Clinical trial NCT01996865: Lenalidomide Plus Rituximab Followed by Lenalidomide Versus Rituximab Maintenance for Relapsed/Refractory Follicular, Marginal Zone or Mantle Cell Lymphoma.
Official title: A Phase 3B Randomized Study of Lenalidomide (CC-5013) Plus Rituximab Maintenance Therapy Followed by Lenalidomide Single-Agent Maintenance Versus Rituximab Maintenance in Subjects With Relapsed/Refractory Follicular, Marginal Zone, or Mantle Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lymphoma, Non-Hodgkin
Keywords: Lymphoma, Mantle cell Lymphoma, Follicular Lymphoma, Marginal zone Lymphoma, Lenalidomide treatment, rituximab treatment, Non Hodgkins Lymphoma
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2013-11-27
Enrollment: 503
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Other protocol-defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Progression free survival (PFS) for Follicular lymphoma (FL), marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL)
timeFrame: Up to 8 years
Secondary outcomes:
measure: Overall Survival
timeFrame: 10 years
measure: Improvement of Response
timeFrame: 8 years
measure: Overall response rate
timeFrame: 8 years
measure: Complete response rate
timeFrame: 8 years
measure: Duration of response
timeFrame: 8 years
measure: Duration of complete response
timeFrame: 8 years
measure: Time to next anti-lymphoma treatment
timeFrame: 8 years
measure: Time to histological transformation
timeFrame: 8 years
measure: Adverse Events
timeFrame: Up to 10 years
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Local Institution - 055
state: Arizona
city: Little Rock
country: United States
facility: Local Institution - 077
state: Arkansas
city: Berkeley
country: United States
facility: Local Institution - 079
state: California
city: Concord
country: United States
facility: Local Institution - 142
state: California
city: Pleasant Hill
country: United States
facility: Bay Area Cancer Research Group, LLC
state: California
city: Sacramento
country: United States
facility: Sutter Hematology and Oncology
state: California
city: San Diego
country: United States
facility: Local Institution - 032
state: California
city: Santa Barbara
country: United States
facility: Local Institution - 130
state: California
city: Boulder
country: United States
facility: Local Institution - 052
state: Colorado
city: Denver
country: United States
facility: Local Institution - 106
state: Colorado
city: Denver
country: United States
facility: Colorado Cancer Research Program
state: Colorado
city: Glenwood Springs
country: United States
facility: Local Institution - 062
state: Colorado
city: Danbury
country: United States
facility: Praxair Cancer Center Danbury
state: Connecticut
city: Manchester
country: United States
facility: Medical Oncology and Blood Disorders, LLP
state: Connecticut
city: Norwalk
country: United States
facility: Local Institution - 041
state: Connecticut
city: Stamford
country: United States
facility: Hematology Oncology Associates, PC
state: Connecticut
city: Trumbull
country: United States
facility: Local Institution - 149
state: Connecticut
city: Waterbury
country: United States
facility: Local Institution - 116
state: Connecticut
city: Fleming Island
country: United States
facility: Local Institution - 068
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Comprehensive Cancer Center
state: Florida
city: Ocala
country: United States
facility: Local Institution - 054
state: Florida
city: Pensacola
country: United States
facility: Local Institution - 114
state: Florida
city: Marietta
country: United States
facility: Local Institution - 011
state: Georgia
city: Newnan
country: United States
facility: Local Institution - 083
state: Georgia
city: Elk Grove Village
country: United States
facility: Local Institution - 108
state: Illinois
city: Hines
country: United States
facility: United States Department of Veterans Affairs - VA Great Lakes Health Care System - Edward Hines Jr
state: Illinois
city: Hinsdale
country: United States
facility: Local Institution - 159
state: Illinois
city: Niles
country: United States
facility: Local Institution - 056
state: Illinois
city: Park Ridge
country: United States
facility: Local Institution - 028
state: Illinois
city: Skokie
country: United States
facility: Orchard Healthcare Research Inc.
state: Illinois
city: New Albany
country: United States
facility: American Health Network of Indiana, LLC
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates, LLP
state: Iowa
city: Waterloo
country: United States
facility: Cedar Valley Medical Specialists
state: Iowa
city: Fairway
country: United States
facility: Local Institution - 019
state: Kansas
city: Great Bend
country: United States
facility: Local Institution - 350
state: Kansas
city: Hazard
country: United States
facility: Kentucky Cancer Clinic
state: Kentucky
city: Louisville
country: United States
facility: Local Institution - 138
state: Kentucky
city: Waterville
country: United States
facility: Local Institution - 143
state: Maine
city: Annapolis
country: United States
facility: Anne Arundel Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Local Institution - 030
state: Maryland
city: Rockville
country: United States
facility: Associates Of Oncology/Hematology, P.C.
state: Maryland
city: Ann Arbor
country: United States
facility: Local Institution - 051
state: Michigan
city: Lansing
country: United States
facility: Local Institution - 033
state: Michigan
city: Rochester
country: United States
facility: Local Institution - 164
state: Minnesota
city: Bolivar
country: United States
facility: Local Institution - 050
state: Missouri
city: Columbia
country: United States
facility: Local Institution - 103
state: Missouri
city: Saint Louis
country: United States
facility: Local Institution - 042
state: Missouri
city: Springfield
country: United States
facility: Local Institution - 013
state: Missouri
city: Lincoln
country: United States
facility: Local Institution - 003
state: Nebraska
city: Lebanon
country: United States
facility: Local Institution - 098
state: New Hampshire
city: Berkeley Heights
country: United States
facility: Summit Medical Group Overlook Oncology Center
state: New Jersey
city: East Orange
country: United States
facility: Veterans Affairs New Jersey Health Care System
state: New Jersey
city: Englewood
country: United States
facility: Local Institution - 080
state: New Jersey
city: Mount Holly
country: United States
facility: Local Institution - 025
state: New Jersey
city: New Brunswick
country: United States
facility: Saint Peter'S University Hospital
state: New Jersey
city: Brooklyn
country: United States
facility: Brookdale University Hospital and Medical Center
state: New York
city: Glens Falls
country: United States
facility: C.R. Wood Cancer Center at Glens Falls Hospital
state: New York
city: Johnson City
country: United States
facility: Broome Oncology, LLC
state: New York
city: Lake Success
country: United States
facility: Local Institution - 152
state: New York
city: Kinston
country: United States
facility: Local Institution - 023
state: North Carolina
city: Raleigh
country: United States
facility: Local Institution - 039
state: North Carolina
city: Akron
country: United States
facility: Summa Health System Akron City Hospital Laboratory
state: Ohio
city: Canton
country: United States
facility: Aultman Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Local Institution - 161
state: Ohio
city: Cleveland
country: United States
facility: Local Institution - 047
state: Ohio
city: Columbus
country: United States
facility: Local Institution - 045
state: Ohio
city: Toledo
country: United States
facility: Toledo Clinic Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: Local Institution - 037
state: Oklahoma
city: Eugene
country: United States
facility: Local Institution - 059
state: Oregon
city: Medford
country: United States
facility: Hematology Oncology Associates, P.C.
state: Oregon
city: Greenville
country: United States
facility: Local Institution - 073
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Regional Healthcare System - Gibbs Cancer Center & Research Institute
state: South Carolina
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Sioux Falls
country: United States
facility: Local Institution - 153
state: South Dakota
city: Memphis
country: United States
facility: Baptist Cancer Center
state: Tennessee
city: Memphis
country: United States
facility: Local Institution - 076
state: Tennessee
city: Amarillo
country: United States
facility: Local Institution - 166
state: Texas
city: Arlington
country: United States
facility: Arlington Cancer Center
state: Texas
city: Arlington
country: United States
facility: Texas Oncology-Arlington South
state: Texas
city: Dallas
country: United States
facility: Local Institution - 105
state: Texas
city: Houston
country: United States
facility: Local Institution - 026
state: Texas
city: Houston
country: United States
facility: Local Institution - 067
state: Texas
city: Houston
country: United States
facility: Local Institution - 008
state: Texas
city: Plano
country: United States
facility: Local Institution - 021
state: Texas
city: Round Rock
country: United States
facility: Local Institution - 071
state: Texas
city: San Antonio
country: United States
facility: Local Institution - 070
state: Texas
city: San Antonio
country: United States
facility: Local Institution - 058
state: Texas
city: Temple
country: United States
facility: Local Institution - 111
state: Texas
city: Tyler
country: United States
facility: Local Institution - 094
state: Texas
city: Tyler
country: United States
facility: Local Institution - 163
state: Texas
city: Webster
country: United States
facility: Local Institution - 057
state: Texas
city: Salt Lake City
country: United States
facility: Local Institution - 090
state: Utah
city: Rutland
country: United States
facility: Rutland Regional Medical Center
state: Vermont
city: Christiansburg
country: United States
facility: Local Institution - 053
state: Virginia
city: Fort Belvoir
country: United States
facility: Local Institution - 129
state: Virginia
city: Norfolk
country: United States
facility: Local Institution - 081
state: Virginia
city: Portsmouth
country: United States
facility: Cancer Treatment Center of America
state: Virginia
city: Bellingham
country: United States
facility: PeaceHealth St. Joseph Medical Center
state: Washington
city: Gig Harbor
country: United States
facility: Local Institution - 049
state: Washington
city: Olympia
country: United States
facility: Local Institution - 119
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Vancouver
country: United States
facility: Local Institution - 104
state: Washington
city: Walla Walla
country: United States
facility: Local Institution - 099
state: Washington
city: Wenatchee
country: United States
facility: Local Institution - 006
state: Washington
city: Morgantown
country: United States
facility: Local Institution - 038
state: West Virginia
city: Milwaukee
country: United States
facility: Aurora Health Care Aurora Research
state: Wisconsin
city: Mukwonago
country: United States
facility: Local Institution - 301
state: Wisconsin
city: Oconomowoc
country: United States
facility: Local Institution - 300
state: Wisconsin
city: Waukesha
country: United States
facility: Local Institution - 101
state: Wisconsin
city: Berlin
country: Germany
facility: Local Institution - 208
city: Bremen
country: Germany
facility: Local Institution - 202
city: Frankfurt
country: Germany
facility: Local Institution - 205
city: Frechen
country: Germany
facility: Local Institution - 211
city: Gießen
country: Germany
facility: Local Institution - 200
city: Hannover
country: Germany
facility: Local Institution - 203
city: Kassel
country: Germany
facility: Local Institution - 206
city: Köln
country: Germany
facility: Local Institution - 213
city: Marburg
country: Germany
facility: Local Institution - 210
city: Munchen
country: Germany
facility: Local Institution - 204
city: Mönchengladbach
country: Germany
facility: Local Institution - 215
city: Münster
country: Germany
facility: Local Institution - 212
city: Potsdam
country: Germany
facility: Local Institution - 201
city: Ravensberg
country: Germany
facility: Local Institution - 207
city: Würzburg
country: Germany
facility: Local Institution - 209
city: San Juan
country: Puerto Rico
facility: Local Institution - 029
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.