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

Sponsor

Celgene (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT01996865

Collaborator

(none)

503

Enrollment

115

Locations

Arms

123.2

Anticipated Duration (Months)

4.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Non-Hodgkin	Drug: Lenalidomide Drug: Rituximab	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

503 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 1, 2014

Anticipated Primary Completion Date :

Apr 8, 2023

Anticipated Study Completion Date :

Jul 8, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: Lenalidomide Other Names: CC-5013, Revlimid Drug: Rituximab Other Names: Rituxan
Active Comparator: 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	Drug: Lenalidomide Other Names: CC-5013, Revlimid Drug: Rituximab Other Names: Rituxan

Arm

Intervention/Treatment

Experimental: 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

Drug: Lenalidomide

Other Names:

CC-5013, Revlimid

Drug: Rituximab

Other Names:

Rituxan

Active Comparator: 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

Drug: Lenalidomide

Other Names:

CC-5013, Revlimid

Drug: Rituximab

Other Names:

Rituxan

Outcome Measures

Primary Outcome Measures

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

Overall Survival [10 years]
Overall Survival is defined as the time between the first dose date of maintenance therapy and death from any cause
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)
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
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
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
Adverse Events [Up to 10 years]
Number of participants with adverse events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Local Institution - 055	Tucson	Arizona	United States	85710
2	Local Institution - 077	Little Rock	Arkansas	United States	72205
3	Local Institution - 079	Berkeley	California	United States	94704
4	John Muir Health	Concord	California	United States	94520
5	Sutter Hematology and Oncology	Sacramento	California	United States	95816
6	Local Institution - 032	San Diego	California	United States	92123
7	Local Institution - 130	Santa Barbara	California	United States	93105
8	Local Institution - 052	Boulder	Colorado	United States	80303
9	Local Institution - 106	Denver	Colorado	United States	80220
10	Colorado Cancer Research Program	Denver	Colorado	United States	80222
11	Local Institution - 062	Glenwood Springs	Colorado	United States	81601
12	Praxair Cancer Center Danbury	Danbury	Connecticut	United States	06810
13	Local Institution - 041	Norwalk	Connecticut	United States	06851
14	Hematology Oncology Associates, PC	Stamford	Connecticut	United States	06902
15	Local Institution - 149	Trumbull	Connecticut	United States	06611
16	Local Institution - 116	Waterbury	Connecticut	United States	067014
17	Cancer Specialists, LLC dba Cancer Specialists of North Florida	Fleming Island	Florida	United States	32003
18	Local Institution - 054	Ocala	Florida	United States	34474
19	Sacred Heart Medical Oncology Group	Pensacola	Florida	United States	32504
20	Local Institution - 011	Marietta	Georgia	United States	30060
21	Local Institution - 083	Newnan	Georgia	United States	30265
22	Local Institution - 108	Elk Grove Village	Illinois	United States	60007
23	United States Department of Veterans Affairs - VA Great Lakes Health Care System - Edward Hines Jr	Hines	Illinois	United States	60141
24	Local Institution - 159	Hinsdale	Illinois	United States	60521
25	Local Institution - 056	Niles	Illinois	United States	60714
26	Local Institution - 028	Park Ridge	Illinois	United States	60068
27	American Health Network of Indiana, LLC	New Albany	Indiana	United States	47150
28	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101-1733
29	Local Institution - 019	Fairway	Kansas	United States	66205
30	Local Institution - 350	Great Bend	Kansas	United States	67530
31	Local Institution - 138	Louisville	Kentucky	United States	40207
32	Maine General Medical Center	Waterville	Maine	United States	04901
33	Anne Arundel Medical Center	Annapolis	Maryland	United States	21401
34	Local Institution - 030	Baltimore	Maryland	United States	21204
35	Associates Of Oncology/Hematology, P.C.	Rockville	Maryland	United States	20850
36	Local Institution - 051	Ann Arbor	Michigan	United States	48106
37	Local Institution - 033	Lansing	Michigan	United States	48912
38	Local Institution - 164	Rochester	Minnesota	United States	55905
39	Local Institution - 050	Bolivar	Missouri	United States	65613
40	Local Institution - 103	Columbia	Missouri	United States	65212
41	Local Institution - 042	Saint Louis	Missouri	United States	63110
42	Mercy Medical Research Institute	Springfield	Missouri	United States	65804
43	Local Institution - 003	Lincoln	Nebraska	United States	68510
44	Local Institution - 098	Lebanon	New Hampshire	United States	03756
45	Summit Medical Group Overlook Oncology Center	Berkeley Heights	New Jersey	United States	07922
46	Veterans Affairs New Jersey Health Care System	East Orange	New Jersey	United States	07018
47	Local Institution - 080	Englewood	New Jersey	United States	07631
48	Regional Cancer Care Associates LLC	Mount Holly	New Jersey	United States	08060
49	Saint Peter'S University Hospital	New Brunswick	New Jersey	United States	08901
50	Brookdale University Hospital and Medical Center	Brooklyn	New York	United States	11212
51	C.R. Wood Cancer Center at Glens Falls Hospital	Glens Falls	New York	United States	12801
52	Broome Oncology, LLC	Johnson City	New York	United States	13790
53	Local Institution - 152	Lake Success	New York	United States	11042
54	Local Institution - 023	Kinston	North Carolina	United States	28501-1584
55	Local Institution - 039	Raleigh	North Carolina	United States	27607
56	Aultman Hospital	Canton	Ohio	United States	44710
57	Local Institution - 161	Cincinnati	Ohio	United States	45242
58	Local Institution - 047	Cleveland	Ohio	United States	44109
59	Local Institution - 045	Columbus	Ohio	United States	43219
60	Toledo Clinic Cancer Center	Toledo	Ohio	United States	43623
61	Local Institution - 037	Oklahoma City	Oklahoma	United States	73104
62	Local Institution - 059	Eugene	Oregon	United States	97401
63	Hematology Oncology Associates, P.C.	Medford	Oregon	United States	97504
64	Local Institution - 073	Greenville	South Carolina	United States	29615
65	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
66	Local Institution - 153	Sioux Falls	South Dakota	United States	57105
67	Baptist Cancer Center	Memphis	Tennessee	United States	38104
68	Local Institution - 076	Memphis	Tennessee	United States	38104
69	Texas Oncology, P.A.- Amarillo	Amarillo	Texas	United States	79106
70	Arlington Cancer Center	Arlington	Texas	United States	76012
71	Texas Oncology-Arlington South	Arlington	Texas	United States	76014
72	Local Institution - 105	Dallas	Texas	United States	75230
73	Local Institution - 026	Houston	Texas	United States	77030
74	Local Institution - 067	Houston	Texas	United States	77030
75	Local Institution - 008	Houston	Texas	United States	77090
76	Texas Health Physicians Group	Plano	Texas	United States	75093
77	Local Institution - 071	Round Rock	Texas	United States	78681
78	Local Institution - 070	San Antonio	Texas	United States	78217
79	Local Institution - 058	San Antonio	Texas	United States	78240
80	Local Institution - 111	Temple	Texas	United States	66205
81	Tyler Hematology and Oncology	Tyler	Texas	United States	75701
82	Local Institution - 163	Tyler	Texas	United States	75702
83	Texas Oncology, P.A. - Deke Slayton Cancer Center	Webster	Texas	United States	77598-4420
84	Local Institution - 090	Salt Lake City	Utah	United States	84106
85	Rutland Regional Medical Center	Rutland	Vermont	United States	05701
86	Local Institution - 053	Christiansburg	Virginia	United States	24073
87	Fort Belvoir Community Hospital	Fort Belvoir	Virginia	United States	22060
88	Local Institution - 081	Norfolk	Virginia	United States	23502
89	PeaceHealth St. Joseph Medical Center	Bellingham	Washington	United States	98225
90	Local Institution - 049	Gig Harbor	Washington	United States	98332
91	Local Institution - 119	Olympia	Washington	United States	98502
92	Local Institution - 104	Vancouver	Washington	United States	98684
93	Local Institution - 099	Walla Walla	Washington	United States	99362
94	Local Institution - 006	Wenatchee	Washington	United States	98801
95	Local Institution - 038	Morgantown	West Virginia	United States	26506
96	Aurora Health Care Aurora Research	Milwaukee	Wisconsin	United States	53233
97	Local Institution - 301	Mukwonago	Wisconsin	United States	53145
98	Local Institution - 300	Oconomowoc	Wisconsin	United States	53066
99	Local Institution - 101	Waukesha	Wisconsin	United States	53188-5099
100	Local Institution - 208	Berlin		Germany	10707
101	Local Institution - 202	Bremen		Germany	28177
102	Local Institution - 205	Frankfurt		Germany	60389
103	Local Institution - 211	Frechen		Germany	50226
104	Local Institution - 200	Gießen		Germany	35392
105	Local Institution - 203	Hannover		Germany	30171
106	Local Institution - 206	Kassel		Germany	34119
107	Local Institution - 213	Köln		Germany	50677
108	Local Institution - 210	Marburg		Germany	35037
109	Local Institution - 204	Munchen		Germany	81241
110	Local Institution - 215	Mönchengladbach		Germany	41063
111	Local Institution - 212	Münster		Germany	48149
112	Local Institution - 201	Potsdam		Germany	14467
113	Local Institution - 207	Ravensberg		Germany	88212
114	Local Institution - 209	Würzburg		Germany	97080
115	Local Institution - 029	San Juan		Puerto Rico	00919-1227