Nilotinib Treatment-free Remission Study in CML (Chronic Myeloid Leukemia) Patients

A Single-arm, Multicenter, Nilotinib Treatment-free Remission Study in Patients With BCR-ABL1 Positive Chronic Myelogenous Leukemia in Chronic Phase Who Have Achieved Durable Minimal Residual Disease (MRD) Status on First Line Nilotinib Treatment.

ClinicalTrials.gov Identifier: NCT01784068

Novartis Reference Number: CAMN107I2201

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

The main purpose of the study is to investigate whether nilotinib treatment can be safely suspended with no recurrence of CML in selected patients who responded optimally on this treatment

Condition 
Chronic Myelogenous Leukemia
Phase 
Phase 2
Overall status 
Active, not recruiting
Enrollment count 
222 participants
Start date 
Mar 04, 2013
Completion date 
Feb 19, 2025
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
Nilotinib followed by treatment-free
Nilotinib will be used as commercial available capsules (except in Japan where clinical supplies is used) of 150 mg and 200 mg strength. treatment occurs during consolidation, continuation, prolonged continuation, re-initiation and re-initiation-2 phases of the study.

Eligibility Criteria

Inclusion Criteria:

Minimum of 2 calendar years of nilotinib treatment with at least the last 12 months of nilotinib treatment prior to pre-screening at approved total dialy dose of 600 mg BID or at a reduced dose of 400 mg QD if required from the perspective of tolerance for BCR-ABL positive CML in documented chronic phase at the time of diagnosis
Evidence of typical BCR-ABL transcripts (b3a2 and/or b2a2) at the time of CML-CP diagnosis i.e. prior to first start of TKI treatment which are amenable to standardized RT-PCR quantification"
Patient in MR4.5 at prescreening at Novartis designated lab
ECOG performance status of 0-2

Adequate end organ function as defined by:

Direct bilirubin ≤ 1.5 x ULN except for i) patients with documented Gilbert's syndrome for whom any bilirubin value is allowed and ii) for patients with asymptomatic hyperbilirubinemia (liver transaminases and alkaline phosphatase within normal range).
SGOT(AST) and SGPT(ALT) ≤ 3 x ULN i.e. equivalent to ≤ Grade 1 NCI-CTCAE v.4.03
Serum lipase ≤ 2 x ULN i.e. equivalent to ≤ Grade 2 NCI-CTCAE v.4.03
Alkaline phosphatase ≤ 2.5 x ULN
Serum creatinine < 1.5 x ULN

Patients must have the following electrolyte values within normal limits or corrected to be within normal limits with supplements prior to first dose of study medication:

Potassium (suggested keep to prevent issues with QT and/or rhythm abnormalities)
Magnesium (suggested keep to prevent issues with QT and/or rhythm abnormalities)
Total calcium (corrected for serum albumin)

Patients must have normal marrow function as defined:

Absolute Neutrophil Count (ANC) ≥ 1.5 x 10E9/L
Hemoglobin ≥ 9.0 g/dL
Platelets ≥ 100 x 10E9/L

Exclusion Criteria:

Previous treatment with BCR-ABL inhibitors other than nilotinib for more than a total cumulative duration of 4 weeks
Previous treatment with alpha-interferon of any duration
Previous anticancer agents for CML other than nilotinib except for cytoreduction after CML diagnosis until up to 4 weeks after first dose of nilotinib
Known second chronic phase of CML after previous progression to AP/BC
Poorly controlled diabetes mellitus (defined as HbA1c > 9%)

Impaired cardiac function including any one of the following:

LVEF < 45% or below the institutional lower limit of the normal range (whichever is higher)
Inability to determine the QT interval on ECG, except for patients with evidence of measurable QT interval at the time of CML diagnosis (e.g. prior to first start of TKI treatment) and who have no documented clinical signs of cardiovascular disease and/or clinical signs of conduction abnormality.
Complete left bundle branch block
Right bundle branch block plus left anterior or posterior hemiblock
Use of a ventricular-paced pacemaker
Congenital long QT syndrome or a known family history of long QT syndrome
History of or presence of clinically significant ventricular or atrial tachyarrhythmias
Clinically significant resting bradycardia
QTc > 450 msec on the average of three serial baseline ECG (using the QTcF formula). If QTcF > 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-tested for QTc.This exclusion criterion is not applicable for patients with non-measurable QT interval who have evidence of measurable QT interval at the time of CML diagnosis (e.g. prior to first start of TKI treatment) and who have no documented clinical signs of cardiovascular disease and/or clinical signs of conduction abnormality.
History or clinical signs of myocardial infarction within 1 year of study entry
History of unstable angina within 1 year of study entry
Other clinically significant heart disease (e.g. congestive heart failure, cardiomyopathy or uncontrolled hypertension)
History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
Known presence of significant congenital or acquired bleeding disorder unrelated to cancer
History of another active malignancy within 5 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively
Treatment with other investigational agents (defined as not used in accordance with the approved indication) within 4 weeks of Day 1
Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. See Appendix 1 for a list of these medications. This list may not be exhaustive.
Patients actively receiving therapy with herbal medicines that are strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. These herbal medicines may include Echinacea, (including E. purpurea, E. angustifolia and E. pallida), Piperine, Artemisinin, St. John's Wort, and Ginkgo.
Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either safely discontinued or switched to a different medication prior to starting study drug. (Please see http://www.torsades.org/medical-pros/drug-lists/printable-drug-list.cfm for a list of agents that prolong the QT interval)
Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery)
Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.

Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during the study and for 14 days after the final dose of nilotinib. Highly effective contraception is defined as either:

Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
Male sterilization (at least 6 months prior to enrolling). For female patients on the study the vasectomized male partner should be the sole partner for that patient.

Use of a combination of any two of the following:

Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception.
Placement of an intrauterine device (IUD) or intrauterine system (IUS)
Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to enrolling. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.

If a study patient becomes pregnant or suspects being pregnant during the study or within 30 days after the final dose of nilotinib, the Study Doctor needs to be informed immediately and ongoing study treatment with nilotinib has to be stopped immediately.

Other protocol-defined inclusion/exclusion criteria may apply.

Study Locations

United States
Florida Cancer Specialists FL Cancer Specialists
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Fort Myers, 33901
Florida
United States
Lakes Research SC
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Miami Lakes, 33014
Florida
United States
H Lee Moffitt Cancer Center and Research Institute SC - 5
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Tampa, 33612
Florida
United States
Cancer Center of Kansas SC
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Wichita, 67214-3728
Kansas
United States
Dana Farber Cancer Institute SC - 8
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Boston, 02215
Massachusetts
United States
Memorial Sloan Kettering SC
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New York, 10017
New York
United States
Oregon Health and Science University SC-6
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Portland, 97239
Oregon
United States
Cancer Centers of the Carolinas Cancer Centers of Carolinas (3
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Greenville, 29605
South Carolina
United States
Sarah Cannon Research Institute Sarah Cannon Research
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Nashville, 37203
Tennessee
United States
Community Cancer Trials of Utah
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Ogden, 84405
Utah
United States
Argentina
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Buenos Aires, C1114AAN
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Argentina
Austria
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Graz, A-8036
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Austria
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Rankweil, A-6830
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Austria
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Salzburg, 5020
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Austria
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Wien, 1140
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Austria
Belgium
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Jette, 1090
Brussel
Belgium
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Sint Niklaas, 9100
Vlaams Brabant
Belgium
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Bruxelles, 1200
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Belgium
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Charleroi, 6000
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Belgium
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Gent, 9000
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Belgium
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Kortrijk, 8500
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Belgium
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Liege, 4000
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Belgium
Bulgaria
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Varna, 9000
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Bulgaria
Colombia
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Bogota, 111411
Cundinamarca
Colombia
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Monteria,
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Colombia
Denmark
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Aarhus, 8000
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Denmark
France
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Bayonne, 64109
Bayonne Cedex
France
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Bordeaux, 33076
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France
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Brest, 29200
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France
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Corbeil Essonnes, 91100
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France
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Dunkerque, 59240
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France
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Grenoble, 38043
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France
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Nantes, 44035
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France
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Rouen Cedex 1, 76038
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France
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Saint Priest en Jarez, 42271
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Strasbourg cedex, 67085
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France
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France
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Germany
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Mannheim, 68305
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Aachen, 52074
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Frankfurt, 60590
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Freiburg, 79106
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Goslar, 38642
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Hamburg, 20246
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Mainz, 55131
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Stuttgart, 70376
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Ulm, 89081
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Athens, 115 27
GR
Greece
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Athens, 106 76
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Greece
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Athens, 115 27
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Greece
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Budapest, 1085
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Hungary
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Budapest, H-1097
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Hungary
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Szeged, H 6725
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Dublin, DUBLIN 8
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Ireland
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Galway,
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Ireland
Italy
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Ancona, 60126
AN
Italy
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Brescia, 25123
BS
Italy
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Cona, 44100
FE
Italy
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Firenze, 50134
FI
Italy
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Genova, 16132
GE
Italy
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Nuoro, 08100
NU
Italy
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Reggio Calabria, 89124
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Italy
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Roma, 00161
RM
Italy
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Orbassano, 10043
TO
Italy
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TR
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Napoli, 80132
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Japan
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Kashiwa-city, 277-8567
Chiba
Japan
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Sapporo city, 060 8648
Hokkaido
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Sagamihara-city, 252-0375
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Kumamoto City, 860-8556
Kumamoto
Japan
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Osaka Sayama, 589 8511
Osaka
Japan
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Suita city, 565 0871
Osaka
Japan
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Saga-city, 849-8501
Saga
Japan
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Kawagoe, 350 8550
Saitama
Japan
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Shimotsuga Gun, 321-0293
Tochigi
Japan
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Bunkyo-ku, 113-8519
Tokyo
Japan
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Shinjuku-ku, 160-0023
Tokyo
Japan
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Akita, 010-8543
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Japan
Netherlands
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Amsterdam, 1081 HV
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Netherlands
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Gdansk, 80-952
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Poland
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Warszawa, 02 106
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Poland
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Oviedo, 33006
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Tarragona, 43005
Catalunya
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Terrassa, 08221
Catalunya
Spain
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Orense, 32005
Galicia
Spain
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Las Palmas de Gran Canaria, 35010
Las Palmas De G.C
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Pamplona, 31008
Navarra
Spain
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La Laguna, 38320
Santa Cruz De Tenerife
Spain
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Baracaldo, 48903
Vizcaya
Spain
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Barcelona, 08041
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Spain
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Madrid, 28006
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Spain
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Madrid, 28034
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Spain
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Madrid, 28040
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Spain
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Madrid, 28041
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Spain
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Madrid, 28046
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Spain
Sweden
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Lund, SE-221 85
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Sweden
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Stockholm, SE-171 76
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Sweden
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Uppsala, SE-751 85
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Sweden
United Kingdom
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Cardiff, CF14 4XW
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United Kingdom
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Oxford, OX3 7LJ
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United Kingdom

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