Clinical Trials /

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

NCT01996865

Description:

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.

Related Conditions:
  • Follicular Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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 in Subjects With Relapsed/Refractory Follicular, Marginal Zone, or Mantle Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: CC-5013-NHL-008
  • NCT ID: NCT01996865

Conditions

  • Lymphoma, Non-Hodgkin

Interventions

DrugSynonymsArms
LenalidomideCC-5013, RevlimidArm A: Lenalidomide + rituximab followed by lenalidomide
RituximabRituxanArm A: Lenalidomide + rituximab followed by lenalidomide

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A: Lenalidomide + rituximab followed by lenalidomideExperimentalInduction 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
  • Lenalidomide
  • Rituximab
Arm B: Lenalidomide + rituximab followed by rituximabActive ComparatorInduction 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
  • Lenalidomide
  • Rituximab

Eligibility Criteria

        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

Primary Outcome Measures

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

Secondary Outcome Measures

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

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Celgene

Trial Keywords

  • Lymphoma, Mantle cell Lymphoma, Follicular Lymphoma, Marginal zone Lymphoma, Lenalidomide treatment, rituximab treatment, Non Hodgkins Lymphoma

Last Updated

August 20, 2019