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

NCT ID: NCT02285062

Last Updated: 2023-06-22

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

570 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-02-17

Study Completion Date

2022-07-28

Brief Summary

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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

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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.

Conditions

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Lymphoma, Large B-Cell, Diffuse

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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R2-CHOP

Lenalidomide plus R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)

Group Type EXPERIMENTAL

lenalidomide

Intervention Type DRUG

Rituximab

Intervention Type DRUG

Cyclophosphamide

Intervention Type DRUG

Doxorubicin

Intervention Type DRUG

prednisone

Intervention Type DRUG

vincristine

Intervention Type DRUG

R-CHOP

Placebo plus R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)

Group Type ACTIVE_COMPARATOR

Placebo

Intervention Type DRUG

Rituximab

Intervention Type DRUG

Cyclophosphamide

Intervention Type DRUG

Doxorubicin

Intervention Type DRUG

prednisone

Intervention Type DRUG

vincristine

Intervention Type DRUG

Interventions

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lenalidomide

Intervention Type DRUG

Placebo

Intervention Type DRUG

Rituximab

Intervention Type DRUG

Cyclophosphamide

Intervention Type DRUG

Doxorubicin

Intervention Type DRUG

prednisone

Intervention Type DRUG

vincristine

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Histologically proven Diffuse Large B-Cell Lymphoma of the Activated B-Cell type
2. Newly diagnosed, previously untreated Diffuse Large B-Cell Lymphoma
3. Measurable Diffuse Large B-Cell Lymphoma disease by Computed Tomography (CT) / Magnetic Resonance Imagining (MRI) scans
4. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
5. 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)

Exclusion Criteria

1. Diagnosis of lymphoma histologies other than Diffuse Large B-Cell Lymphoma
2. History of malignancies, other than Diffuse Large B-Cell Lymphoma, unless the patient has been disease free for 5 years or more
3. Known seropositive for, or history of, active Human Immunodeficiency Virus (HIV) Hepatitis B Virus (HBV), Hepatitis C Virus (HCV)
4. Contraindication to any drug in the chemotherapy regimen, and specifically: LVEF (Left Ventricular Ejection Fraction) \< 45% or peripheral neuropathy grade 2
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Celgene

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

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Local Institution - 177

Fayetteville, Arkansas, United States

Site Status

Local Institution - 136

Orange, California, United States

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Local Institution - 127

Sacramento, California, United States

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Local Institution - 169

New Haven, Connecticut, United States

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Local Institution - 128

Hollywood, Florida, United States

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McFarland Clinic

Ames, Iowa, United States

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Siouxland Hematology-Oncology Associates, LLP

Sioux City, Iowa, United States

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Local Institution - 143

Fairway, Kansas, United States

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Local Institution - 158

Shreveport, Louisiana, United States

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Center For Cancer And Blood Disorders

Bethesda, Maryland, United States

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Local Institution - 101

Minneapolis, Minnesota, United States

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Local Institution - 138

Minneapolis, Minnesota, United States

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Local Institution - 112

Rochester, Minnesota, United States

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Local Institution - 103

Durham, North Carolina, United States

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Local Institution - 161

Philadelphia, Pennsylvania, United States

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Local Institution - 951

Dallas, Texas, United States

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Local Institution - 151

Dallas, Texas, United States

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Local Institution - 146

Salt Lake City, Utah, United States

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Local Institution - 905

Edmonds, Washington, United States

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Local Institution - 903

Issaquah, Washington, United States

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Local Institution - 162

Seattle, Washington, United States

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Local Institution - 904

Seattle, Washington, United States

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Local Institution - 004

Albury, New South Wales, Australia

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Local Institution - 008

Clayton, Victoria, Australia

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Local Institution - 002

Geelong, Victoria, Australia

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Local Institution - 003

Frankston, , Australia

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Local Institution - 301

Brussels, , Belgium

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Local Institution - 307

Liège, , Belgium

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Local Institution - 305

Roeselare, , Belgium

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Local Institution - 303

Sint-Niklaas, , Belgium

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Local Institution - 368

Calgary, Alberta, Canada

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Local Institution - 373

Surrey, British Columbia, Canada

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Local Institution - 366

Saint John, New Brunswick, Canada

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Local Institution - 362

Greenfield Park, Quebec, Canada

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Local Institution - 365

Montreal, Quebec, Canada

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Local Institution - 209

Beijing, , China

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Local Institution - 206

Beijing, , China

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Local Institution - 215

Beijing, , China

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Local Institution - 200

Beijing, , China

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Local Institution - 211

Changchun, , China

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Local Institution - 210

Chengdu, , China

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Local Institution - 213

Chongqing, , China

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Local Institution - 202

Fuzhou, , China

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Local Institution - 217

Guangzhou, Guangdong, , China

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Local Institution - 204

Hangzhou, , China

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Local Institution - 207

Harbin, Heilongjiang, , China

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Local Institution - 212

Nanjing, , China

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Local Institution - 205

Nanjing, Jiangsu, , China

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Local Institution - 214

Shanghai, , China

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Local Institution - 219

Suzhu, , China

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Local Institution - 221

Tianjin, , China

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Local Institution - 203

Wuhan, , China

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Brno, , Czechia

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Local Institution - 377

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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Local Institution - 576

Bayonne, , France

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Local Institution - 585

Bordeaux, , France

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Local Institution - 583

Montpellier, , France

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Paris, , France

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Local Institution - 588

Pessac, , France

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Local Institution - 587

Toulose, , France

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Vandœuvre-lès-Nancy, , France

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Local Institution - 893

Dublin, , Ireland

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Local Institution - 894

Galway, , Ireland

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Local Institution - 273

Beersheba, , Israel

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Local Institution - 274

Haifa, , Israel

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Local Institution - 272

Jerusalem, , Israel

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Kfar Saba, , Israel

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Petah Tikva, , Israel

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Tel Aviv, , Israel

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Ẕerifin, , Israel

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Terni, Umbria, Italy

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Allessandria, , Italy

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Brescia, , Italy

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Cuneo, , Italy

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Florence, , Italy

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Genova, , Italy

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Ivrea, , Italy

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Meldola, , Italy

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Milan, , Italy

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Milan, , Italy

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Milan, , Italy

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Napoli, Campania, , Italy

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Novara, , Italy

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Padua, , Italy

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Pagani, , Italy

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Pavia, , Italy

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Ravenna, , Italy

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Reggio Emilia, , Italy

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Rimini, , Italy

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Roma, , Italy

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Roma, , Italy

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Roma, , Italy

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Rome, , Italy

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Torino, , Italy

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Torino, , Italy

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Tricase, , Italy

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Local Institution - 692

Udine, , Italy

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Verona, , Italy

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Vicenza, , Italy

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Local Institution - 508

Chuo-ku, Tokyo, Japan

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Local Institution - 509

Koto-ku, Tokyo, Japan

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Local Institution - 502

Minato-ku, Tokyo, Japan

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Local Institution - 513

Akita, , Japan

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Local Institution - 511

Fukuoka, , Japan

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Local Institution - 505

Isehara City, Kanagawa, , Japan

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Kashiwa, , Japan

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Kyoto, , Japan

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Minami-Ku, Fukuoka, , Japan

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Nagoya, , Japan

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Sendai, , Japan

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Yamagata, , Japan

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's-Hertogenbosch, , Netherlands

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Amsterdam, , Netherlands

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Breda, , Netherlands

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Hoofddorp, , Netherlands

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Leeuwarden, , Netherlands

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Schiedam, , Netherlands

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Christchurch, , New Zealand

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Palmerston, , New Zealand

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Figueira da Foz Municipality, , Portugal

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Lisbon, , Portugal

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Lisbon, , Portugal

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Pragal, , Portugal

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San Juan, , Puerto Rico

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Kazan', , Russia

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Moscow, , Russia

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Saint Petersburg, , Russia

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Gyeonggi-do, , 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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Local Institution - 776

Barcelona, , Spain

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Local Institution - 780

Barcelona, , Spain

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Cáceres, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Salamanca, , Spain

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Local Institution - 790

Seville, , Spain

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Local Institution - 800

Seville, , Spain

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Local Institution - 793

Valencia, , Spain

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Local Institution - 802

Valencia, , Spain

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Local Institution - 323

Bellinzona, , Switzerland

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Local Institution - 320

Geneva, , Switzerland

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Local Institution - 321

Winterthur, , Switzerland

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Local Institution - 253

Niao-Sung Hsiang Kaohsiung County, , Taiwan

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Local Institution - 255

Taichung, , Taiwan

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Local Institution - 252

Taipei, Zhongzheng Dist., , Taiwan

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Local Institution - 429

Adana, , Turkey (Türkiye)

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Local Institution - 431

Ankara, , Turkey (Türkiye)

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Local Institution - 430

Antalya, , Turkey (Türkiye)

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Local Institution - 435

Denizli, , Turkey (Türkiye)

Site Status

Local Institution - 428

Edirne, , Turkey (Türkiye)

Site Status

Local Institution - 432

Istanbul, , Turkey (Türkiye)

Site Status

Countries

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United States Australia Belgium Canada China Czechia France Ireland Israel Italy Japan Netherlands New Zealand Portugal Puerto Rico Russia South Korea Spain Switzerland Taiwan Turkey (Türkiye)

References

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Nowakowski GS, Chiappella A, Witzig TE, Spina M, Gascoyne RD, Zhang L, Flament J, Repici J, Vitolo U. ROBUST: Lenalidomide-R-CHOP versus placebo-R-CHOP in previously untreated ABC-type diffuse large B-cell lymphoma. Future Oncol. 2016 Jul;12(13):1553-63. doi: 10.2217/fon-2016-0130. Epub 2016 Apr 18.

Reference Type BACKGROUND
PMID: 27089170 (View on PubMed)

Alfaifi A, Bahashwan S, Alsaadi M, Ageel AH, Ahmed HH, Fatima K, Malhan H, Qadri I, Almehdar H. Advancements in B-Cell Non-Hodgkin's Lymphoma: From Signaling Pathways to Targeted Therapies. Adv Hematol. 2024 Nov 12;2024:5948170. doi: 10.1155/2024/5948170. eCollection 2024.

Reference Type DERIVED
PMID: 39563886 (View on PubMed)

Nowakowski GS, Chiappella A, Gascoyne RD, Scott DW, Zhang Q, Jurczak W, Ozcan M, Hong X, Zhu J, Jin J, Belada D, Bergua JM, Piazza F, Mocikova H, Molinari AL, Yoon DH, Cavallo F, Tani M, Yamamoto K, Izutsu K, Kato K, Czuczman M, Hersey S, Kilcoyne A, Russo J, Hudak K, Zhang J, Wade S, Witzig TE, Vitolo U. ROBUST: A Phase III Study of Lenalidomide Plus R-CHOP Versus Placebo Plus R-CHOP in Previously Untreated Patients With ABC-Type Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2021 Apr 20;39(12):1317-1328. doi: 10.1200/JCO.20.01366. Epub 2021 Feb 23.

Reference Type DERIVED
PMID: 33621109 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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2013-004054-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CC-5013-DLC-002

Identifier Type: -

Identifier Source: org_study_id

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