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.
Active, not recruiting
Phase 3
| Drug | Synonyms | Arms |
|---|---|---|
| Lenalidomide | CC-5013, Revlimid | Arm A: Lenalidomide + rituximab followed by lenalidomide |
| Rituximab | Rituxan | Arm A: Lenalidomide + rituximab followed by lenalidomide |
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.
| Name | Type | Description | Interventions |
|---|---|---|---|
| Arm A: Lenalidomide + rituximab followed by lenalidomide | Experimental | 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 a 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 | Active Comparator | 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 |
|
Inclusion Criteria:
-- Age ≥18 years
- Histologically confirmed Follicular Lymphoma (Grade 1, 2 or 3a), 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 8 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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Progression free survival (PFS) for Follicular lymphoma (FL), marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL) |
| Time Frame: | Up to 8 years |
| Safety Issue: | |
| Description: | Progression free survival is defined as the time from randomization into the study to the first observation of documented disease progression or death due to any cause |
| Measure: | Adverse Events |
| Time Frame: | Up to 8 years |
| Safety Issue: | |
| Description: | Number of participants with adverse events |
| Measure: | Complete response rate |
| Time Frame: | 8 years |
| Safety Issue: | |
| Description: | 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) |
| Measure: | Overall response rate |
| Time Frame: | 8 years |
| Safety Issue: | |
| Description: | 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). |
| Measure: | Duration of response |
| Time Frame: | 8 years |
| Safety Issue: | |
| Description: | Duration of response is defined as the time from the initial response (at least partial remission) to documented disease progression |
| Measure: | Duration of complete response |
| Time Frame: | 8 years |
| Safety Issue: | |
| Description: | Duration of complete response is defined as the time from the first evidence of CR/CRu to documented disease progression |
| Measure: | Time to the next anti-lymphoma treatment |
| Time Frame: | 8 years |
| Safety Issue: | |
| Description: | Duration of response is defined as time from initial response of at least a PR to documented progression/relapse |
| Measure: | Time to treatment failure |
| Time Frame: | 8 years |
| Safety Issue: | |
| Description: | Time to treatment failure is defined as the time from the date of randomization to discontinuation of treatment for any reason, including disease progression, treatment toxicity or death |
| Measure: | Time to histological transformation |
| Time Frame: | 8 years |
| Safety Issue: | |
| Description: | Time to histological transformation is defined as the time from the date of randomization to time to histological transformation as measured based on documentation of histological transformation |
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Celgene |
August 5, 2021
