Lenalidomide Plus Rituximab Followed by Lenalidomide Versus Rituximab Maintenance for Relapsed/Refractory Follicular, Marginal Zone or Mantle Cell Lymphoma.

NCT01996865 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: CC-5013-NHL-008
• Study Type: interventional
• Target: 503
• Locations: 3 countries
• Sites: 126

Brief Summary

Follicular lymphoma (FL), marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL) are distinct histologic types of B-cell NHL. Lenalidomide is an immunomodulatory agent with direct and immune-mediated mechanisms of action, as well as clinical activity in NHL. Recent studies in frontline and relapsed/refractory NHL show high activity for lenalidomide plus rituximab (R2), supporting further study of this combination.

Conditions

Lymphoma, Non-Hodgkin

Keywords

Lymphoma, Mantle cell Lymphoma, Follicular Lymphoma, Marginal zone Lymphoma, Lenalidomide treatment, rituximab treatment, Non Hodgkins Lymphoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Progression free survival (PFS) is defined as the time from the date of first dose of maintenance therapy to the date of the first objective documentation of tumor progression or death due to any cause. Analysis was based on Kaplan Meier estimates. The PFS events were determined using a modification of the IWG 1999 criteria.

  From the first dose date of maintenance therapy to objective disease progression or death from any cause, whichever occurs first (up to approximately 432 weeks)

Secondary Outcomes (12)

• Overall Survival (OS)

  From the first dose date of maintenance therapy to death from any cause (up to approximately 480 weeks)

• Improvement of Response (IOR)

  From the first dose date of maintenance therapy to death from any cause (up to approximately 432 weeks)

• Overall Response Rate (ORR)

  From the first dose date of maintenance therapy up to CR, CRu, PR, or treatment change (up to approximately 432 weeks)

• Complete Response Rate (CRR)

  From the first dose date of maintenance therapy up to CR or CRu (up to approximately 432 weeks)

• Duration of Response (DOR)

  From the initial response (at least PR) after the first dose date of maintenance therapy and prior to treatment change to documented disease progression or death, whichever occurs first (up to approximately 432 weeks)

Study Arms (2)

Arm A: Lenalidomide + rituximab followed by lenalidomide

EXPERIMENTAL

Induction Period (12 cycles): Lenalidomide 20mg (10 mg if creatinine clearance ≥ 30 mL/min but \< 60mL/min) by mouth (PO) daily (QD) on Days 1 to 21 of every 28-day cycle during cycles 1 through 12 and rituximab 375mg/m\^2 intraveneously (IV) every week in Cycle 1 on Days 1, 8, 15, and 22 and on Day 1 of every 28-day cycle during cycles 3, 5, 7, 9, and 11, followed by a Maintenance Period (lasting 18 Cycles) that includes Lenalidomide 10 mg PO QD on Days 1 to 21 of every 28-day cycle during cycles 13 to 30 and rituximab 375 mg/m\^2 IV on Day 1 of every 28-day cycle during cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29 followed by an optional Maintenance Period (up to Progressive Disease) receiving Lenalidomide 10mg PO QD on Days 1 through 21 of every 28 day cycle until the disease progresses

Drug: Lenalidomide; Drug: Rituximab

Arm B: Lenalidomide + rituximab followed by rituximab

ACTIVE COMPARATOR

Induction Period (12 Cycles): Lenalidomide 20 mg PO QD (10 mg if creatinine clearance ≥ 30 mL/min but \< 60 mL/min) on Days 1 to 21 of every 28-day cycle during cycles 1 to 12 and rituximab 375 mg/m\^2 IV every week in cycle 1 on Days 1, 8, 15, and 22 and on Day 1 of every 28-day cycle during cycles 3, 5, 7, 9, and 11, followed by a Maintenance Period for 18 Cycles that includes: Rituximab 375 mg/m\^2 IV on Day 1 of every 28-day cycle during cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29

Drug: Lenalidomide; Drug: Rituximab

Interventions

Lenalidomide DRUG

Also known as: CC-5013, Revlimid

Arm A: Lenalidomide + rituximab followed by lenalidomide; Arm B: Lenalidomide + rituximab followed by rituximab

Rituximab DRUG

Also known as: Rituxan

Arm A: Lenalidomide + rituximab followed by lenalidomide; Arm B: Lenalidomide + rituximab followed by rituximab

Eligibility Criteria

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

You may qualify if:

• \-- Age ≥18 years
• Histologically confirmed Follicular Lymphoma (FL, Grade 1, 2, 3a, or 3b), Transformed FL, Marginal Zone Lymphoma, or Mantle Cell Lymphoma
• Must have documented relapsed, refractory or Progressive Disease after last treatment with systemic therapy
• Bi-dimensionally measurable disease
• Eastern Cooperative Oncology Group (ECOG) Performance status \< 2
• Adequate bone marrow function
• Willingness to follow pregnancy precautions

You may not qualify if:

• Histology other than follicular or marginal zone lymphoma or clinical evidence of transformation or Grade 3b follicular lymphoma
• Any medical condition (other than the underlying lymphoma) that requires chronic steroid use
• Subjects taking corticosteroids during the last 1 week prior treatment, unless administered at a dose equivalent to \< 20 mg/day of prednisone
• Systemic anti-lymphoma therapy within 28 days or use of antibody agents within 4 weeks use of radioimmunotherapy within 3 months
• Known seropositive for or active viral infection with hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV)
• Known sensitivity or allergy to murine products
• Presence or history of central nervous system involvement by lymphoma. Subjects who are at a risk for a thromboembolic event and are not willing to take prophylaxis for it
• Any condition that places the subject at unacceptable risk if he/she were to participate in the study or that confounds the ability to interpret data from the study

Sponsors & Collaborators

• Celgene: lead

Study Sites (126)

Local Institution - 055

Tucson, Arizona, 85710, United States

Location

Local Institution - 077

Little Rock, Arkansas, 72205, United States

Location

Local Institution - 079

Berkeley, California, 94704, United States

Location

Local Institution - 142

Concord, California, 94520, United States

Location

Bay Area Cancer Research Group, LLC

Pleasant Hill, California, 94523, United States

Location

Sutter Hematology and Oncology

Sacramento, California, 95816, United States

Location

Local Institution - 032

San Diego, California, 92123, United States

Location

Local Institution - 130

Santa Barbara, California, 93105, United States

Location

Local Institution - 052

Boulder, Colorado, 80303, United States

Location

Local Institution - 106

Denver, Colorado, 80220, United States

Location

Colorado Cancer Research Program

Denver, Colorado, 80222, United States

Location

Local Institution - 062

Glenwood Springs, Colorado, 81601, United States

Location

Praxair Cancer Center Danbury

Danbury, Connecticut, 06810, United States

Location

Medical Oncology and Blood Disorders, LLP

Manchester, Connecticut, 06040, United States

Location

Local Institution - 041

Norwalk, Connecticut, 06851, United States

Location

Hematology Oncology Associates, PC

Stamford, Connecticut, 06902, United States

Location

Local Institution - 149

Trumbull, Connecticut, 06611, United States

Location

Local Institution - 116

Waterbury, Connecticut, 067014, United States

Location

Local Institution - 068

Fleming Island, Florida, 32003, United States

Location

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

Location

Local Institution - 054

Ocala, Florida, 34474, United States

Location

Local Institution - 114

Pensacola, Florida, 32504, United States

Location

Local Institution - 011

Marietta, Georgia, 30060, United States

Location

Local Institution - 083

Newnan, Georgia, 30265, United States

Location

Local Institution - 108

Elk Grove Village, Illinois, 60007, United States

Location

United States Department of Veterans Affairs - VA Great Lakes Health Care System - Edward Hines Jr

Hines, Illinois, 60141, United States

Location

Local Institution - 159

Hinsdale, Illinois, 60521, United States

Location

Local Institution - 056

Niles, Illinois, 60714, United States

Location

Local Institution - 028

Park Ridge, Illinois, 60068, United States

Location

Orchard Healthcare Research Inc.

Skokie, Illinois, 60077, United States

Location

American Health Network of Indiana, LLC

New Albany, Indiana, 47150, United States

Location

McFarland Clinic

Ames, Iowa, 50010, United States

Location

Siouxland Hematology-Oncology Associates, LLP

Sioux City, Iowa, 51101-1733, United States

Location

Cedar Valley Medical Specialists

Waterloo, Iowa, 50701, United States

Location

Local Institution - 019

Fairway, Kansas, 66205, United States

Location

Local Institution - 350

Great Bend, Kansas, 67530, United States

Location

Kentucky Cancer Clinic

Hazard, Kentucky, 41701, United States

Location

Local Institution - 138

Louisville, Kentucky, 40207, United States

Location

Local Institution - 143

Waterville, Maine, 04901, United States

Location

Anne Arundel Medical Center

Annapolis, Maryland, 21401, United States

Location

Local Institution - 030

Baltimore, Maryland, 21204, United States

Location

Associates Of Oncology/Hematology, P.C.

Rockville, Maryland, 20850, United States

Location

Local Institution - 051

Ann Arbor, Michigan, 48106, United States

Location

Local Institution - 033

Lansing, Michigan, 48912, United States

Location

Local Institution - 164

Rochester, Minnesota, 55905, United States

Location

Local Institution - 050

Bolivar, Missouri, 65613, United States

Location

Local Institution - 103

Columbia, Missouri, 65212, United States

Location

Local Institution - 013

Springfield, Missouri, 65804, United States

Location

Local Institution - 042

St Louis, Missouri, 63110, United States

Location

Local Institution - 003

Lincoln, Nebraska, 68510, United States

Location

Local Institution - 098

Lebanon, New Hampshire, 03756, United States

Location

Summit Medical Group Overlook Oncology Center

Berkeley Heights, New Jersey, 07922, United States

Location

Veterans Affairs New Jersey Health Care System

East Orange, New Jersey, 07018, United States

Location

Local Institution - 080

Englewood, New Jersey, 07631, United States

Location

Local Institution - 025

Mount Holly, New Jersey, 08060, United States

Location

Saint Peter'S University Hospital

New Brunswick, New Jersey, 08901, United States

Location

Brookdale University Hospital and Medical Center

Brooklyn, New York, 11212, United States

Location

C.R. Wood Cancer Center at Glens Falls Hospital

Glens Falls, New York, 12801, United States

Location

Broome Oncology, LLC

Johnson City, New York, 13790, United States

Location

Local Institution - 152

Lake Success, New York, 11042, United States

Location

Local Institution - 023

Kinston, North Carolina, 28501-1584, United States

Location

Local Institution - 039

Raleigh, North Carolina, 27607, United States

Location

Summa Health System Akron City Hospital Laboratory

Akron, Ohio, 44202, United States

Location

Aultman Hospital

Canton, Ohio, 44710, United States

Location

Local Institution - 161

Cincinnati, Ohio, 45242, United States

Location

Local Institution - 047

Cleveland, Ohio, 44109, United States

Location

Local Institution - 045

Columbus, Ohio, 43219, United States

Location

Toledo Clinic Cancer Center

Toledo, Ohio, 43623, United States

Location

Local Institution - 037

Oklahoma City, Oklahoma, 73104, United States

Location

Local Institution - 059

Eugene, Oregon, 97401, United States

Location

Hematology Oncology Associates, P.C.

Medford, Oregon, 97504, United States

Location

Local Institution - 073

Greenville, South Carolina, 29615, United States

Location

Spartanburg Regional Healthcare System - Gibbs Cancer Center & Research Institute

Spartanburg, South Carolina, 29303, United States

Location

Rapid City Regional Hospital

Rapid City, South Dakota, 57701, United States

Location

Local Institution - 153

Sioux Falls, South Dakota, 57105, United States

Location

Baptist Cancer Center

Memphis, Tennessee, 38104, United States

Location

Local Institution - 076

Memphis, Tennessee, 38104, United States

Location

Local Institution - 166

Amarillo, Texas, 79106, United States

Location

Arlington Cancer Center

Arlington, Texas, 76012, United States

Location

Texas Oncology-Arlington South

Arlington, Texas, 76014, United States

Location

Local Institution - 105

Dallas, Texas, 75230, United States

Location

Local Institution - 026

Houston, Texas, 77030, United States

Location

Local Institution - 067

Houston, Texas, 77030, United States

Location

Local Institution - 008

Houston, Texas, 77090, United States

Location

Local Institution - 021

Plano, Texas, 75093, United States

Location

Local Institution - 071

Round Rock, Texas, 78681, United States

Location

Local Institution - 070

San Antonio, Texas, 78217, United States

Location

Local Institution - 058

San Antonio, Texas, 78240, United States

Location

Local Institution - 111

Temple, Texas, 66205, United States

Location

Local Institution - 094

Tyler, Texas, 75701, United States

Location

Local Institution - 163

Tyler, Texas, 75702, United States

Location

Local Institution - 057

Webster, Texas, 77598-4420, United States

Location

Local Institution - 090

Salt Lake City, Utah, 84106, United States

Location

Rutland Regional Medical Center

Rutland, Vermont, 05701, United States

Location

Local Institution - 053

Christiansburg, Virginia, 24073, United States

Location

Local Institution - 129

Fort Belvoir, Virginia, 22060, United States

Location

Local Institution - 081

Norfolk, Virginia, 23502, United States

Location

Cancer Treatment Center of America

Portsmouth, Virginia, 23704, United States

Location

PeaceHealth St. Joseph Medical Center

Bellingham, Washington, 98225, United States

Location

Local Institution - 049

Gig Harbor, Washington, 98332, United States

Location

Local Institution - 119

Olympia, Washington, 98502, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Local Institution - 104

Vancouver, Washington, 98684, United States

Location

Local Institution - 099

Walla Walla, Washington, 99362, United States

Location

Local Institution - 006

Wenatchee, Washington, 98801, United States

Location

Local Institution - 038

Morgantown, West Virginia, 26506, United States

Location

Aurora Health Care Aurora Research

Milwaukee, Wisconsin, 53233, United States

Location

Local Institution - 301

Mukwonago, Wisconsin, 53145, United States

Location

Local Institution - 300

Oconomowoc, Wisconsin, 53066, United States

Location

Local Institution - 101

Waukesha, Wisconsin, 53188-5099, United States

Location

Local Institution - 208

Berlin, 10707, Germany

Location

Local Institution - 202

Bremen, 28177, Germany

Location

Local Institution - 213

Cologne, 50677, Germany

Location

Local Institution - 205

Frankfurt, 60389, Germany

Location

Local Institution - 211

Frechen, 50226, Germany

Location

Local Institution - 200

Giessen, 35392, Germany

Location

Local Institution - 203

Hanover, 30171, Germany

Location

Local Institution - 206

Kassel, 34119, Germany

Location

Local Institution - 210

Marburg, 35037, Germany

Location

Local Institution - 215

Mönchengladbach, 41063, Germany

Location

Local Institution - 204

München, 81241, Germany

Location

Local Institution - 212

Münster, 48149, Germany

Location

Local Institution - 201

Potsdam, 14467, Germany

Location

Local Institution - 207

Ravensberg, 88212, Germany

Location

Local Institution - 209

Würzburg, 97080, Germany

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Local Institution - 029

San Juan, 00919-1227, Puerto Rico

Location

Related Publications (2)

• Leonard JP, Trneny M, Izutsu K, Fowler NH, Hong X, Zhu J, Zhang H, Offner F, Scheliga A, Nowakowski GS, Pinto A, Re F, Fogliatto LM, Scheinberg P, Flinn IW, Moreira C, Cabecadas J, Liu D, Kalambakas S, Fustier P, Wu C, Gribben JG; AUGMENT Trial Investigators. AUGMENT: A Phase III Study of Lenalidomide Plus Rituximab Versus Placebo Plus Rituximab in Relapsed or Refractory Indolent Lymphoma. J Clin Oncol. 2019 May 10;37(14):1188-1199. doi: 10.1200/JCO.19.00010. Epub 2019 Mar 21.

  PMID: 30897038 BACKGROUND

• Becnel MR, Nastoupil LJ, Samaniego F, Davis RE, You MJ, Green M, Hagemeister FB, Fanale MA, Fayad LE, Westin JR, Wang M, Oki Y, Forbes SG, Feng L, Neelapu SS, Fowler NH. Lenalidomide plus rituximab (R2 ) in previously untreated marginal zone lymphoma: subgroup analysis and long-term follow-up of an open-label phase 2 trial. Br J Haematol. 2019 Jun;185(5):874-882. doi: 10.1111/bjh.15843. Epub 2019 Mar 28.

  PMID: 30919940 BACKGROUND

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Mantle-Cell; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone

Interventions

Lenalidomide; Rituximab

Condition Hierarchy (Ancestors)

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

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

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: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2013
• First Posted: November 27, 2013
• Study Start: April 1, 2014
• Primary Completion: May 11, 2024
• Study Completion: September 17, 2024
• Last Updated: July 10, 2025
• Results First Posted: July 10, 2025

Record last verified: 2025-07

Locations

DE (15); PR (1); US (110)