Efficacy and Safety Study of Lenalidomide Plus R-CHOP Chemotherapy Versus Placebo Plus R-CHOP Chemotherapy in Untreated ABC Type Diffuse Large B-cell Lymphoma
- Conditions
- Lymphoma, Large B-Cell, Diffuse
- Interventions
- Registration Number
- NCT02285062
- Lead Sponsor
- Celgene
- Brief Summary
To evaluate the efficacy and safety of lenalidomide, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R2-CHOP) chemotherapy versus placebo, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (placebo-R-CHOP) chemotherapy in patients who have previously untreated ABC type DLBCL.
- Detailed Description
This research study is for patients with newly diagnosed Diffuse Large B-cell Lymphoma (DLBCL) of the activated B-cell (ABC) type who have not yet been treated. DLBCL is a cancer of a type of blood cell called B-lymphocytes. B lymphocytes are part of the body's immune system. There are different types of DLBCL. About a third of newly diagnosed DLBCL cancers are the ABC type. It has been observed that treatment does not work as well for patients with the ABC type compared to patients with other DLBCL types who receive standard treatment. However, at this time both ABC type and other DLBCL type patients receive the same standard treatments.
Patients with DLBCL who are otherwise healthy are usually treated first with the chemotherapy drug combination called R-CHOP. The drugs in this combination are "R" for rituximab, "C" for cyclophosphamide, "H" for doxorubicin which has a chemical name of hydroxydaunomycin, "O" for vincristine which has a trade name of oncovin, and "P" for prednisone. Depending on the local practice where you are treated, R-CHOP may be given for 6 or 8 cycles. A cycle could lasts for 14 or 21 days. The R-CHOP drug combination is approved for the treatment of DLBCL of all types, including ABC type. R-CHOP is standard care.
This study will test the standard R-CHOP21 against R-CHOP21 plus lenalidomide. The purpose is to see whether adding lenalidomide works better and is as safe as R-CHOP by itself. This study is only for patients with ABC type DLBCL who have not yet been treated. Lenalidomide is not approved for use in DLBCL. Its use in this disease is experimental. In this study, the experimental treatment is lenalidomide + R-CHOP21 x 6.
This study will use a gene expression profile (GEP) test to see if a patient has the ABC type. The results of this GEP test affect whether you may be treated on this study. Because the performance of this test has not been proven, it is for investigational use only, and is still under development. This means the GEP test is an experimental test.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 570
- Histologically proven Diffuse Large B-Cell Lymphoma of the Activated B-Cell type
- Newly diagnosed, previously untreated Diffuse Large B-Cell Lymphoma
- Measurable Diffuse Large B-Cell Lymphoma disease by Computed Tomography (CT) / Magnetic Resonance Imagining (MRI) scans
- Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
- Age 18 - 80 years; age > 80 allowed at investigator discretion if performance status ≤ 1; and each organ system score ≤ 2 using cumulative illness rating scale (CIRS)
- Diagnosis of lymphoma histologies other than Diffuse Large B-Cell Lymphoma
- History of malignancies, other than Diffuse Large B-Cell Lymphoma, unless the patient has been disease free for 5 years or more
- Known seropositive for, or history of, active Human Immunodeficiency Virus (HIV) Hepatitis B Virus (HBV), Hepatitis C Virus (HCV)
- Contraindication to any drug in the chemotherapy regimen, and specifically: LVEF (Left Ventricular Ejection Fraction) < 45% or peripheral neuropathy grade 2
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description R2-CHOP Rituximab Lenalidomide plus R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) R2-CHOP Cyclophosphamide Lenalidomide plus R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) R-CHOP Placebo Placebo plus R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) R2-CHOP lenalidomide Lenalidomide plus R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) R-CHOP Rituximab Placebo plus R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) R-CHOP vincristine Placebo plus R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) R2-CHOP prednisone Lenalidomide plus R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) R-CHOP Cyclophosphamide Placebo plus R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) R2-CHOP Doxorubicin Lenalidomide plus R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) R2-CHOP vincristine Lenalidomide plus R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) R-CHOP prednisone Placebo plus R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) R-CHOP Doxorubicin Placebo plus R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)
- Primary Outcome Measures
Name Time Method Kaplan-Meier Estimate of Progression Free Survival (PFS) From the date of randomization up to the data cut off date of 15 March 2019; median follow-up of 24.5 months Progression free survival was defined as the time (months) from the date of randomization to the date of disease progression or death (any cause), whichever occurred earlier and was assessed by the Independent Response Adjudication Committee (IRAC). Relapse from complete response (CR) was considered as disease progression throughout the study. Disease progression was determined based on the Revised Response Criteria for Malignant Lymphoma. The PFS analysis was based on the censoring rules using the Food and Drug Administration (FDA) Guidance. Participants who did not experience disease progression and who did not die before the clinical data cutoff date were censored at the date of last adequate response assessment.
- Secondary Outcome Measures
Name Time Method Kaplan-Meier (K-M) Estimate of Event Free Survival (EFS) From the date of randomization up to the data cut off date of 15 March 2019; median follow-up was 24.5 months EFS was defined as the time (months) from randomization until occurrence of one of the following events, whichever occurred first: • Disease progression • Initiation of subsequent systemic anti-lymphoma therapy • Death due to any cause The assessment of EFS was conducted by the IRAC using the International Working Group (IWG) criteria for NHL. Pre-specified optional therapies such as the extra 2 doses of single agent rituximab after Cycle 6 or consolidation radiotherapy did not count as an EFS event (initiation of subsequent systemic anti-lymphoma therapy) if the decision to treat and the location to be treated was determined prior to randomization. Participants who did not experience any of the events defined in the categories above before the clinical data cutoff date were censored at date last known alive.
K-M Estimate of Overall Survival (OS) From randomization until death due to any cause (up to approximately 86 months) Overall survival was assessed by the Independent Response Adjudication Committee (IRAC) and defined as time from randomization until death due to any cause. Participants who withdrew consent were censored at the time of withdrawal. Participants who were still alive before the clinical data cutoff date and participants who were lost to follow-up were censored at date last known alive.
Percentage of Participants Who Completed the Euroqol 5-Dimension 3-Level (EQ-5D-3L) Health Related Quality of Life (HR-QoL) Questionnaire Screening, Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34 The completion rate for EQ-5D assessments was judged by looking at the number of completed assessments at each time point. Completion rates were calculated as the number and percentage of participants out of the total number of patients in the ITT population and summarized by visit/cycle and treatment group. The EQ-5D-3L is a generic, self-reported preference-based measure of health across five dimensions: mobility, self-care, pain, usual activities, and anxiety/depression. Each dimension has three levels of 'severity' corresponding to "no problems", "some problems" and "extreme problems". The instrument is scored using the United Kingdom (UK) index ranges from -0.594 - 1, where 0 equates to death and 1 equates to full health -0.594 is considered 'worse than death'.
Percentage of Participants Who Achieved a Complete Response (CR) From randomization date up to the data cut off date of 15 March 2019; median follow-up was 24.5 months The percentage of participants who achieved a CR after initiation of the study treatment and prior to initiation of subsequent systemic antilymphoma therapy as assessed by the IRAC. A CR = complete metabolic response; target nodes/nodal masses regressed on computed tomography to (≤ 1.5 cm in their greatest transverse diameter for nodes \> 1.5 cm prior to therapy. Regressed to normal size by imaging, and absence of nodules related to lymphoma. If bone marrow was involved prior to therapy, no evidence of fluorodeoxyglucose avid disease in marrow per International Working Group (IWG) 2014 for Non-Hodgkin's Lymphoma (NHL). Participants who did not have any adequate response assessments during this period were not considered as responders.
Percentage of Participants Who Achieved an Objective Response From randomization date up to the data cut off date of 15 March 2019; median total treatment duration was 18.10 weeks for both treatment arms; range = 1.6 to 29.0 weeks for R2-CHOP arm and 0.3 to 22.9 weeks for placebo-R-CHOP arm An objective response = percentage of participants who achieved a complete response or partial response after initiation of the treatment and prior to initiation of subsequent systemic anti-lymphoma therapy. A CR = complete metabolic response; Target nodes/nodal masses regressed on computed tomography to (≤ 1.5 cm in their greatest transverse diameter for nodes \> 1.5 cm prior to therapy. Regressed to normal size by imaging, and absence of nodules related to lymphoma. If bone marrow was involved prior to therapy, no evidence of fluorodeoxyglucose avid disease in marrow. PR = ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. No increase in other nodes, liver, or spleen. Splenic nodules regressed by ≥ 50% in their SPD or for single nodules, in the greatest transverse diameter; no new lesions. Participants who did not have any adequate response assessments during this period were not considered as responders.
K-M Estimate of Duration of Complete Response From randomization date up to the data cut off date of 15 March 2019; median follow-up was 24.5 months. Duration of complete response was calculated for complete responders only and was defined as the time from documented initial complete response prior to initiation of subsequent systemic antilymphoma therapy until documented disease progression or death, whichever occurred earlier. Participants who had not progressed or died at the time of the analysis were censored at the date of last response assessment demonstrating no disease progression. Participants who changed treatment without evidence of disease progression were censored at the last assessment showing no progression prior to treatment change.
Mean Change From Baseline in the FACT-Lym Additional Concerns Subscale Baseline and Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34 The FACT-Lym questionnaire is a validated instrument for assessing the impact of lymphoma on HRQL and contains 42 questions covering HRQL and common lymphoma symptoms and treatment side-effects. It begins with the Functional Assessment of Cancer Therapy - General (FACT-G), which contains 27 questions covering four core subscales: Physical Wellbeing (7 items), Social/Family Wellbeing (7), Emotional Wellbeing (6), and Functional Wellbeing (7). The FACT-Lym also includes an Additional Concerns subscale (15 questions) used to assess NHL-related symptoms such as pain, itching, night sweats,trouble sleeping, fatigue and trouble concentrating and concerns regarding lumps and swelling, fevers, infections, weight, appetite, emotional stability and treatment. All questions are answered on a 5-point scale ranging from "not at all" (0) to "very much" (4). The Additional Concerns subscale ranges from 0 to 60, where higher scores reflect better HRQoL.
Mean Change From Baseline in the FACT-Lym Physical Well-Being Subscale Baseline and Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34 The FACT-Lym questionnaire is a validated instrument for assessing the impact of lymphoma on HRQL and contains 42 questions covering HRQL and common lymphoma symptoms and treatment side-effects. It begins with the Functional Assessment of Cancer Therapy - General (FACT-G), which contains 27 questions covering four core subscales: Physical Wellbeing (7 items), Social/Family Wellbeing (7), Emotional Wellbeing (6), and Functional Wellbeing (7). The FACT-Lym also includes an Additional Concerns subscale (15 questions) used to assess NHL-related symptoms and concerns. All questions are answered on a 5-point scale ranging from "not at all" (0) to "very much" (4). The physical well-being subscale ranges from 0 to 28, where higher scores reflect better HRQoL.
Mean Change From Baseline in the FACT-Lym Trial Outcome Index (TOI) Baseline and Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34 The FACT-Lym questionnaire is a validated instrument for assessing the impact of lymphoma on HRQL and contains 42 questions covering HRQL and common lymphoma symptoms and treatment side-effects. It begins with the Functional Assessment of Cancer Therapy - General (FACT-G), which contains 27 questions covering four core subscales: Physical Wellbeing (7 items), Social/Family Wellbeing (7), Emotional Wellbeing (6), and Functional Wellbeing (7). The FACT-Lym also includes an Additional Concerns subscale (15 questions) used to assess NHL-related symptoms and concerns. All questions are answered on a 5-point scale ranging from "not at all" (0) to "very much" (4). The FACT-Lym TOI is calculated by summing the Physical Well-being, Functional Well-being and Additional Concerns scores and has a range of 0 to 116. Higher scores reflect better HRQoL or fewer symptoms.
Mean Change From Baseline in the Euroqol 5-Dimension 3-Level (EQ-5D-3L) Index Score Baseline and Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34 The EQ-5D-3L is a generic, self-reported preference-based measure of health across five dimensions: mobility, self-care, pain, usual activities, and anxiety/depression. Each dimension has three levels of 'severity' corresponding to "no problems", "some problems" and "extreme problems". The instrument is scored as a single summary index using one of the available EQ-5D-3L value sets; in this study the UK scoring weights 9 were used. The UK index ranges from -0.594 to 1, where 0 equates to death and 1 equates to full health (-0.594 is considered 'worse than death').
Mean Change From Baseline in the EQ-5D-3L Visual Analogue Scale (VAS) Baseline and Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34 The EQ-5D-3L questionnaire includes a visual analogue scale which records the respondent's self-rated health on a vertical, 0-100 scale where 100 = "Best imaginable health state" and 0 = "Worst imaginable health state". Higher scores again indicate better HRQoL and positive change scores indicate that post screening values were higher than those observed at screening. The EQ-5D-3L is a generic, self-reported preference-based measure of health across five dimensions: mobility, self-care, pain, usual activities, and anxiety/depression. Each dimension has three levels of 'severity' corresponding to "no problems", "some problems" and "extreme problems".
K-M Estimate of Time to Next Lymphoma Therapy (TTNLT) From randomization date up to the data cut off date of 15 March 2019; median follow-up was 24.5 months Time to next lymphoma therapy was defined as the time from randomization to the time of treatment change for the next lymphoma treatment. Participants without treatment change were censored at date last known alive. Pre-specified optional therapies such as the extra 2 doses of single agent rituximab after Cycle 6 or consolidation radiotherapy did not count as treatment change for the next lymphoma therapy if the decision to treat and the location to be treated were determined prior to randomization.
Percentage of Participants Who Completed the Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym) Questionnaire Screening, Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34 The completion rate for FACT-Lym assessments was judged by looking at the number of completed FACT-Lym assessments at each time point. The FACT-Lym was considered completed if at least 1 calculable score was present. Completion rates were calculated as the number and percentage of participants out of the total number of patients in the ITT population and summarized by visit/cycle and treatment group. The FACT-Lym is a health related quality of life (HRQoL) questionnaire targeted to the management of chronic illness, predominantly within oncology and is considered an extension of the FACT-General questionnaire.
Mean Change From Baseline in the FACT-Lym Functional Well-Being Subscale Baseline and Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34 The FACT-Lym questionnaire is a validated instrument for assessing the impact of lymphoma on HRQL and contains 42 questions covering HRQL and common lymphoma symptoms and treatment side-effects. It begins with the Functional Assessment of Cancer Therapy - General (FACT-G), which contains 27 questions covering four core subscales: Physical Wellbeing (7 items), Social/Family Wellbeing (7), Emotional Wellbeing (6), and Functional Wellbeing (7). The FACT-Lym also includes an Additional Concerns subscale (15 questions) used to assess NHL-related symptoms and concerns. All questions are answered on a 5-point scale ranging from "not at all" (0) to "very much" (4). The functional well-being subscale ranges from 0 to 28, where higher scores reflect better HRQoL.
Trial Locations
- Locations (158)
Local Institution - 151
🇺🇸Dallas, Texas, United States
Siouxland Hematology-Oncology Associates, LLP
🇺🇸Sioux City, Iowa, United States
Local Institution - 161
🇺🇸Philadelphia, Pennsylvania, United States
Local Institution - 162
🇺🇸Seattle, Washington, United States
Local Institution - 101
🇺🇸Minneapolis, Minnesota, United States
Local Institution - 143
🇺🇸Fairway, Kansas, United States
Local Institution - 583
🇫🇷Montpellier, France
Local Institution - 652
🇮🇹Genova, Italy
Local Institution - 729
🇵🇹Lisboa, Portugal
Local Institution - 435
🇹🇷Denizli, Turkey
Local Institution - 275
🇮🇱Kfar-Saba, Israel
Local Institution - 277
🇮🇱Petach Tikva, Israel
Local Institution - 353
🇳🇱s-Hertogenbosch, Netherlands
Local Institution - 432
🇹🇷Istanbul, Turkey
Local Institution - 112
🇺🇸Rochester, Minnesota, United States
Center For Cancer And Blood Disorders
🇺🇸Bethesda, Maryland, United States
Local Institution - 177
🇺🇸Fayetteville, Arkansas, United States
Local Institution - 128
🇺🇸Hollywood, Florida, United States
Local Institution - 136
🇺🇸Orange, California, United States
McFarland Clinic
🇺🇸Ames, Iowa, United States
Local Institution - 158
🇺🇸Shreveport, Louisiana, United States
Local Institution - 138
🇺🇸Minneapolis, Minnesota, United States
Local Institution - 103
🇺🇸Durham, North Carolina, United States
Local Institution - 905
🇺🇸Edmonds, Washington, United States
Local Institution - 146
🇺🇸Salt Lake City, Utah, United States
Local Institution - 003
🇦🇺Frankston, Australia
Local Institution - 903
🇺🇸Issaquah, Washington, United States
Local Institution - 904
🇺🇸Seattle, Washington, United States
Local Institution - 002
🇦🇺Geelong, Victoria, Australia
Local Institution - 008
🇦🇺Clayton, Victoria, Australia
Local Institution - 301
🇧🇪Brussels, Belgium
Local Institution - 004
🇦🇺Albury, New South Wales, Australia
Local Institution - 307
🇧🇪Liege, Belgium
Local Institution - 303
🇧🇪Sint-Niklaas, Belgium
Local Institution - 305
🇧🇪Roeselare, Belgium
Local Institution - 368
🇨🇦Calgary, Alberta, Canada
Local Institution - 373
🇨🇦Surrey, British Columbia, Canada
Local Institution - 366
🇨🇦Saint John, New Brunswick, Canada
Local Institution - 362
🇨🇦Greenfield Park, Quebec, Canada
Local Institution - 206
🇨🇳Beijing, China
Local Institution - 365
🇨🇦Montreal, Quebec, Canada
Local Institution - 209
🇨🇳Beijing, China
Local Institution - 211
🇨🇳Changchun, China
Local Institution - 215
🇨🇳Beijing, China
Local Institution - 200
🇨🇳Beijing, China
Local Institution - 210
🇨🇳Chengdu, China
Local Institution - 213
🇨🇳Chongqing, China
Local Institution - 217
🇨🇳Guangzhou, Guangdong, China
Local Institution - 204
🇨🇳Hangzhou, China
Local Institution - 202
🇨🇳Fuzhou, China
Local Institution - 207
🇨🇳Harbin, Heilongjiang, China
Local Institution - 205
🇨🇳Nanjing, Jiangsu, China
Local Institution - 219
🇨🇳Suzhu, China
Local Institution - 214
🇨🇳Shanghai, China
Local Institution - 221
🇨🇳Tianjin, China
Local Institution - 379
🇨🇿Olomouc, Czechia
Local Institution - 376
🇨🇿Brno, Czechia
Local Institution - 377
🇨🇿Hradec Kralove, Czechia
Local Institution - 378
🇨🇿Praha, Czechia
Local Institution - 380
🇨🇿Prague 10, Czechia
Local Institution - 585
🇫🇷Bordeaux, France
Local Institution - 582
🇫🇷Paris, France
Local Institution - 588
🇫🇷Pessac Cedex, France
Local Institution - 587
🇫🇷Toulose, France
Local Institution - 581
🇫🇷Vandoeuvre les Nancy, France
Local Institution - 893
🇮🇪Dublin 4, Ireland
Local Institution - 894
🇮🇪Galway, Ireland
Local Institution - 273
🇮🇱Beer-Sheva, Israel
Local Institution - 272
🇮🇱Jerusalem, Israel
Local Institution - 274
🇮🇱Haifa, Israel
Local Institution - 686
🇮🇹Pagani, Italy
Local Institution - 270
🇮🇱Zerifin, Israel
Local Institution - 690
🇮🇹Terni, Umbria, Italy
Local Institution - 658
🇮🇹Brescia, Italy
Local Institution - 278
🇮🇱Tel-Aviv, Israel
Local Institution - 659
🇮🇹Allessandria, Italy
Local Institution - 674
🇮🇹Cuneo, Italy
Local Institution - 667
🇮🇹Ivrea, Italy
Local Institution - 653
🇮🇹Milano, Italy
Local Institution - 664
🇮🇹Firenze, Italy
Local Institution - 666
🇮🇹Milano, Italy
Local Institution - 684
🇮🇹Meldola, Italy
Local Institution - 676
🇮🇹Milano, Italy
Local Institution - 657
🇮🇹Napoli, Campania, Italy
Local Institution - 685
🇮🇹Padova, Italy
Local Institution - 655
🇮🇹Novara, Italy
Local Institution - 683
🇮🇹Rimini, Italy
Local Institution - 679
🇮🇹Ravenna, Italy
Local Institution - 651
🇮🇹Pavia, Italy
Local Institution - 673
🇮🇹Roma, Italy
Local Institution - 668
🇮🇹Reggio Emilia, Italy
Local Institution - 689
🇮🇹Roma, Italy
Local Institution - 694
🇮🇹Roma, Italy
Local Institution - 656
🇮🇹Rome, Italy
Local Institution - 662
🇮🇹Torino, Italy
Local Institution - 671
🇮🇹Torino, Italy
Local Institution - 682
🇮🇹Verona, Italy
Local Institution - 692
🇮🇹Udine, Italy
Local Institution - 681
🇮🇹Tricase, Italy
Local Institution - 502
🇯🇵Minato-ku, Tokyo, Japan
Local Institution - 672
🇮🇹Vicenza, Italy
Local Institution - 508
🇯🇵Chuo-ku, Tokyo, Japan
Local Institution - 509
🇯🇵Koto-ku, Tokyo, Japan
Local Institution - 511
🇯🇵Fukuoka, Japan
Local Institution - 505
🇯🇵Isehara City, Kanagawa, Japan
Local Institution - 506
🇯🇵Minami-Ku, Fukuoka, Japan
Local Institution - 513
🇯🇵Akita-shi, Japan
Local Institution - 501
🇯🇵Kashiwa, Japan
Local Institution - 510
🇯🇵Kyoto-City, Japan
Local Institution - 507
🇯🇵Nagoya, Japan
Local Institution - 504
🇯🇵Yamagata, Japan
Local Institution - 515
🇯🇵Sendai-city, Japan
Local Institution - 829
🇰🇷Seoul, Korea, Republic of
Local Institution - 830
🇰🇷Gyeonggi-do, Korea, Republic of
Local Institution - 357
🇳🇱Hoofddorp, Netherlands
Local Institution - 826
🇰🇷Seoul, Korea, Republic of
Local Institution - 358
🇳🇱Amsterdam, Netherlands
Local Institution - 354
🇳🇱Leeuwarden, Netherlands
Local Institution - 359
🇳🇱Breda, Netherlands
Local Institution - 243
🇳🇿Palmerston, New Zealand
Local Institution - 350
🇳🇱Schiedam, Netherlands
Local Institution - 240
🇳🇿Christchurch, New Zealand
Local Institution - 732
🇵🇹Lisboa, Portugal
Local Institution - 730
🇵🇹Figueira da Foz, Portugal
Local Institution - 115
🇵🇷San Juan, Puerto Rico
Local Institution - 050
🇷🇺Kazan, Russian Federation
Local Institution - 776
🇪🇸Barcelona, Spain
Local Institution - 727
🇵🇹Pragal, Portugal
Local Institution - 052
🇷🇺Moscow, Russian Federation
Local Institution - 051
🇷🇺St. Petersburg, Russian Federation
Local Institution - 783
🇪🇸Madrid, Spain
Local Institution - 796
🇪🇸Caceres, Spain
Local Institution - 780
🇪🇸Barcelona, Spain
Local Institution - 785
🇪🇸Madrid, Spain
Local Institution - 787
🇪🇸Madrid, Spain
Local Institution - 788
🇪🇸Madrid, Spain
Local Institution - 790
🇪🇸Sevilla, Spain
Local Institution - 793
🇪🇸Valencia, Spain
Local Institution - 323
🇨🇭Bellinzona, Switzerland
Local Institution - 321
🇨🇭Winterthur, Switzerland
Local Institution - 800
🇪🇸Sevilla, Spain
Local Institution - 253
🇨🇳Niao-Sung Hsiang Kaohsiung County, Taiwan
Local Institution - 320
🇨🇭Geneva, Switzerland
Local Institution - 431
🇹🇷Ankara, Turkey
Local Institution - 255
🇨🇳Taichung City, Taiwan
Local Institution - 252
🇨🇳Taipei, Zhongzheng Dist., Taiwan
Local Institution - 430
🇹🇷Antalya, Turkey
Local Institution - 797
🇪🇸Salamanca, Spain
Local Institution - 127
🇺🇸Sacramento, California, United States
Local Institution - 802
🇪🇸Valencia, Spain
Local Institution - 951
🇺🇸Dallas, Texas, United States
Local Institution - 203
🇨🇳Wuhan, China
Local Institution - 576
🇫🇷Bayonne, France
Local Institution - 828
🇰🇷Seoul, Korea, Republic of
Local Institution - 428
🇹🇷Edirne, Turkey
Local Institution - 429
🇹🇷Adana, Turkey
Local Institution - 169
🇺🇸New Haven, Connecticut, United States
Local Institution - 212
🇨🇳Nanjing, China