NCT01996865 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2025-07-10

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

Progression Free Survival (PFS)

→

outcome · POSTED

Overall Survival (OS)

→

outcome · POSTED

Improvement of Response (IOR)

→

outcome · POSTED

Overall Response Rate (ORR)

→

outcome · POSTED

Complete Response Rate (CRR)

→

outcome · POSTED

Duration of Response (DOR)

→

outcome · POSTED

Time to Next Anti-lymphoma Treatment

→

outcome · POSTED

Time to Histological Transformation

→

outcome · POSTED

Duration of Complete Response (DOCR)

→

outcome · POSTED

Participants Experiencing Treatment Emergent Adverse Events (TEAEs)

→

outcome · POSTED

Participants Experiencing Adverse Events Related to Vital Signs

→

outcome · POSTED

Participants With Grade 3 or Grade 4 Hematology Parameters

→

outcome · POSTED

Participants With Grade 3 or Grade 4 Serum Chemistry Parameters

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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
intervention Names
Drug: Lenalidomide
Drug: Rituximab
label
Arm A: Lenalidomide + rituximab followed by lenalidomide
type
EXPERIMENTAL
description
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
intervention Names
Drug: Lenalidomide
Drug: Rituximab
label
Arm B: Lenalidomide + rituximab followed by rituximab
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Arm A: Lenalidomide + rituximab followed by lenalidomide
Arm B: Lenalidomide + rituximab followed by rituximab
name
Lenalidomide
other Names
CC-5013, Revlimid
type
DRUG
arm Group Labels
Arm A: Lenalidomide + rituximab followed by lenalidomide
Arm B: Lenalidomide + rituximab followed by rituximab
name
Rituximab
other Names
Rituxan
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 503
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Progression free survival (PFS) is defined as the time from the date of first dose of maintenance therapy to the date of the first objective documentation of tumor progression or death due to any cause. Analysis was based on Kaplan Meier estimates. The PFS events were determined using a modification of the IWG 1999 criteria.
measure
Progression Free Survival (PFS)
time Frame
From the first dose date of maintenance therapy to objective disease progression or death from any cause, whichever occurs first (up to approximately 432 weeks)

secondary Outcomes

description
Overall Survival (OS) is defined as the time between the first dose date of maintenance therapy and death from any cause. Participants who complete the study and are still alive at the time of the clinical data cutoff date will be censored at the last visit date or the last contact date, whichever is later. Participants who were lost to follow-up prior to the clinical data cut-off date will also be censored at the time of the last contact. Analysis was based on Kaplan Meier estimates and Hazard Ratio (HR).
measure
Overall Survival (OS)
time Frame
From the first dose date of maintenance therapy to death from any cause (up to approximately 480 weeks)
description
Improvement of Response (IOR) is the percentage of participants with improved tumor response during the maintenance phase (converted from partial response at end of induction to complete response or complete response unconfirmed as best response) and participants who converted from stable disease at the end of induction period to partial response or better as best response during maintenance phase.
measure
Improvement of Response (IOR)
time Frame
From the first dose date of maintenance therapy to death from any cause (up to approximately 432 weeks)
description
The overall response rate (ORR) is defined as the percentage of participants with a best response of at least partial response (including complete response, complete response unconfirmed and partial response) after the first dose date of maintenance therapy and prior to any treatment change.
measure
Overall Response Rate (ORR)
time Frame
From the first dose date of maintenance therapy up to CR, CRu, PR, or treatment change (up to approximately 432 weeks)
description
Best Complete Response Rate (CRR), defined as the proportion of participants with a best response of at least CRu (including CR and CRu) after the first dose date of maintenance therapy and prior to any treatment change.
measure
Complete Response Rate (CRR)
time Frame
From the first dose date of maintenance therapy up to CR or CRu (up to approximately 432 weeks)
description
DOR is from initial response (at least CRu) after the first dose date of maintenance therapy and prior to treatment change to documented disease progression or death. Participants who have not progressed or died at the time of the clinical data cutoff date will be censored at the last assessment showing no progression. Participants who change treatment without evidence of disease progression will be censored at the last assessment showing no progression prior to treatment change. Analysis was based on Kaplan Meier estimates.
measure
Duration of Response (DOR)
time Frame
From the initial response (at least PR) after the first dose date of maintenance therapy and prior to treatment change to documented disease progression or death, whichever occurs first (up to approximately 432 weeks)
description
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. Participants without new treatment therapy will be censored at the last visit. Analysis was based on Kaplan Meier estimates.
measure
Time to Next Anti-lymphoma Treatment
time Frame
From the first dose date of maintenance therapy to the time of first documented administration of new anti-lymphoma therapy (up to approximately 300 weeks)
description
Time to histological transformation is defined as from the first dose date of maintenance therapy to the time of histological transformation as measured based on documentation of histological transformation (as assessed by the investigator). Analysis was based on Kaplan Meier estimates. In case of clinical suspicion of transformation, including rapid disease progression, unexpected changes in "B" symptoms or rapidly increasing LDH, a biopsy should be performed. In this clinical trial, histological transformation will be considered disease progression. This endpoint will not be calculated for participants randomized with transformed Follicular Lymphoma (tFL).
measure
Time to Histological Transformation
time Frame
From the first dose date of maintenance therapy to the time of histological transformation (up to approximately 432 weeks)
description
Duration of complete response (DOCR) is calculated as the time from the initial response (CR or CRu) after the first dose date of maintenance therapy and prior to treatment change to documented disease progression or death. Analysis was based on Kaplan Meier estimates. Participants who have not progressed or died at the time of the clinical data cutoff date will be censored at the last assessment showing no progression. Participants who change treatment without evidence of disease progression will be censored at the last assessment showing no progression prior to treatment change.
measure
Duration of Complete Response (DOCR)
time Frame
From the initial CR/CRu after the first dose date of maintenance therapy and prior to treatment change to documented disease progression or death, whichever occurs first (up to approximately 432 weeks)
description
Number of participants experiencing AEs, SAEs, AEs leading to study discontinuation, and AEs of interest (AEIs). An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. SAEs is any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization; results significant disability; or is a congenital anomaly/birth defect. TEAEs are defined as AEs with an onset date on or after the first dose of study treatment up to 30 days after the last dose of study treatment in the study, or if a pre-existing condition worsens in severity or becomes serious after receiving the first dose of study treatment.
measure
Participants Experiencing Treatment Emergent Adverse Events (TEAEs)
time Frame
From first dose up to 30 days after last dose (up to approximately 64 weeks for induction period and 427 weeks for maintenance period)
description
The number of participants who experienced adverse events related to vital sign measurements
measure
Participants Experiencing Adverse Events Related to Vital Signs
time Frame
From first dose up to 30 days after last dose (up to approximately 64 weeks for induction period and 427 weeks for maintenance period)
description
Clinical laboratory values in induction period include any laboratory values that are taken after the first dose date of induction therapy through 28 days after the last dose date of induction therapy or before the first dose date of maintenance therapy, whichever is earlier. Graded according to the NCI CTCAE version 4.03, except for tumor flare reaction, which is accessed using NCI CTCAE version 3.0. Participants with zero maximum grade are excluded.
measure
Participants With Grade 3 or Grade 4 Hematology Parameters
time Frame
From first dose up to 30 days after last dose (up to approximately 64 weeks for induction period and 427 weeks for maintenance period)
description
Clinical laboratory values in induction period include any laboratory values that are taken after the first dose date of induction therapy through 28 days after the last dose date of therapy. Graded according to the NCI CTCAE version 4.03, except for tumor flare reaction, which is accessed using NCI CTCAE version 3.0. Participants with zero maximum grade are excluded.
measure
Participants With Grade 3 or Grade 4 Serum Chemistry Parameters
time Frame
From first dose up to 30 days after last dose (up to approximately 64 weeks for induction period and 427 weeks for maintenance period)

Full 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.
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.

Source references

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.
pmid
30897038
type
BACKGROUND
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.
pmid
30919940
type
BACKGROUND