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

Lymphoma, Non-Hodgkin Clinical Trial

— MAGNIFY  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01996865
• Other study ID #: CC-5013-NHL-008
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 1, 2014
• Est. completion date: July 8, 2024

Study information

• Verified date: May 2024
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 503
• Est. completion date: July 8, 2024
• Est. primary completion date: May 9, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• Lenalidomide

• Rituximab

Locations

Country	Name	City	State
Germany	Local Institution - 208	Berlin
Germany	Local Institution - 202	Bremen
Germany	Local Institution - 205	Frankfurt
Germany	Local Institution - 211	Frechen
Germany	Local Institution - 200	Gießen
Germany	Local Institution - 203	Hannover
Germany	Local Institution - 206	Kassel
Germany	Local Institution - 213	Köln
Germany	Local Institution - 210	Marburg
Germany	Local Institution - 215	Mönchengladbach
Germany	Local Institution - 204	Munchen
Germany	Local Institution - 212	Münster
Germany	Local Institution - 201	Potsdam
Germany	Local Institution - 207	Ravensberg
Germany	Local Institution - 209	Würzburg
Puerto Rico	Local Institution - 029	San Juan
United States	Summa Health System Akron City Hospital Laboratory	Akron	Ohio
United States	Texas Oncology, P.A.- Amarillo	Amarillo	Texas
United States	McFarland Clinic	Ames	Iowa
United States	Local Institution - 051	Ann Arbor	Michigan
United States	Anne Arundel Medical Center	Annapolis	Maryland
United States	Arlington Cancer Center	Arlington	Texas
United States	Texas Oncology-Arlington South	Arlington	Texas
United States	Local Institution - 030	Baltimore	Maryland
United States	PeaceHealth St. Joseph Medical Center	Bellingham	Washington
United States	Local Institution - 079	Berkeley	California
United States	Summit Medical Group Overlook Oncology Center	Berkeley Heights	New Jersey
United States	Local Institution - 050	Bolivar	Missouri
United States	Local Institution - 052	Boulder	Colorado
United States	Brookdale University Hospital and Medical Center	Brooklyn	New York
United States	Aultman Hospital	Canton	Ohio
United States	Local Institution - 053	Christiansburg	Virginia
United States	Local Institution - 161	Cincinnati	Ohio
United States	Local Institution - 047	Cleveland	Ohio
United States	Local Institution - 103	Columbia	Missouri
United States	Local Institution - 045	Columbus	Ohio
United States	John Muir Health	Concord	California
United States	Local Institution - 105	Dallas	Texas
United States	Praxair Cancer Center Danbury	Danbury	Connecticut
United States	Colorado Cancer Research Program	Denver	Colorado
United States	Local Institution - 106	Denver	Colorado
United States	Veterans Affairs New Jersey Health Care System	East Orange	New Jersey
United States	Local Institution - 108	Elk Grove Village	Illinois
United States	Local Institution - 080	Englewood	New Jersey
United States	Local Institution - 059	Eugene	Oregon
United States	Local Institution - 019	Fairway	Kansas
United States	Cancer Specialists, LLC dba Cancer Specialists of North Florida	Fleming Island	Florida
United States	Fort Belvoir Community Hospital	Fort Belvoir	Virginia
United States	Local Institution - 049	Gig Harbor	Washington
United States	C.R. Wood Cancer Center at Glens Falls Hospital	Glens Falls	New York
United States	Local Institution - 062	Glenwood Springs	Colorado
United States	Local Institution - 350	Great Bend	Kansas
United States	Local Institution - 073	Greenville	South Carolina
United States	Kentucky Cancer Clinic	Hazard	Kentucky
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 - 008	Houston	Texas
United States	Local Institution - 026	Houston	Texas
United States	Local Institution - 067	Houston	Texas
United States	Broome Oncology, LLC	Johnson City	New York
United States	Local Institution - 023	Kinston	North Carolina
United States	Local Institution - 152	Lake Success	New York
United States	Local Institution - 033	Lansing	Michigan
United States	Local Institution - 098	Lebanon	New Hampshire
United States	Local Institution - 003	Lincoln	Nebraska
United States	Local Institution - 077	Little Rock	Arkansas
United States	Local Institution - 138	Louisville	Kentucky
United States	Medical Oncology and Blood Disorders, LLP	Manchester	Connecticut
United States	Local Institution - 011	Marietta	Georgia
United States	Hematology Oncology Associates, P.C.	Medford	Oregon
United States	Baptist Cancer Center	Memphis	Tennessee
United States	Local Institution - 076	Memphis	Tennessee
United States	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	Aurora Health Care Aurora Research	Milwaukee	Wisconsin
United States	Local Institution - 038	Morgantown	West Virginia
United States	Regional Cancer Care Associates LLC	Mount Holly	New Jersey
United States	Local Institution - 301	Mukwonago	Wisconsin
United States	American Health Network of Indiana, LLC	New Albany	Indiana
United States	Saint Peter'S University Hospital	New Brunswick	New Jersey
United States	Local Institution - 083	Newnan	Georgia
United States	Local Institution - 056	Niles	Illinois
United States	Local Institution - 081	Norfolk	Virginia
United States	Local Institution - 041	Norwalk	Connecticut
United States	Local Institution - 054	Ocala	Florida
United States	Local Institution - 300	Oconomowoc	Wisconsin
United States	Local Institution - 037	Oklahoma City	Oklahoma
United States	Local Institution - 119	Olympia	Washington
United States	Local Institution - 028	Park Ridge	Illinois
United States	Sacred Heart Medical Oncology Group	Pensacola	Florida
United States	Texas Health Physicians Group	Plano	Texas
United States	Bay Area Cancer Research Group, LLC	Pleasant Hill	California
United States	Cancer Treatment Center of America	Portsmouth	Virginia
United States	Local Institution - 039	Raleigh	North Carolina
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Local Institution - 164	Rochester	Minnesota
United States	Associates Of Oncology/Hematology, P.C.	Rockville	Maryland
United States	Local Institution - 071	Round Rock	Texas
United States	Rutland Regional Medical Center	Rutland	Vermont
United States	Sutter Hematology and Oncology	Sacramento	California
United States	Local Institution - 042	Saint Louis	Missouri
United States	Local Institution - 090	Salt Lake City	Utah
United States	Local Institution - 058	San Antonio	Texas
United States	Local Institution - 070	San Antonio	Texas
United States	Local Institution - 032	San Diego	California
United States	Local Institution - 130	Santa Barbara	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	Local Institution - 153	Sioux Falls	South Dakota
United States	Orchard Healthcare Research Inc.	Skokie	Illinois
United States	Spartanburg Regional Healthcare System - Gibbs Cancer Center & Research Institute	Spartanburg	South Carolina
United States	Mercy Medical Research Institute	Springfield	Missouri
United States	Hematology Oncology Associates, PC	Stamford	Connecticut
United States	Local Institution - 111	Temple	Texas
United States	Toledo Clinic Cancer Center	Toledo	Ohio
United States	Local Institution - 149	Trumbull	Connecticut
United States	Local Institution - 055	Tucson	Arizona
United States	Local Institution - 163	Tyler	Texas
United States	Tyler Hematology and Oncology	Tyler	Texas
United States	Local Institution - 104	Vancouver	Washington
United States	Local Institution - 099	Walla Walla	Washington
United States	Local Institution - 116	Waterbury	Connecticut
United States	Cedar Valley Medical Specialists	Waterloo	Iowa
United States	Maine General Medical Center	Waterville	Maine
United States	Local Institution - 101	Waukesha	Wisconsin
United States	Texas Oncology, P.A. - Deke Slayton Cancer Center	Webster	Texas
United States	Local Institution - 006	Wenatchee	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Germany,  Puerto Rico, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival (PFS) for Follicular lymphoma (FL), marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL)	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	Up to 8 years
Secondary	Overall Survival	Overall Survival is defined as the time between the first dose date of maintenance therapy and death from any cause	10 years
Secondary	Improvement of Response	Improvement of response is defined as the proportion of participants who have improved their tumor response during the maintenance phase	8 years
Secondary	Overall response rate	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).	8 years
Secondary	Complete response rate	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)	8 years
Secondary	Duration of response	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	8 years
Secondary	Duration of complete response	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	8 years
Secondary	Time to next anti-lymphoma treatment	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	8 years
Secondary	Time to histological transformation	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	8 years
Secondary	Adverse Events	Number of participants with adverse events	Up to 10 years

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting