Lenalidomide Plus Rituximab Followed by Lenalidomide Versus Rituximab Maintenance for Relapsed/Refractory Follicular, Marginal Zone or Mantle Cell Lymphoma.
- Registration Number
- NCT01996865
- Lead Sponsor
- Celgene
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 503
-- 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
- 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
Other protocol-defined inclusion/exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Lenalidomide + rituximab followed by lenalidomide 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 Arm A: Lenalidomide + rituximab followed by lenalidomide Rituximab 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 Arm B: Lenalidomide + rituximab followed by rituximab Lenalidomide 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 Arm B: Lenalidomide + rituximab followed by rituximab 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
- Primary Outcome Measures
Name Time Method Progression free survival (PFS) for Follicular lymphoma (FL), marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL) Up to 8 years Progression free survival is defined as the time from the first dose date of maintenance therapy to objective disease progression or death from any cause
- Secondary Outcome Measures
Name Time Method Improvement of Response 8 years Improvement of response is defined as the proportion of participants who have improved their tumor response during the maintenance phase
Overall response rate 8 years Overall response rate is defined as proportion of subjects with a best response of at least partial remission (including partial remission, complete remission and unconfirmed complete remission).
Complete response rate 8 years Complete response rate is defined as proportion of subjects with a best response of at least unconfirmed complete remission (including complete remission and unconfirmed complete remission)
Time to next anti-lymphoma treatment 8 years Time to next anti-lymphoma treatment is defined as the time from the first dose date of maintenance therapy to the time of first documented administration of new anti-lymphoma therapy
Time to histological transformation 8 years Time to histological transformation is defined as the time from the first dose date of maintenance therapy to the time of histological transformation as measured based on documentation of histological transformation
Overall Survival 10 years Overall Survival is defined as the time between the first dose date of maintenance therapy and death from any cause
Duration of complete response 8 years Duration of complete response is defined as the time from the initial response (at least CRu) after the first dose date of maintenance therapy and prior to treatment change to documented disease progression or death
Duration of response 8 years Duration of response is defined as the time from the initial response (at least partial remission) after the first dose date of maintenance therapy and prior to treatment change to documented disease progression or death
Adverse Events Up to 10 years Number of participants with adverse events
Trial Locations
- Locations (126)
Local Institution - 011
🇺🇸Marietta, Georgia, United States
Local Institution - 056
🇺🇸Niles, Illinois, United States
Local Institution - 028
🇺🇸Park Ridge, Illinois, United States
American Health Network of Indiana, LLC
🇺🇸New Albany, Indiana, United States
Local Institution - 050
🇺🇸Bolivar, Missouri, United States
Local Institution - 032
🇺🇸San Diego, California, United States
Local Institution - 058
🇺🇸San Antonio, Texas, United States
Rapid City Regional Hospital
🇺🇸Rapid City, South Dakota, United States
Local Institution - 153
🇺🇸Sioux Falls, South Dakota, United States
Local Institution - 067
🇺🇸Houston, Texas, United States
Local Institution - 052
🇺🇸Boulder, Colorado, United States
Local Institution - 019
🇺🇸Fairway, Kansas, United States
Local Institution - 049
🇺🇸Gig Harbor, Washington, United States
Local Institution - 101
🇺🇸Waukesha, Wisconsin, United States
Hematology Oncology Associates, PC
🇺🇸Stamford, Connecticut, United States
Local Institution - 055
🇺🇸Tucson, Arizona, United States
Local Institution - 054
🇺🇸Ocala, Florida, United States
Local Institution - 003
🇺🇸Lincoln, Nebraska, United States
Local Institution - 041
🇺🇸Norwalk, Connecticut, United States
Local Institution - 038
🇺🇸Morgantown, West Virginia, United States
Local Institution - 033
🇺🇸Lansing, Michigan, United States
Praxair Cancer Center Danbury
🇺🇸Danbury, Connecticut, United States
Baptist Cancer Center
🇺🇸Memphis, Tennessee, United States
Local Institution - 114
🇺🇸Pensacola, Florida, United States
Summit Medical Group Overlook Oncology Center
🇺🇸Berkeley Heights, New Jersey, United States
Local Institution - 116
🇺🇸Waterbury, Connecticut, United States
Local Institution - 149
🇺🇸Trumbull, Connecticut, United States
Local Institution - 208
🇩🇪Berlin, Germany
Mount Sinai Comprehensive Cancer Center
🇺🇸Miami Beach, Florida, United States
Local Institution - 202
🇩🇪Bremen, Germany
Local Institution - 030
🇺🇸Baltimore, Maryland, United States
Local Institution - 211
🇩🇪Frechen, Germany
Local Institution - 204
🇩🇪Munchen, Germany
Local Institution - 212
🇩🇪Münster, Germany
Spartanburg Regional Healthcare System - Gibbs Cancer Center & Research Institute
🇺🇸Spartanburg, South Carolina, United States
Medical Oncology and Blood Disorders, LLP
🇺🇸Manchester, Connecticut, United States
Hematology Oncology Associates, P.C.
🇺🇸Medford, Oregon, United States
Local Institution - 080
🇺🇸Englewood, New Jersey, United States
Local Institution - 068
🇺🇸Fleming Island, Florida, United States
Local Institution - 143
🇺🇸Waterville, Maine, United States
Local Institution - 200
🇩🇪Gießen, Germany
Saint Peter'S University Hospital
🇺🇸New Brunswick, New Jersey, United States
Veterans Affairs New Jersey Health Care System
🇺🇸East Orange, New Jersey, United States
Local Institution - 300
🇺🇸Oconomowoc, Wisconsin, United States
Local Institution - 203
🇩🇪Hannover, Germany
Local Institution - 090
🇺🇸Salt Lake City, Utah, United States
Associates Of Oncology/Hematology, P.C.
🇺🇸Rockville, Maryland, United States
Anne Arundel Medical Center
🇺🇸Annapolis, Maryland, United States
Local Institution - 301
🇺🇸Mukwonago, Wisconsin, United States
Local Institution - 205
🇩🇪Frankfurt, Germany
Local Institution - 213
🇩🇪Köln, Germany
Local Institution - 201
🇩🇪Potsdam, Germany
Local Institution - 098
🇺🇸Lebanon, New Hampshire, United States
Local Institution - 076
🇺🇸Memphis, Tennessee, United States
Local Institution - 073
🇺🇸Greenville, South Carolina, United States
Local Institution - 059
🇺🇸Eugene, Oregon, United States
Local Institution - 206
🇩🇪Kassel, Germany
Local Institution - 215
🇩🇪Mönchengladbach, Germany
Local Institution - 209
🇩🇪Würzburg, Germany
Local Institution - 106
🇺🇸Denver, Colorado, United States
Colorado Cancer Research Program
🇺🇸Denver, Colorado, United States
Local Institution - 164
🇺🇸Rochester, Minnesota, United States
Rutland Regional Medical Center
🇺🇸Rutland, Vermont, United States
Aurora Health Care Aurora Research
🇺🇸Milwaukee, Wisconsin, United States
Local Institution - 142
🇺🇸Concord, California, United States
Local Institution - 062
🇺🇸Glenwood Springs, Colorado, United States
Sutter Hematology and Oncology
🇺🇸Sacramento, California, United States
Local Institution - 051
🇺🇸Ann Arbor, Michigan, United States
Local Institution - 138
🇺🇸Louisville, Kentucky, United States
Local Institution - 079
🇺🇸Berkeley, California, United States
Bay Area Cancer Research Group, LLC
🇺🇸Pleasant Hill, California, United States
Local Institution - 130
🇺🇸Santa Barbara, California, United States
Local Institution - 083
🇺🇸Newnan, Georgia, United States
Local Institution - 108
🇺🇸Elk Grove Village, Illinois, United States
Local Institution - 159
🇺🇸Hinsdale, Illinois, United States
United States Department of Veterans Affairs - VA Great Lakes Health Care System - Edward Hines Jr
🇺🇸Hines, Illinois, United States
Orchard Healthcare Research Inc.
🇺🇸Skokie, Illinois, United States
McFarland Clinic
🇺🇸Ames, Iowa, United States
Cedar Valley Medical Specialists
🇺🇸Waterloo, Iowa, United States
Siouxland Hematology-Oncology Associates, LLP
🇺🇸Sioux City, Iowa, United States
Kentucky Cancer Clinic
🇺🇸Hazard, Kentucky, United States
Local Institution - 350
🇺🇸Great Bend, Kansas, United States
Local Institution - 013
🇺🇸Springfield, Missouri, United States
Local Institution - 042
🇺🇸Saint Louis, Missouri, United States
Local Institution - 103
🇺🇸Columbia, Missouri, 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
Local Institution - 152
🇺🇸Lake Success, New York, United States
Broome Oncology, LLC
🇺🇸Johnson City, New York, United States
Local Institution - 023
🇺🇸Kinston, North Carolina, United States
Summa Health System Akron City Hospital Laboratory
🇺🇸Akron, Ohio, United States
Local Institution - 039
🇺🇸Raleigh, North Carolina, United States
Local Institution - 047
🇺🇸Cleveland, Ohio, United States
Local Institution - 161
🇺🇸Cincinnati, Ohio, United States
Aultman Hospital
🇺🇸Canton, Ohio, United States
Toledo Clinic Cancer Center
🇺🇸Toledo, Ohio, United States
Local Institution - 037
🇺🇸Oklahoma City, Oklahoma, United States
Local Institution - 045
🇺🇸Columbus, Ohio, United States
Arlington Cancer Center
🇺🇸Arlington, Texas, United States
Local Institution - 166
🇺🇸Amarillo, Texas, United States
Texas Oncology-Arlington South
🇺🇸Arlington, Texas, United States
Local Institution - 026
🇺🇸Houston, Texas, United States
Local Institution - 105
🇺🇸Dallas, Texas, United States
Local Institution - 008
🇺🇸Houston, Texas, United States
Local Institution - 071
🇺🇸Round Rock, Texas, United States
Local Institution - 021
🇺🇸Plano, Texas, United States
Local Institution - 070
🇺🇸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 - 129
🇺🇸Fort Belvoir, Virginia, United States
Local Institution - 053
🇺🇸Christiansburg, 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
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Local Institution - 104
🇺🇸Vancouver, Washington, United States
Local Institution - 119
🇺🇸Olympia, Washington, United States
Local Institution - 099
🇺🇸Walla Walla, Washington, United States
Local Institution - 006
🇺🇸Wenatchee, Washington, United States
Local Institution - 210
🇩🇪Marburg, Germany
Local Institution - 207
🇩🇪Ravensberg, Germany
Local Institution - 029
🇵🇷San Juan, Puerto Rico
Local Institution - 077
🇺🇸Little Rock, Arkansas, United States
Local Institution - 025
🇺🇸Mount Holly, New Jersey, United States