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

NCT ID: NCT01996865

Last Updated: 2025-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 503 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-01
• Study Completion Date: 2024-09-17

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.

Detailed Description

MAGNIFY (NCT01996865) is a phase 3b, multicenter, open-label study of patients with grades 1-3b or transformed follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL) who received ≥1 prior therapy and had stage I-IV, measurable disease. ~500 patients are planned for enrollment in 12 cycles of R2 induction, with a projected ~314 patients with ≥SD after induction randomized (1:1) to two maintenance arms. Induction includes oral lenalidomide 20 mg/day, days 1-21 per 28-day cycle (d1-21/28) plus IV rituximab 375 mg/m2, days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 3, 5, 7, 9, and 11 (28-day cycles). Patients are then randomized to maintenance lenalidomide 10 mg/day, d1-21/28, cycles 13-30, plus rituximab 375 mg/m2, day 1 of cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29 (R2, Arm A), or rituximab alone (same schedule, Arm B). Patients receiving R2 maintenance after 18 cycles may continue maintenance lenalidomide monotherapy 10 mg/day, d1-21/28 (per patient and/or investigator discretion), until disease progression as tolerated. The primary endpoint is progression-free survival (per modified 1999 IWG criteria). Secondary endpoints include safety, overall survival, response rates, duration of response, and quality of life (exploratory). Patients will be followed for ≥5 years after the last patient initiated induction therapy. Enrollment in MAGNIFY began in March 2014; as of Jan 2016, 133 patients are enrolled.

Conditions

Lymphoma, Non-Hodgkin

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: Lenalidomide + rituximab followed by lenalidomide

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

Group Type: EXPERIMENTAL

Lenalidomide

Intervention Type: DRUG

Rituximab

Intervention Type: DRUG

Arm B: Lenalidomide + rituximab followed by rituximab

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

Group Type: ACTIVE_COMPARATOR

Lenalidomide

Intervention Type: DRUG

Rituximab

Intervention Type: DRUG

Interventions

Lenalidomide

Intervention Type: DRUG

Rituximab

Intervention Type: DRUG

Other Intervention Names

CC-5013, Revlimid; Rituxan

Eligibility Criteria

Inclusion Criteria

-- 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Local Institution - 055

Tucson, Arizona, United States

Local Institution - 077

Little Rock, Arkansas, United States

Local Institution - 079

Berkeley, California, United States

Local Institution - 142

Concord, California, United States

Bay Area Cancer Research Group, LLC

Pleasant Hill, California, United States

Sutter Hematology and Oncology

Sacramento, California, United States

Local Institution - 032

San Diego, California, United States

Local Institution - 130

Santa Barbara, California, United States

Local Institution - 052

Boulder, Colorado, United States

Local Institution - 106

Denver, Colorado, United States

Colorado Cancer Research Program

Denver, Colorado, United States

Local Institution - 062

Glenwood Springs, Colorado, United States

Praxair Cancer Center Danbury

Danbury, Connecticut, United States

Medical Oncology and Blood Disorders, LLP

Manchester, Connecticut, United States

Local Institution - 041

Norwalk, Connecticut, United States

Hematology Oncology Associates, PC

Stamford, Connecticut, United States

Local Institution - 149

Trumbull, Connecticut, United States

Local Institution - 116

Waterbury, Connecticut, United States

Local Institution - 068

Fleming Island, Florida, United States

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, United States

Local Institution - 054

Ocala, Florida, United States

Local Institution - 114

Pensacola, Florida, United States

Local Institution - 011

Marietta, Georgia, United States

Local Institution - 083

Newnan, Georgia, United States

Local Institution - 108

Elk Grove Village, Illinois, United States

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

Hines, Illinois, United States

Local Institution - 159

Hinsdale, Illinois, United States

Local Institution - 056

Niles, Illinois, United States

Local Institution - 028

Park Ridge, Illinois, United States

Orchard Healthcare Research Inc.

Skokie, Illinois, United States

American Health Network of Indiana, LLC

New Albany, Indiana, United States

McFarland Clinic

Ames, Iowa, United States

Siouxland Hematology-Oncology Associates, LLP

Sioux City, Iowa, United States

Cedar Valley Medical Specialists

Waterloo, Iowa, United States

Local Institution - 019

Fairway, Kansas, United States

Local Institution - 350

Great Bend, Kansas, United States

Kentucky Cancer Clinic

Hazard, Kentucky, United States

Local Institution - 138

Louisville, Kentucky, United States

Local Institution - 143

Waterville, Maine, United States

Anne Arundel Medical Center

Annapolis, Maryland, United States

Local Institution - 030

Baltimore, Maryland, United States

Associates Of Oncology/Hematology, P.C.

Rockville, Maryland, United States

Local Institution - 051

Ann Arbor, Michigan, United States

Local Institution - 033

Lansing, Michigan, United States

Local Institution - 164

Rochester, Minnesota, United States

Local Institution - 050

Bolivar, Missouri, United States

Local Institution - 103

Columbia, Missouri, United States

Local Institution - 013

Springfield, Missouri, United States

Local Institution - 042

St Louis, Missouri, United States

Local Institution - 003

Lincoln, Nebraska, United States

Local Institution - 098

Lebanon, New Hampshire, United States

Summit Medical Group Overlook Oncology Center

Berkeley Heights, New Jersey, United States

Veterans Affairs New Jersey Health Care System

East Orange, New Jersey, United States

Local Institution - 080

Englewood, New Jersey, United States

Local Institution - 025

Mount Holly, New Jersey, United States

Saint Peter'S University Hospital

New Brunswick, New Jersey, United States

Brookdale University Hospital and Medical Center

Brooklyn, New York, United States

C.R. Wood Cancer Center at Glens Falls Hospital

Glens Falls, New York, United States

Broome Oncology, LLC

Johnson City, New York, United States

Local Institution - 152

Lake Success, New York, United States

Local Institution - 023

Kinston, North Carolina, United States

Local Institution - 039

Raleigh, North Carolina, United States

Summa Health System Akron City Hospital Laboratory

Akron, Ohio, United States

Aultman Hospital

Canton, Ohio, United States

Local Institution - 161

Cincinnati, Ohio, United States

Local Institution - 047

Cleveland, Ohio, United States

Local Institution - 045

Columbus, Ohio, United States

Toledo Clinic Cancer Center

Toledo, Ohio, United States

Local Institution - 037

Oklahoma City, Oklahoma, United States

Local Institution - 059

Eugene, Oregon, United States

Hematology Oncology Associates, P.C.

Medford, Oregon, United States

Local Institution - 073

Greenville, South Carolina, United States

Spartanburg Regional Healthcare System - Gibbs Cancer Center & Research Institute

Spartanburg, South Carolina, United States

Rapid City Regional Hospital

Rapid City, South Dakota, United States

Local Institution - 153

Sioux Falls, South Dakota, United States

Baptist Cancer Center

Memphis, Tennessee, United States

Local Institution - 076

Memphis, Tennessee, United States

Local Institution - 166

Amarillo, Texas, United States

Arlington Cancer Center

Arlington, Texas, United States

Texas Oncology-Arlington South

Arlington, Texas, United States

Local Institution - 105

Dallas, Texas, United States

Local Institution - 026

Houston, Texas, United States

Local Institution - 067

Houston, Texas, United States

Local Institution - 008

Houston, Texas, United States

Local Institution - 021

Plano, Texas, United States

Local Institution - 071

Round Rock, Texas, United States

Local Institution - 070

San Antonio, Texas, United States

Local Institution - 058

San Antonio, Texas, United States

Local Institution - 111

Temple, Texas, United States

Local Institution - 094

Tyler, Texas, United States

Local Institution - 163

Tyler, Texas, United States

Local Institution - 057

Webster, Texas, United States

Local Institution - 090

Salt Lake City, Utah, United States

Rutland Regional Medical Center

Rutland, Vermont, United States

Local Institution - 053

Christiansburg, Virginia, United States

Local Institution - 129

Fort Belvoir, Virginia, United States

Local Institution - 081

Norfolk, Virginia, United States

Cancer Treatment Center of America

Portsmouth, Virginia, United States

PeaceHealth St. Joseph Medical Center

Bellingham, Washington, United States

Local Institution - 049

Gig Harbor, Washington, United States

Local Institution - 119

Olympia, Washington, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

Local Institution - 104

Vancouver, Washington, United States

Local Institution - 099

Walla Walla, Washington, United States

Local Institution - 006

Wenatchee, Washington, United States

Local Institution - 038

Morgantown, West Virginia, United States

Aurora Health Care Aurora Research

Milwaukee, Wisconsin, United States

Local Institution - 301

Mukwonago, Wisconsin, United States

Local Institution - 300

Oconomowoc, Wisconsin, United States

Local Institution - 101

Waukesha, Wisconsin, United States

Local Institution - 208

Berlin, , Germany

Local Institution - 202

Bremen, , Germany

Local Institution - 213

Cologne, , Germany

Local Institution - 205

Frankfurt, , Germany

Local Institution - 211

Frechen, , Germany

Local Institution - 200

Giessen, , Germany

Local Institution - 203

Hanover, , Germany

Local Institution - 206

Kassel, , Germany

Local Institution - 210

Marburg, , Germany

Local Institution - 215

Mönchengladbach, , Germany

Local Institution - 204

München, , Germany

Local Institution - 212

Münster, , Germany

Local Institution - 201

Potsdam, , Germany

Local Institution - 207

Ravensberg, , Germany

Local Institution - 209

Würzburg, , Germany

Local Institution - 029

San Juan, , Puerto Rico

Countries

United States; Germany; Puerto Rico

References

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.

Reference Type: BACKGROUND

PMID: 30897038 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30919940 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

BMS Clinical Trial Information

http://www.BMSClinicalTrials.com

BMS Clinical Trial Patient Recruiting

Other Identifiers

CC-5013-NHL-008

Identifier Type: -

Identifier Source: org_study_id