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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2016 by Celgene Corporation
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01996865
First received: November 22, 2013
Last updated: May 18, 2016
Last verified: May 2016
  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.

Condition Intervention Phase
Lymphoma, Non-Hodgkin
Drug: Lenalidomide
Drug: Rituximab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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 in Subjects With Relapsed/Refractory Follicular, Marginal Zone, or Mantle Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Progression free survival (PFS) for Follicular lymphoma (FL), marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL) [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]
    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:
  • Adverse Events [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]
    Number of participants with adverse events

  • Complete response rate [ Time Frame: 8 years ] [ Designated as safety issue: No ]
    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)

  • Overall response rate [ Time Frame: 8 years ] [ Designated as safety issue: No ]
    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).

  • Duration of response [ Time Frame: 8 years ] [ Designated as safety issue: No ]
    Duration of response is defined as the time from the initial response (at least partial remission) to documented disease progression

  • Duration of complete response [ Time Frame: 8 years ] [ Designated as safety issue: No ]
    Duration of complete response is defined as the time from the first evidence of CR/CRu to documented disease progression

  • Time to the next anti-lymphoma treatment [ Time Frame: 8 years ] [ Designated as safety issue: No ]
    Duration of response is defined as time from initial response of at least a PR to documented progression/relapse

  • Time to treatment failure [ Time Frame: 8 years ] [ Designated as safety issue: No ]
    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

  • Time to histological transformation [ Time Frame: 8 years ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 500
Study Start Date: April 2014
Estimated Study Completion Date: March 2023
Estimated Primary Completion Date: February 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 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
Drug: Lenalidomide
Other Name: CC-5013, Revlimid
Drug: Rituximab
Other Name: 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 Name: CC-5013, Revlimid
Drug: Rituximab
Other Name: Rituxan

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01996865

Contacts
Contact: Dipa Kumar, Sr Study Manager 908-897-6510 dkumar@celgene.com
Contact: Mary Llorente, Assoc Dir, USMA Lymphoma/CLL mllorente@celgene.com

  Show 84 Study Locations
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Kenneth Foon, VP, Med Affairs Celgene
  More Information

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01996865     History of Changes
Other Study ID Numbers: CC-5013-NHL-008 
Study First Received: November 22, 2013
Last Updated: May 18, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Celgene Corporation:
Lymphoma, Mantle cell Lymphoma, Follicular Lymphoma, Marginal zone Lymphoma, Lenalidomide treatment, rituximab treatment, Non Hodgkins Lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lenalidomide
Rituximab
Thalidomide
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 24, 2016