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

Last updated: April 24, 2025
Sponsor: Janssen Research & Development, LLC
Overall Status: Completed

Phase

3

Condition

Lymphoma

Mantle Cell Lymphoma

Lymphoproliferative Disorders

Treatment

Ibrutinib

Bendamustine

Placebo

Clinical Study ID

NCT01776840
CR100967
U1111-1137-0389
PCI-32765MCL3002
2012-004056-11
  • Ages > 65
  • All Genders

Study Summary

The purpose of this study is to evaluate the efficacy and safety of ibrutinib given in combination with bendamustine and rituximab in patients 65 years of age or older with newly diagnosed mantle cell lymphoma.

Eligibility Criteria

Inclusion

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 associationwith 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 polymerasechain reaction (PCR)

  • Clinical Stage II, III, or IV by Ann Arbor Classification

  • At least 1 measurable site of disease according to Revised Response Criteria forMalignant 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

Exclusion

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 withcurative intent and with no known active disease present for >=3 years before randomassignment; adequately treated non-melanoma skin cancer or lentigo maligna withoutevidence of disease; adequately treated cervical carcinoma in situ without evidenceof disease

  • Patients for whom the goal of therapy is tumor debulking prior to stem celltransplant

  • History of stroke or intracranial hemorrhage within 6 months prior to randomassignment

  • Requires anticoagulation with warfarin or equivalent vitamin K antagonists

  • Requires treatment with strong CYP3A inhibitors

  • Clinically significant cardiovascular disease such as uncontrolled or symptomaticarrhythmias, congestive heart failure, or myocardial infarction within 6 months ofScreening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as definedby 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 oractive hepatitis B virus infection or any uncontrolled active systemic infectionrequiring 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 withthe absorption or metabolism of ibrutinib capsules, or put the study outcomes atundue risk

Study Design

Total Participants: 523
Treatment Group(s): 4
Primary Treatment: Ibrutinib
Phase: 3
Study Start date:
May 16, 2013
Estimated Completion Date:
June 24, 2024

Study Description

This is a randomized (individuals assigned to study treatment by chance), double blind (neither physician nor participant knows the treatment that the participant receives), placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial)-controlled study to compare the efficacy and safety of ibrutinib given in combination with bendamustine and rituximab (BR) with BR alone in participants newly diagnosed with mantle cell lymphoma (MCL) who are 65 years of age or older. Approximately 520 participants will be randomly assigned in a 1:1 ratio and stratified by simplified Mantle Cell Lymphoma International Prognostic Index (MIPI) score (low risk [0-3] versus intermediate risk [4-5] versus high risk [6-11]). The treatment phase will extend from randomization until discontinuation of all study treatment or the clinical cutoff for the end of study. A cycle is defined as 28 days. All participants will receive open-label (identity of assigned study drug will be known) BR background therapy for a maximum of 6 cycles; participants with a complete response or partial response will continue to receive open-label background therapy with rituximab maintenance every second cycle for a maximum of 12 additional doses. In addition to the background therapy, all participants will receive blinded study drug (ibrutinib or placebo). Participants randomized to treatment Arm A will receive placebo capsules and participants randomized to treatment Arm B will receive ibrutinib capsules. Study drug will be administered daily and continuously until disease progression, unacceptable toxicity, or study end. Participants with stable disease after initial chemoimmunotherapy (BR+ibrutinib/placebo) should continue treatment with ibrutinib/placebo until disease progression, unacceptable toxicity, or study end. Participants with progressive disease must discontinue all study treatment. For participants who discontinue background therapy and do not have progressive disease, treatment with study drug will continue until disease progression or unacceptable toxicity or the clinical cutoff for the final analysis of progression-free survival (PFS). Participants receiving BR, rituximab, or ibrutinib at the clinical cutoff for the final analysis of PFS will continue open-label treatment until disease progression or unacceptable toxicity. Placebo will be stopped when the study is unblinded for the clinical cutoff for the final analysis of PFS. The posttreatment follow-up phase will begin once a participant discontinues bendamustine and rituximab and study drug. Participants who discontinue for reasons other than disease progression must continue to have disease evaluations as outlined in the protocol. Participants who discontinue due to disease progression will be followed for survival and subsequent anti-MCL therapy. The posttreatment follow-up phase will continue until death, lost to follow up, consent withdrawal, or study end, whichever occurs first. Four clinical cutoffs are planned. The first 3 clinical cutoffs will occur when approximately 134, 180, and 265 PFS events have been observed, respectively. The interim analyses and the final analysis of PFS will take place at these 3 clinical cutoffs, respectively; participant treatment assignment will be unblinded and placebo treatment will be stopped at the clinical cutoff for the final analysis of PFS. Treatment unblinding and stopping of placebo treatment could occur before the planned final analysis of PFS if recommended by the independent Data Monitoring Committee (DMC) after an interim analysis. The last cutoff will occur at the end of study, when 60% of the randomized participants have died or the Sponsor terminates the study, whichever comes first. Efficacy assessments will be conducted in accordance with the Revised Response Criteria for Malignant Lymphoma. Safety will be monitored throughout the study and summarized. Blood samples will be drawn for assessment of pharmacokinetic parameters. Blood and bone marrow will be collected for assessment of minimal residual disease and biomarker studies.

Connect with a study center

  • Buenos Aires,
    Argentina

    Site Not Available

  • Ciudad Autonoma de Buenos Aires,
    Argentina

    Site Not Available

  • Cordoba,
    Argentina

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    Córdoba,
    Argentina

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    Federal,
    Argentina

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  • La Capital,
    Argentina

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    La Plata,
    Argentina

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  • Parana,
    Argentina

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  • Adelaide,
    Australia

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  • Auchenflower,
    Australia

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  • Box Hill,
    Australia

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  • Concord,
    Australia

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  • Douglas,
    Australia

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  • Gosford,
    Australia

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  • Hobart,
    Australia

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    Hobart, Tasmania,
    Australia

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    Melbourne,
    Australia

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  • Prahran,
    Australia

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    South Brisbane,
    Australia

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    Westmead,
    Australia

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  • Antwerpen,
    Belgium

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  • Brugge,
    Belgium

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  • Brussels,
    Belgium

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    Edegem,
    Belgium

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  • Gent,
    Belgium

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  • Leuven,
    Belgium

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    Liege,
    Belgium

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  • Wilrijk,
    Belgium

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  • Yvoir,
    Belgium

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  • Barretos,
    Brazil

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    Florianopolis,
    Brazil

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    Brazil

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    Goiânia,
    Brazil

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    Brazil

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    Juiz De Fora,
    Brazil

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    Brazil

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  • Ribeirao Preto,
    Brazil

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    Ribeirão Preto,
    Brazil

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  • Rio de Janeiro,
    Brazil

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    Brazil

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    São Paulo,
    Brazil

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    Brazil

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    São Paulol,
    Brazil

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  • Edmonton, Alberta
    Canada

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  • Vancouver, British Columbia
    Canada

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  • Hamilton, Ontario
    Canada

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  • Ottawa, Ontario
    Canada

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  • Montreal, Quebec
    Canada

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    Santiago,
    Chile

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    Temuco,
    Chile

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    Vina Del Mar,
    Chile

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  • Beijing,
    China

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    China

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    China

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    China

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    China

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    China

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    Bogota,
    Colombia

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    Cali,
    Colombia

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    Medellin N/A,
    Colombia

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    Praha 2,
    Czech Republic

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  • Brno,
    Czechia

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  • Hradec Kralove,
    Czechia

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  • Praha 10,
    Czechia

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  • Creteil,
    France

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  • F-75 730 Paris Cedex 15,
    France

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  • Grenoble,
    France

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  • Nantes,
    France

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  • Paris,
    France

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    France

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    Germany

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    Essen,
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    Köln,
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    Germany

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    Germany

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    Germany

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    Germany

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    Villingen,
    Germany

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    Germany

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    Würzburg,
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  • Athens,
    Greece

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    Greece

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    Greece

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    Hong Kong,
    Hong Kong

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  • Budapest N/a,
    Hungary

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    Hungary

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    Hungary

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  • Pecs,
    Hungary

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    Pécs N/A,
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    Hungary

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    Szeged N/A,
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    Szolnok,
    Hungary

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  • Dublin,
    Ireland

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    Ireland

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    Galway N/A,
    Ireland

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  • Afula,
    Israel

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    Israel

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  • Jerusalem,
    Israel

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    Israel

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    Israel

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    Israel

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  • Tel Aviv,
    Israel

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    Israel

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  • Fukuoka,
    Japan

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    Japan

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    Isehara,
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    Kumamoto,
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    Sendai,
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  • Gyeonggi-do,
    Korea, Republic of

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    Hwasun Gun,
    Korea, Republic of

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    Guadalajara,
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    Mexico,
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    Mexico

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    Queretaro,
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    Zapopan,
    Mexico

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  • Amsterdam Zuidoost,
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    Den Haag,
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  • Groningen,
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    Nieuwegein,
    Netherlands

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    Netherlands

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    Lima,
    Peru

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  • Bydgoszcz,
    Poland

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    Poland

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    Poland

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  • Warszawa,
    Poland

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    Poland

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    Zamosc,
    Poland

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    Braga,
    Portugal

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    Coimbra,
    Portugal

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    Porto,
    Portugal

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    Vila Nova De Gaia,
    Portugal

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  • San Juan,
    Puerto Rico

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    Arkhangelsk,
    Russian Federation

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  • Chelyabinsk,
    Russian Federation

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  • Ekaterinburg,
    Russian Federation

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    Izhevsk,
    Russian Federation

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    Kazan,
    Russian Federation

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    Kirov,
    Russian Federation

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  • Krasnodar,
    Russian Federation

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  • Moscow,
    Russian Federation

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  • Moscow N/a,
    Russian Federation

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  • Nizhny Novgorod,
    Russian Federation

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  • Novosibirsk,
    Russian Federation

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    Obninsk,
    Russian Federation

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    Perm,
    Russian Federation

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  • Petrozavodsk,
    Russian Federation

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  • Rostov-Na-Donu,
    Russian Federation

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  • Ryazan,
    Russian Federation

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    Saint Petersburg,
    Russian Federation

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    Saint-Petersburg,
    Russian Federation

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  • Sochi,
    Russian Federation

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    St,
    Russian Federation

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  • St-Petersburg,
    Russian Federation

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    St.-Petersburg,
    Russian Federation

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    Russian Federation

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  • Syktyvkar,
    Russian Federation

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  • Volgograd,
    Russian Federation

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    Singapore,
    Singapore

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  • Banska Bystrica,
    Slovakia

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  • Bratislava,
    Slovakia

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  • Kosice,
    Slovakia

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  • Martin,
    Slovakia

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  • Presov 1,
    Slovakia

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  • Barcelona,
    Spain

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  • Madrid,
    Spain

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  • Oviedo,
    Spain

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  • Palma De Mallorca,
    Spain

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  • Salamanca,
    Spain

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  • Santiago De Compostela,
    Spain

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  • Linköping,
    Sweden

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  • Lund,
    Sweden

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  • Stockholm,
    Sweden

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  • Umeaa,
    Sweden

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  • Uppsala,
    Sweden

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  • Changhua,
    Taiwan

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  • Kaohsiung County,
    Taiwan

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  • Taichung,
    Taiwan

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    Taichung City,
    Taiwan

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  • Tainan,
    Taiwan

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  • Taipei,
    Taiwan

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  • Taoyuan,
    Taiwan

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  • Adana,
    Turkey

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  • Ankara,
    Turkey

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  • Diyarbakir,
    Turkey

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  • Istanbul,
    Turkey

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  • Izmir,
    Turkey

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  • Kayseri,
    Turkey

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  • Mersin,
    Turkey

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  • Cherkassy,
    Ukraine

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    Dnepropetrovsk,
    Ukraine

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  • Donetsk,
    Ukraine

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  • Khmelnitskiy,
    Ukraine

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  • Kiev,
    Ukraine

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  • Lviv,
    Ukraine

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    Simferopol,
    Ukraine

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  • Canterbury,
    United Kingdom

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  • Glasgow,
    United Kingdom

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  • Leeds,
    United Kingdom

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  • Leicester,
    United Kingdom

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  • Liverpool,
    United Kingdom

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  • London,
    United Kingdom

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  • Manchester,
    United Kingdom

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  • Plymouth,
    United Kingdom

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  • Southampton,
    United Kingdom

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  • Sutton,
    United Kingdom

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    Truro,
    United Kingdom

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  • Tucson, Arizona
    United States

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    Berkeley, California
    United States

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  • Burbank, California
    United States

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  • La Jolla, California
    United States

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    Santa Monica, California
    United States

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  • Stanford, California
    United States

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    Aurora, Colorado
    United States

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  • Denver, Colorado
    United States

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  • New Haven, Connecticut
    United States

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  • Stamford, Connecticut
    United States

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  • empty

    Tampa, Florida
    United States

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  • empty

    West Palm Beach, Florida
    United States

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  • empty

    Atlanta, Georgia
    United States

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  • Chicago, Illinois
    United States

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  • Maywood, Illinois
    United States

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  • Niles, Illinois
    United States

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  • Springfield, Illinois
    United States

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  • empty

    Urbana, Illinois
    United States

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  • Goshen, Indiana
    United States

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  • empty

    Indianapolis, Indiana
    United States

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  • empty

    Vincennes, Indiana
    United States

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  • Iowa City, Iowa
    United States

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  • Sioux City, Iowa
    United States

    Site Not Available

  • Topeka, Kansas
    United States

    Site Not Available

  • Westwood, Kansas
    United States

    Site Not Available

  • Lexington, Kentucky
    United States

    Site Not Available

  • Louisville, Kentucky
    United States

    Site Not Available

  • empty

    Paducah, Kentucky
    United States

    Site Not Available

  • Metairie, Louisiana
    United States

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  • Ann Arbor, Michigan
    United States

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  • Detroit, Michigan
    United States

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  • empty

    Woodbury, Minnesota
    United States

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  • empty

    Hattiesburg, Mississippi
    United States

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  • Jefferson City, Missouri
    United States

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  • Lincoln, Nebraska
    United States

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  • empty

    Henderson, Nevada
    United States

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  • Hackensack, New Jersey
    United States

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  • empty

    Morristown, New Jersey
    United States

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  • New Brunswick, New Jersey
    United States

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  • Albuquerque, New Mexico
    United States

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  • Albany, New York
    United States

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  • Hawthorne, New York
    United States

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  • empty

    New Hyde Park, New York
    United States

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  • New York, New York
    United States

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  • empty

    Valhalla, New York
    United States

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  • Durham, North Carolina
    United States

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  • Bismarck, North Dakota
    United States

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  • Fargo, North Dakota
    United States

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  • Eugene, Oregon
    United States

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  • Portland, Oregon
    United States

    Site Not Available

  • Philadelphia, Pennsylvania
    United States

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    Pittsburgh, Pennsylvania
    United States

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  • Greenville, South Carolina
    United States

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    Sioux Falls, South Dakota
    United States

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  • Watertown, South Dakota
    United States

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  • Nashville, Tennessee
    United States

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  • Houston, Texas
    United States

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  • San Antonio, Texas
    United States

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  • Burlington, Vermont
    United States

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  • Spokane, Washington
    United States

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  • Vancouver, Washington
    United States

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    Morgantown, West Virginia
    United States

    Site Not Available

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