A Trial to Evaluate the Efficacy and Safety of Tafasitamab With Bendamustine (BEN) Versus Rituximab (RTX) With BEN in Adult Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)

NCT ID: NCT02763319

Last Updated: 2025-07-17

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

453 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-11-28

Study Completion Date

2024-06-21

Brief Summary

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The purpose of the study is to compare the safety and efficacy of Tafasitamab with BEN versus RTX with BEN in adult patients with relapsed of refractory DLBCL.

Detailed Description

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This is a randomised, two-arm, multicentre, open-label phase II/III efficacy and safety study of Tafasitamab in combination with BEN versus RTX in combination with BEN given to adult patients who have relapsed after or are refractory to at least one but no more than three prior systemic therapies and have failed, or are not candidates for HDC and ASCT, and have thus exhausted their therapeutic options of demonstrated clinical benefit. At least one prior therapy line must have included a CD20-targeted therapy.

Conditions

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Diffuse Large B-cell Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
Outcome assessor: blinding on treatment group

Study Groups

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Tafasitamab and bendamustine

Tafasitamab and bendamustine

Group Type EXPERIMENTAL

Tafasitamab

Intervention Type DRUG

Tafasitamab: Tafasitamab dose: 12 mg/kg intravenously (IV)

Bendamustine (BEN)

Intervention Type DRUG

Rituximab and bendamustine

Rituximab and bendamustine

Group Type ACTIVE_COMPARATOR

Rituximab (RTX)

Intervention Type DRUG

Rituximab: Dose: 375 mg/m2 IV

Bendamustine (BEN)

Intervention Type DRUG

Interventions

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Rituximab (RTX)

Rituximab: Dose: 375 mg/m2 IV

Intervention Type DRUG

Tafasitamab

Tafasitamab: Tafasitamab dose: 12 mg/kg intravenously (IV)

Intervention Type DRUG

Bendamustine (BEN)

Intervention Type DRUG

Other Intervention Names

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Rituxan Mab Thera Levact/Treanda

Eligibility Criteria

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Inclusion Criteria

1. Age ≥18 years
2. Histologically confirmed diagnosis, according to the World Health Organization (WHO, 2008) classification, of: DLBCL NOS, THRLBCL, EBV-positive DLBCL, composite lymphoma with a DLBCL component with a DLBCL relapse subsequent to DLBCL treatment, disease transformed from an earlier diagnosis of low grade lymphoma (i.e. an indolent pathology such as follicular lymphoma, marginal zone lymphoma) into DLBCL with a DLBCL relapse subsequent to DLBCL treatment.
3. Fresh tumour tissue for central pathology review must be provided as an adjunct to participation in this study. Should it not be possible to obtain a fresh tumour tissue sample, archival paraffin embedded tumour tissue acquired ≤3 years prior to screening for this protocol must be available for this purpose.
4. Patients must have:

1. relapsed or refractory DLBCL
2. at least one bidimensionally measurable disease site. The lesion must have a greatest transverse diameter of ≥1.5 cm and greatest perpendicular diameter of ≥1.0 cm at baseline. The lesion must be positive on PET scan
3. received at least one, but no more than three previous systemic therapy lines for the treatment of DLBCL. At least one previous therapy line must have included a CD20-targeted.
4. ECOG 0 to 2
5. Patients after failure of ASCT or patients considered in the opinion of the investigator currently not eligible for HDC with subsequent ASCT.
6. Patients must meet the following laboratory criteria at Screening:

1. ANC ≥1.5 × 109/L (unless secondary to bone marrow involvement by DLBCL)
2. PLTs ≥90 × 109/L (unless secondary to bone marrow involvement by DLBCL) and absence of active bleeding
3. total serum bilirubin ≤2.5 × ULN unless secondary to Gilbert's syndrome (or pattern consistent with Gilbert's) or documented liver involvement by lymphoma. Patients with Gilbert's syndrome or documented liver involvement by lymphoma may be included if their total bilirubin is ≤5 x ULN
4. ALT, AST and AP ≤3 × ULN or \<5 × ULN in cases of documented liver involvement by lymphoma
5. serum creatinine ≤2.0 x ULN or creatinine clearance must be ≥40 mL/min calculated using a standard Cockcroft-Gault formula (Cockroft \& Gault, 1976)
7. For a female of childbearing potential (FCBP), a negative pregnancy test must be confirmed before enrolment. An FCBP must commit to take highly effective contraceptive precautions without interruption during the study and for 3, 6 or 12 months after the last dose of Tafasitamab, BEN or RTX respectively, whichever is later. An FCBP must refrain from breastfeeding and donating blood or oocytes during the course of the study and for 3, 6 or 12 months after the last dose of Tafasitamab, BEN or RTX respectively, whichever is later. Restrictions concerning blood donations apply as well to females who are not of childbearing potential.
8. Males must use an effective barrier method of contraception without interruption during the study and for 3, 6 or 12 months after the last dose of Tafasitamab, BEN or RTX respectively, whichever is later, if the patient is sexually active with an FCBP. Males must refrain from donating blood or sperm during study participation and for 3, 6 or 12 months after the last dose of Tafasitamab, BEN or RTX respectively, whichever is later.
9. In the opinion of the investigator, the patients must:

1. be able to comply with all study-related procedures, medication use, and evaluations
2. be able to understand and give informed consent
3. not be considered to be potentially unreliable and/or not cooperative.

Exclusion Criteria

1. Patients who have: any other histological type of lymphoma including, e.g., primary mediastinal (thymic) large B-cell lymphoma (PMBL) or Burkitt's lymphoma, primary refractory DLBCL, patients with known "double/triple hit" DLBCL genetics, CNS lymphoma involvement in present or past medical history
2. Patients who had a major surgery less than 30 days prior to Day 1 dosing
3. Patients who have, within 14 days prior to Day 1 dosing:

1. not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy or other lymphoma-specific therapy
2. received live vaccines
3. required parenteral antimicrobial therapy for active, intercurrent systemic infections
4. Patients who:

1. in the opinion of the investigator, have not recovered sufficiently from the adverse toxic effects of prior therapies, major surgeries or significant traumatic injuries
2. were previously treated with CD19-targeted therapy or BEN
3. have a history of previous severe allergic reactions to compounds of similar biological or chemical composition to Tafasitamab, RTX, murine proteins or BEN, or the excipients contained in the study drug formulations
4. have undergone ASCT within a period of ≤3 months prior to signing the informed consent form. Patients who have a more distant history of ASCT must exhibit full haematological recovery before enrolment into the study.
5. have undergone previous allogeneic stem cell transplantation
6. concurrently use other anticancer or experimental treatments
5. Prior history of malignancies other than DLBCL, unless the patient has been free of the disease for ≥3 years prior to Screening. Exceptions to the ≥3-year time limit include history of the following:

1. basal cell carcinoma of the skin
2. squamous cell carcinoma of the skin
3. carcinoma in situ of the cervix, breast and bladder

f) incidental histological finding of prostate cancer (Tumour/Node/Metastasis \[TNM\] stage of T1a or T1b)
6. Patients with:

1. positive hepatitis B and/or C serology
2. known seropositivity for or history of active viral infection with HIV
3. evidence of active, severe uncontrolled systemic infections or sepsis
4. a history or evidence of severely immunocompromised state
5. a history or evidence of severe hepatic impairment (total serum bilirubin \> 3 mg/dL), jaundice unless secondary to Gilbert's syndrome or documented liver involvement by lymphoma
6. a history or evidence of clinically significant cardiovascular, cerebrovascular, CNS and/or other disease that, in the investigator's opinion, would preclude participation in the study or compromise the patient's ability to give informed consent
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Incyte Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Incyte Medical Director

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

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MorphoSys Research Site

Anaheim, California, United States

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Bakersfield, California, United States

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Burbank, California, United States

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Fresno, California, United States

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Los Angeles, California, United States

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Whittier, California, United States

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Plainville, Connecticut, United States

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Skokie, Illinois, United States

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Detroit, Michigan, United States

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Rochester, Minnesota, United States

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Hattiesburg, Mississippi, United States

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Jackson, Mississippi, United States

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Morristown, New Jersey, United States

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New York, New York, United States

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Stony Brook, New York, United States

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Oklahoma City, Oklahoma, United States

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Knoxville, Tennessee, United States

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Lubbock, Texas, United States

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Adelaide, , Australia

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Albury, , Australia

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Bedford Park, , Australia

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Box Hill, , Australia

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Concord, , Australia

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Frankston, , Australia

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Garran, , Australia

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Geelong, , Australia

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Gosford, , Australia

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Nedlands, , Australia

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South Brisbane, , Australia

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St Albans, , Australia

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Innsbruck, , Austria

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Edmonton, Alberta, Canada

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Winnipeg, Manitoba, Canada

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Saint John, New Brunswick, Canada

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St. John's, Newfoundland and Labrador, Canada

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Kingston, Ontario, Canada

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Greenfield Park, Quebec, Canada

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Montreal, Quebec, Canada

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Saskatoon, , Canada

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Zagreb, , Croatia

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Hradec Králové, , Czechia

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Olomouc, , Czechia

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Prague, , Czechia

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Prague, , Czechia

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Oulu, , Finland

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Tampere, , Finland

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Grenoble, , France

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Le Mans, , France

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Aachen, , Germany

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Berlin, , Germany

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Berlin, , Germany

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Düsseldorf, , Germany

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Giessen, , Germany

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Homburg, , Germany

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Leipzig, , Germany

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Mainz, , Germany

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Munich, , Germany

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Munich, , Germany

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Mutlangen, , Germany

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Münster, , Germany

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Rostock, , Germany

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Stuttgart, , Germany

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Stuttgart, , Germany

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Traunstein, , Germany

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Budapest, , Hungary

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Debrecen, , Hungary

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Győr, , Hungary

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Szeged, , Hungary

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Haifa, , Israel

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Jerusalem, , Israel

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Jerusalem, , Israel

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Kfar Saba, , Israel

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Tel Aviv, , Israel

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Alessandria, , Italy

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Bologna, , Italy

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Campobasso, , Italy

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Cona, , Italy

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Genova, , Italy

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Lecce, , Italy

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Meldola, , Italy

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Monza, , Italy

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Napoli, , Italy

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Novara, , Italy

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Orbassano, , Italy

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Parma, , Italy

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Pavia, , Italy

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Pisa, , Italy

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Ravenna, , Italy

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Reggio Emilia, , Italy

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Rimini, , Italy

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Rome, , Italy

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Rome, , Italy

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Terni, , Italy

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Turin, , Italy

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Turin, , Italy

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Addington, , New Zealand

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Auckland, , New Zealand

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Grafton, , New Zealand

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Bydgoszcz, , Poland

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Gdynia, , Poland

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Krakow, , Poland

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Legnica, , Poland

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Lodz, , Poland

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Lublin, , Poland

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Warsaw, , Poland

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Wroclaw, , Poland

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Braga, , Portugal

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Coimbra, , Portugal

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Coimbra, , Portugal

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Matosinhos Municipality, , Portugal

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Porto, , Portugal

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Porto, , Portugal

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Pragal, , Portugal

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Bucharest, , Romania

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Bucharest, , Romania

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Iași, , Romania

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Belgrade, , Serbia

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Kragujevac, , Serbia

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Singapore, , Singapore

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Singapore, , Singapore

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Singapore, , Singapore

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Singapore, , Singapore

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Busan, , South Korea

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Goyang-si, , South Korea

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Incheon, , South Korea

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Jeonju, , South Korea

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Seongnam, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Ulsan, , South Korea

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Cadiz, , Spain

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Girona, , Spain

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L'Hospitalet de Llobregat, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Palma de Mallorca, , Spain

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Pamplona, , Spain

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Pozuelo de Alarcón, , Spain

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Sabadell, , Spain

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Salamanca, , Spain

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Valencia, , Spain

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Chang-hua, , Taiwan

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Hualien City, , Taiwan

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Taichung, , Taiwan

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Adana, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Bornova, , Turkey (Türkiye)

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Gaziantep, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Manisa, , Turkey (Türkiye)

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Samsun, , Turkey (Türkiye)

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Birmingham, , United Kingdom

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Leeds, , United Kingdom

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Southend-on-Sea, , United Kingdom

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Countries

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United States Australia Austria Canada Croatia Czechia Finland France Germany Hungary Israel Italy New Zealand Poland Portugal Romania Serbia Singapore South Korea Spain Taiwan Turkey (Türkiye) United Kingdom

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2014-004689-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MOR208C204

Identifier Type: -

Identifier Source: org_study_id

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