once daily

Treatment: Drugs: Venetoclax
Administered orally once daily

Treatment: Drugs: Placebo Oral tablet to match Venetoclax
Administered orally once daily

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

Outcomes
Primary outcome [1] 0 0
Occurrence of Tumor Lysis Syndrome (TLS) (Safety Run-in Period)
Timepoint [1] 0 0
Approximately 3 months after last subject enrolled into safety run-in portion
Primary outcome [2] 0 0
Occurrence of Dose Limiting Toxicities (DLT) (Safety Run-in Period)
Timepoint [2] 0 0
Approximately 3 months after last subject enrolled into safety run-in portion
Primary outcome [3] 0 0
Number of Participants With Adverse Events (AEs) (Safety Run-in Period)
Timepoint [3] 0 0
Up to approximately 5 years
Primary outcome [4] 0 0
Overall response rate (ORR) (Safety Run-in Period)
Timepoint [4] 0 0
approximately 1 year after last subject has stopped treatment with study drug(s)
Primary outcome [5] 0 0
Duration of Response (DOR) (Safety Run-in Period)
Timepoint [5] 0 0
Up to approximately 5 years
Primary outcome [6] 0 0
Progression-free Survival (PFS) (Safety Run-in Period)
Timepoint [6] 0 0
approximately 1 year after last subject has stopped treatment with study drug(s)
Primary outcome [7] 0 0
Overall Survival (OS) (Safety Run-in Period)
Timepoint [7] 0 0
Up to approximately 5 years
Primary outcome [8] 0 0
Progression-free Survival (PFS) (Randomization Period)
Timepoint [8] 0 0
approximately 1 year after last subject has stopped treatment with study drug(s)
Primary outcome [9] 0 0
Complete Response (CR) (Treatment-Naive Arm)
Timepoint [9] 0 0
approximately 1 year after last subject has stopped treatment with study drug(s)
Secondary outcome [1] 0 0
Complete Response (CR) (Randomization Period)
Timepoint [1] 0 0
approximately 1 year after last subject has stopped treatment with study drug(s)
Secondary outcome [2] 0 0
Overall response rate (ORR) (Randomization Period and Treatment-Naive Arm)
Timepoint [2] 0 0
approximately 1 year after last subject has stopped treatment with study drug(s)
Secondary outcome [3] 0 0
MRD-negative remission rate in participants who achieve CR per investigator assessment (Randomization Period and Treatment-Naive Arm)
Timepoint [3] 0 0
approximately 1 year after last subject has stopped treatment with study drug(s)
Secondary outcome [4] 0 0
Overall Survival (OS) (Randomization Period and Treatment-Naive Arm)
Timepoint [4] 0 0
Up to approximately 5 years
Secondary outcome [5] 0 0
Duration of Response (DOR) (Randomization Period and Treatment-Naive Arm)
Timepoint [5] 0 0
Up to approximately 5 years
Secondary outcome [6] 0 0
Time to Next Treatment (TTNT) (Randomization Period and Treatment-Naive Arm)
Timepoint [6] 0 0
Up to approximately 5 years
Secondary outcome [7] 0 0
Percentage of participants experiencing Adverse Events (Randomization Period)
Timepoint [7] 0 0
Up to approximately 5 years
Secondary outcome [8] 0 0
Occurrence of Tumor Lysis Syndrome (TLS) (Randomization Period)
Timepoint [8] 0 0
Approximately 3 months after last subject enrolled into safety run-in portion
Secondary outcome [9] 0 0
Cmax if Ibrutinib (Randomization Period)
Timepoint [9] 0 0
Week 6
Secondary outcome [10] 0 0
Tmax if Ibrutinib (Randomization Period)
Timepoint [10] 0 0
Week 6
Secondary outcome [11] 0 0
AUClast if Ibrutinib (Randomization Period)
Timepoint [11] 0 0
Week 6
Secondary outcome [12] 0 0
Half-Life (T1/2) if Ibrutinib (Randomization Period)
Timepoint [12] 0 0
Week 6
Secondary outcome [13] 0 0
Cmax of Venetoclax (Randomization Period)
Timepoint [13] 0 0
Week 6
Secondary outcome [14] 0 0
Tmax of Venetoclax (Randomization Period)
Timepoint [14] 0 0
Week 6
Secondary outcome [15] 0 0
AUC of Venetoclax (Randomization Period)
Timepoint [15] 0 0
Week 6
Secondary outcome [16] 0 0
Time to worsening in FACT-Lym subscale of the health-related quality of life (Randomization Period) questionnaire (FACT-Lym)
Timepoint [16] 0 0
Week 6
Secondary outcome [17] 0 0
Duration of CR (Treatment-Naive Arm Period)
Timepoint [17] 0 0
Up to approximately 5 years
Secondary outcome [18] 0 0
Progression-free Survival (PFS) (Treatment-Naive Arm Period)
Timepoint [18] 0 0
approximately 1 year after last subject has stopped treatment with study drug(s)

Eligibility
Key inclusion criteria
Relapsed/Refractory Arm



* Pathologically confirmed MCL (in tumor tissue), with documentation of either overexpression of cyclin D1 in association with other relevant markers (eg, CD19, CD20, PAX5, CD5) or evidence of t(11;14) as assessed by cytogenetics, fluorescent in situ hybridization (FISH), or polymerase chain reaction (PCR).
* At least 1 measurable site of disease on cross-sectional imaging (CT/PET).
* At least 1, but no more than 5, prior treatment regimens for MCL.
* Failure to achieve at least partial response (PR) with, or documented disease progression after, the most recent treatment regimen.
* Subjects must have adequate fresh or paraffin embedded tissue.
* Adequate hematologic, hepatic and renal function.
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of <= 2.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* History or current evidence of central nervous system lymphoma.
* Concurrent enrollment in another therapeutic investigational study or prior therapy with ibrutinib or other BTK inhibitors.
* Prior treatment with venetoclax or other BCL2 inhibitors.
* Anticancer therapy including chemotherapy, radiotherapy, small molecule and investigational agents 21 days prior to receiving the first dose of study drug.
* Treatment with any of the following within 7 days prior to the first dose of study drug: moderate or strong cytochrome P450 3A (CYP3A) inhibitors or strong CYP3A inducers.

Treatment Naïve Arm

Inclusion Criteria:

* Pathologically confirmed treatment-naive MCL (tumor tissue), with documentation of either overexpression of cyclin D1 in association with other relevant markers (eg, CD19, CD20, PAX5, CD5) or evidence of t(11;14), as assessed by cytogenetics, fluorescent in situ hybridization (FISH), or polymerase chain reaction (PCR).
* Men and women =18 years of age with a TP53 mutation.
* At least 1 measurable site of disease.
* Must have adequate fresh or paraffin-embedded tissue.
* Eastern Cooperative Oncology Group (ECOG) performance status score 0-2.
* Adequate hematologic, hepatic, and renal function.



* Blastoid variant of MCL
* History or current evidence of CNS lymphoma.
* Concurrent enrollment in another therapeutic investigational study or prior therapy including ibrutinib or other BTK inhibitors.
* Prior treatment with venetoclax or other BCL2 inhibitors.
* Vaccinated with live, attenuated vaccines within 4 weeks of the first dose of study drug.
* Clinically significant infection requiring IV systemic treatment that was completed <=14 days before the first dose of study drug.
* Any uncontrolled active systemic infection.
* Known bleeding disorders (eg, von Willebrand's disease or hemophilia).
* History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
* History of HIV or active HCV or HBV.
* Major surgery within 4 weeks of the first dose of study drug.
* Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the participant's safety or put the study outcomes at undue risk.
* Currently active, clinically significant cardiovascular disease; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization.
* Unable to swallow capsules or tablets, 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.
* Treatment with any of the following within 7 days prior to the first dose of study drug: Moderate or strong cytochrome P450 3A (CYP3A) inhibitors or moderate or strong CYP3A inducers.
* Known allergy to xanthine oxidase inhibitors and/or rasburicase for subjects with known risk factors (as defined by high tumor burden and/or diminished renal function, as detailed in "Study Design" section above) for TLS.
* Chronic liver disease with hepatic impairment Child-Pugh class B or C.
* Unwilling or unable to participate in all required study evaluations and procedures.
* Known hypersensitivity to the active ingredient or other components of one or more study drugs.

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 assessing the outcomes
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)
ACT,NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
The Canberra Hospital - Canberra
Recruitment hospital [2] 0 0
Border Medical Oncology Research Unit - Albury
Recruitment hospital [3] 0 0
Icon Cancer Care - Auchenflower
Recruitment hospital [4] 0 0
Austin Health - Heidelberg
Recruitment hospital [5] 0 0
Peter MacCallum Cancer - Melbourne
Recruitment hospital [6] 0 0
St.Vincent's Hospital - Melbourne
Recruitment hospital [7] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2605 - Canberra
Recruitment postcode(s) [2] 0 0
2640 - Albury
Recruitment postcode(s) [3] 0 0
4101 - Auchenflower
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
3000 - Melbourne
Recruitment postcode(s) [6] 0 0
3065 - Melbourne
Recruitment postcode(s) [7] 0 0
6009 - Nedlands
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
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Kentucky
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
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
Belgium
State/province [12] 0 0
Antwerpen
Country [13] 0 0
Belgium
State/province [13] 0 0
Brugge
Country [14] 0 0
Belgium
State/province [14] 0 0
Bruxelles
Country [15] 0 0
Belgium
State/province [15] 0 0
Yvoir
Country [16] 0 0
Canada
State/province [16] 0 0
Alberta
Country [17] 0 0
Canada
State/province [17] 0 0
British Columbia
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Canada
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Nova Scotia
Country [19] 0 0
Canada
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Ontario
Country [20] 0 0
Canada
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Quebec
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Czechia
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Brno
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Czechia
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Hradec Králové
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Czechia
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Olomouc
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Czechia
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Ostrava-Poruba
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Czechia
State/province [25] 0 0
Praha 10
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Czechia
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Praha 2
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France
State/province [27] 0 0
Calvados
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France
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Bordeaux
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France
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Clermont Ferrand cedex
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France
State/province [30] 0 0
Marseille
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France
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Nice Cedex 2
Country [32] 0 0
France
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Paris
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France
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Pierre Benite cedex
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France
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Tours Cedex 01
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Germany
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Baden-Wuttemberg
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Germany
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Bayern
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Germany
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Koln
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Germany
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Mainz
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Germany
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Sachsen
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Germany
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Berlin
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Germany
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Essen
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Germany
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Homburg/Saar
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Greece
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Alexandroupolis
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Greece
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Athens
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Greece
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Ioánnina
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Larissa
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Greece
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Patra
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Hungary
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Budapest
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Hungary
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Debrecen
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Hungary
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Gyor
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Hungary
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Kaposvár
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Hungary
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Szeged
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Hungary
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Szombathely
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Italy
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Alessandria/Piemonte
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Italy
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Bergamo/Lombardia
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Italy
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Bologna/Emilia-Romagna
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Italy
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Brescia/Lombardia
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Italy
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Cuneo/Piemonte
Country [59] 0 0
Italy
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Forli-Cesena/Emilia-Rom
Country [60] 0 0
Italy
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Milano/Lombardia
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Italy
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Pavia/Lombardia
Country [62] 0 0
Italy
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Torino/Piemonte
Country [63] 0 0
Italy
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Udine/Friuli-Venezia Giulia
Country [64] 0 0
Korea, Republic of
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Incheon
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Korea, Republic of
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Seoul
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Netherlands
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Groningen
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Netherlands
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Hoofddorp
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Netherlands
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Leiden
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Netherlands
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Rotterdam
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Netherlands
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Schiedam
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Poland
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Bydgoszcz
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Poland
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Chorzów
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Poland
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Kraków
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Warszawa
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Wroclaw
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Poland
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Lódz
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Spain
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Asturias
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Spain
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Barcelona
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Spain
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Navarra
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Spain
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Madrid
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Turkey
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Samsun
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Turkey
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Ankara
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Turkey
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Izmir
Country [84] 0 0
Turkey
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Tekirdag
Country [85] 0 0
Ukraine
State/province [85] 0 0
Cherkasy
Country [86] 0 0
Ukraine
State/province [86] 0 0
Kharkiv
Country [87] 0 0
Ukraine
State/province [87] 0 0
Kyiv
Country [88] 0 0
Ukraine
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Uzhgorod
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Ukraine
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Zhytomyr
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United Kingdom
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Greater London
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United Kingdom
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Greater Manchester
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United Kingdom
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Nottinghamshire
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United Kingdom
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Oxfordshire
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United Kingdom
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Surrey
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United Kingdom
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West Yorkshire
Country [96] 0 0
United Kingdom
State/province [96] 0 0
London

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

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.