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

NCT02285062 | Completed Phase 3 Results DMC

• 2 other identifiers: CC-5013-DLC-0022013-004054-21
• Study Type: interventional
• Target: 570
• Locations: 21 countries
• Sites: 158

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.

Conditions

Lymphoma, Large B-Cell, Diffuse

Keywords

R-CHOP chemotherapy; DLBCL front line therapy; gene expression profiling (GEP) activated B-cell (ABC) type DLBCL biomarkers; Activated B-Cell (ABC) type; Diffuse Large B-Cell Lymphoma, not otherwise specified; Diffuse Large B-Cell Lymphoma, associated with chronic inflammation; Diffuse Large B-Cell Lymphoma, Epstein-Barr virus positive (EBS+) of the elderly; Diffuse Large B-Cell Lymphoma, T-cell / histiocyte-rich

Outcome Measures

Primary Outcomes (1)

• Kaplan-Meier Estimate of Progression Free Survival (PFS)

  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.

  From the date of randomization up to the data cut off date of 15 March 2019; median follow-up of 24.5 months

Secondary Outcomes (14)

• 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

• K-M Estimate of Overall Survival (OS)

  From randomization until death due to any cause (up to approximately 86 months)

• 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

• 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

• 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.

Study Arms (2)

R2-CHOP

EXPERIMENTAL

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

Drug: lenalidomide; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: prednisone; Drug: vincristine

R-CHOP

ACTIVE COMPARATOR

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

Drug: Placebo; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: prednisone; Drug: vincristine

Interventions

lenalidomide DRUG

R2-CHOP

Placebo DRUG

R-CHOP

Rituximab DRUG

R-CHOP; R2-CHOP

Cyclophosphamide DRUG

R-CHOP; R2-CHOP

Doxorubicin DRUG

R-CHOP; R2-CHOP

prednisone DRUG

R-CHOP; R2-CHOP

vincristine DRUG

R-CHOP; R2-CHOP

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Celgene: lead

Study Sites (158)

Local Institution - 177

Fayetteville, Arkansas, 72703, United States

Location

Local Institution - 136

Orange, California, 92868, United States

Location

Local Institution - 127

Sacramento, California, 95817, United States

Location

Local Institution - 169

New Haven, Connecticut, 06510, United States

Location

Local Institution - 128

Hollywood, Florida, 33021, United States

Location

McFarland Clinic

Ames, Iowa, 50010-3014, United States

Location

Siouxland Hematology-Oncology Associates, LLP

Sioux City, Iowa, 51101-1733, United States

Location

Local Institution - 143

Fairway, Kansas, 66205, United States

Location

Local Institution - 158

Shreveport, Louisiana, 71103, United States

Location

Center For Cancer And Blood Disorders

Bethesda, Maryland, 20817, United States

Location

Local Institution - 101

Minneapolis, Minnesota, 55416, United States

Location

Local Institution - 138

Minneapolis, Minnesota, 55455, United States

Location

Local Institution - 112

Rochester, Minnesota, 55905, United States

Location

Local Institution - 103

Durham, North Carolina, 27710, United States

Location

Local Institution - 161

Philadelphia, Pennsylvania, 19111, United States

Location

Local Institution - 951

Dallas, Texas, 75235, United States

Location

Local Institution - 151

Dallas, Texas, 75390-9068, United States

Location

Local Institution - 146

Salt Lake City, Utah, 84106, United States

Location

Local Institution - 905

Edmonds, Washington, 98026, United States

Location

Local Institution - 903

Issaquah, Washington, 98029, United States

Location

Local Institution - 162

Seattle, Washington, 98104, United States

Location

Local Institution - 904

Seattle, Washington, 98107, United States

Location

Local Institution - 004

Albury, New South Wales, 2640, Australia

Location

Local Institution - 008

Clayton, Victoria, 3168, Australia

Location

Local Institution - 002

Geelong, Victoria, 3220, Australia

Location

Local Institution - 003

Frankston, 3199, Australia

Location

Local Institution - 301

Brussels, 1200, Belgium

Location

Local Institution - 307

Liège, 4000, Belgium

Location

Local Institution - 305

Roeselare, 8800, Belgium

Location

Local Institution - 303

Sint-Niklaas, 9100, Belgium

Location

Local Institution - 368

Calgary, Alberta, T2N 4N2, Canada

Location

Local Institution - 373

Surrey, British Columbia, V3T 0H1, Canada

Location

Local Institution - 366

Saint John, New Brunswick, E2L 3L6, Canada

Location

Local Institution - 362

Greenfield Park, Quebec, J4V 2H1, Canada

Location

Local Institution - 365

Montreal, Quebec, H1T 2M4, Canada

Location

Local Institution - 209

Beijing, 100044, China

Location

Local Institution - 206

Beijing, 100142, China

Location

Local Institution - 215

Beijing, 100191, China

Location

Local Institution - 200

Beijing, 100730, China

Location

Local Institution - 211

Changchun, 130021, China

Location

Local Institution - 210

Chengdu, 610041, China

Location

Local Institution - 213

Chongqing, 400037, China

Location

Local Institution - 202

Fuzhou, 350001, China

Location

Local Institution - 217

Guangzhou, Guangdong, 510080, China

Location

Local Institution - 204

Hangzhou, 310003, China

Location

Local Institution - 207

Harbin, Heilongjiang, 150081, China

Location

Local Institution - 212

Nanjing, 210029, China

Location

Local Institution - 205

Nanjing, Jiangsu, 210009, China

Location

Local Institution - 214

Shanghai, 200032, China

Location

Local Institution - 219

Suzhu, 215006, China

Location

Local Institution - 221

Tianjin, 300060, China

Location

Local Institution - 203

Wuhan, 430030, China

Location

Local Institution - 376

Brno, 625 00, Czechia

Location

Local Institution - 377

Hradec Králové, 500 05, Czechia

Location

Local Institution - 379

Olomouc, 775 20, Czechia

Location

Local Institution - 380

Prague, 100 34, Czechia

Location

Local Institution - 378

Prague, 128 08, Czechia

Location

Local Institution - 576

Bayonne, 64109, France

Location

Local Institution - 585

Bordeaux, 33076, France

Location

Local Institution - 583

Montpellier, 34295, France

Location

Local Institution - 582

Paris, 75010, France

Location

Local Institution - 588

Pessac, 33604, France

Location

Local Institution - 587

Toulose, 31059, France

Location

Local Institution - 581

Vandœuvre-lès-Nancy, 54511, France

Location

Local Institution - 893

Dublin, 4, Ireland

Location

Local Institution - 894

Galway, ST46QG, Ireland

Location

Local Institution - 273

Beersheba, 84101, Israel

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Local Institution - 274

Haifa, 31096, Israel

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Local Institution - 272

Jerusalem, 91120, Israel

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Local Institution - 275

Kfar Saba, 44281, Israel

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Local Institution - 277

Petah Tikva, 49100, Israel

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Local Institution - 278

Tel Aviv, 64239, Israel

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Local Institution - 270

Ẕerifin, 70300, Israel

Location

Local Institution - 690

Terni, Umbria, 05100, Italy

Location

Local Institution - 659

Allessandria, 15100, Italy

Location

Local Institution - 658

Brescia, 25123, Italy

Location

Local Institution - 674

Cuneo, 12100, Italy

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Local Institution - 664

Florence, 50134, Italy

Location

Local Institution - 652

Genova, 16132, Italy

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Local Institution - 667

Ivrea, 10015, Italy

Location

Local Institution - 684

Meldola, 47014, Italy

Location

Local Institution - 666

Milan, 20132, Italy

Location

Local Institution - 653

Milan, 20133, Italy

Location

Local Institution - 676

Milan, 20162, Italy

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Local Institution - 657

Napoli, Campania, 80131, Italy

Location

Local Institution - 655

Novara, 28100, Italy

Location

Local Institution - 685

Padua, 35128, Italy

Location

Local Institution - 686

Pagani, 84016, Italy

Location

Local Institution - 651

Pavia, 27100, Italy

Location

Local Institution - 679

Ravenna, 48121, Italy

Location

Local Institution - 668

Reggio Emilia, 42100, Italy

Location

Local Institution - 683

Rimini, 47900, Italy

Location

Local Institution - 689

Roma, 00128, Italy

Location

Local Institution - 694

Roma, 00161, Italy

Location

Local Institution - 673

Roma, 00189, Italy

Location

Local Institution - 656

Rome, 00152, Italy

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Local Institution - 671

Torino, 01012, Italy

Location

Local Institution - 662

Torino, 10126, Italy

Location

Local Institution - 681

Tricase, 73039, Italy

Location

Local Institution - 692

Udine, 33100, Italy

Location

Local Institution - 682

Verona, 37134, Italy

Location

Local Institution - 672

Vicenza, 36100, Italy

Location

Local Institution - 508

Chuo-ku, Tokyo, 104-0045, Japan

Location

Local Institution - 509

Koto-ku, Tokyo, 1358550, Japan

Location

Local Institution - 502

Minato-ku, Tokyo, 105-8470, Japan

Location

Local Institution - 513

Akita, 010-8543, Japan

Location

Local Institution - 511

Fukuoka, 812-8582, Japan

Location

Local Institution - 505

Isehara City, Kanagawa, 259-1193, Japan

Location

Local Institution - 501

Kashiwa, 277-8577, Japan

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Local Institution - 510

Kyoto, 602-8566, Japan

Location

Local Institution - 506

Minami-Ku, Fukuoka, 811-1347, Japan

Location

Local Institution - 507

Nagoya, 464-8681, Japan

Location

Local Institution - 515

Sendai, 983-8520, Japan

Location

Local Institution - 504

Yamagata, 990-9585, Japan

Location

Local Institution - 353

's-Hertogenbosch, 5223 GZ, Netherlands

Location

Local Institution - 358

Amsterdam, 1081 HV, Netherlands

Location

Local Institution - 359

Breda, 4818 CK, Netherlands

Location

Local Institution - 357

Hoofddorp, 2135, Netherlands

Location

Local Institution - 354

Leeuwarden, 8934 AD, Netherlands

Location

Local Institution - 350

Schiedam, 3118 JH, Netherlands

Location

Local Institution - 240

Christchurch, 8011, New Zealand

Location

Local Institution - 243

Palmerston, 4414, New Zealand

Location

Local Institution - 730

Figueira da Foz Municipality, 3094-001, Portugal

Location

Local Institution - 732

Lisbon, 1099-023, Portugal

Location

Local Institution - 729

Lisbon, 1400-038, Portugal

Location

Local Institution - 727

Pragal, 2801-951, Portugal

Location

Local Institution - 115

San Juan, 00918, Puerto Rico

Location

Local Institution - 050

Kazan', 420029, Russia

Location

Local Institution - 052

Moscow, 115478, Russia

Location

Local Institution - 051

Saint Petersburg, 197758, Russia

Location

Local Institution - 830

Gyeonggi-do, 410-769, South Korea

Location

Local Institution - 826

Seoul, 06591, South Korea

Location

Local Institution - 829

Seoul, 135-710, South Korea

Location

Local Institution - 828

Seoul, 138-736, South Korea

Location

Local Institution - 776

Barcelona, 08025, Spain

Location

Local Institution - 780

Barcelona, 08916, Spain

Location

Local Institution - 796

Cáceres, 10003, Spain

Location

Local Institution - 783

Madrid, 28007, Spain

Location

Local Institution - 785

Madrid, 28034, Spain

Location

Local Institution - 787

Madrid, 28040, Spain

Location

Local Institution - 788

Madrid, 28050, Spain

Location

Local Institution - 797

Salamanca, 37007, Spain

Location

Local Institution - 790

Seville, 41013, Spain

Location

Local Institution - 800

Seville, 41014, Spain

Location

Local Institution - 793

Valencia, 46010, Spain

Location

Local Institution - 802

Valencia, 46026, Spain

Location

Local Institution - 323

Bellinzona, 6500, Switzerland

Location

Local Institution - 320

Geneva, 1211, Switzerland

Location

Local Institution - 321

Winterthur, 8400, Switzerland

Location

Local Institution - 253

Niao-Sung Hsiang Kaohsiung County, 83301, Taiwan

Location

Local Institution - 255

Taichung, 40447, Taiwan

Location

Local Institution - 252

Taipei, Zhongzheng Dist., 10002, Taiwan

Location

Local Institution - 429

Adana, 01330, Turkey (Türkiye)

Location

Local Institution - 431

Ankara, 06590, Turkey (Türkiye)

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Local Institution - 430

Antalya, 07058, Turkey (Türkiye)

Location

Local Institution - 435

Denizli, 20070, Turkey (Türkiye)

Location

Local Institution - 428

Edirne, 22030, Turkey (Türkiye)

Location

Local Institution - 432

Istanbul, 34093, Turkey (Türkiye)

Location

Related Publications (3)

• 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.

  PMID: 27089170 BACKGROUND

• 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.

  PMID: 39563886 DERIVED

• 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.

  PMID: 33621109 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Limb-girdle muscular dystrophy, type 2C

Interventions

Lenalidomide; Rituximab; Cyclophosphamide; Doxorubicin; Prednisone; Vincristine

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2014
• First Posted: November 6, 2014
• Study Start: February 17, 2015
• Primary Completion: March 15, 2019
• Study Completion: July 28, 2022
• Last Updated: June 22, 2023
• Results First Posted: March 30, 2020

Record last verified: 2023-05

Locations

PR (1); TW (3); CZ (5); AU (4); FR (7); BE (4); US (22); IL (7); NL (6); PT (4); IT (29); NZ (2); IE (2); JP (12); ES (12); RU (3); CA (5); CN (17); TU (6); KR (4); CH (3)