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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 August 2014 by Celgene Corporation
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01996865
First received: November 22, 2013
Last updated: August 22, 2014
Last verified: August 2014
  Purpose

This Phase 3B multicenter, randomized (stratified by histology, lines of anti-lymphoma therapy and age), open label study will enroll subjects with relapsed/refractory follicular lymphoma (FL), marginal zone lymphoma (MZL) or mantle cell lymphoma (MZL). All subjects will receive 12 Cycles of lenalidomide plus rituximab induction therapy. The study is designed to compare the efficacy and safety of two maintenance regimens following induction therapy. Subjects will be randomized at study start to lenalidomide plus rituximab combination therapy (for 18 Cycles) followed by lenalidomide single-agent maintenance (to progression; Arm A, experimental) versus rituximab single-agent maintenance (for 18 Cycles; Arm B, control). The study is divided into a Screening Period, a Treatment Period (induction and maintenance), and a Follow up Period. Approximately 500 subjects are planned to be randomized.


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 Maintenance 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: October 2022
Estimated Primary Completion Date: January 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:

Follicular lymphoma (FL), marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL) are cancers of the B lymphocyte, a type of white blood cell. Lenalidomide is an immunomodulatory drug (a drug that affects the immune system) which alters the body's immune system and it may also interfere with the development of tiny blood vessels involved in tumor growth. Therefore, lenalidomide may reduce or prevent the growth of cancer cells. Lenalidomide has also been shown to restore the immune cells' ability to attack and kill tumor cells, an ability that may be inhibited by FL and other lymphomas. The combination of rituximab and lenalidomide may eliminate the cancer while restoring the immune system's ability to attack tumor cells.

Subjects must have an investigator assessed diagnosis of relapsed/refractory Grade 1, 2, or 3a follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL), Stage I to IV, have been previously treated for their lymphoma with at least one prior line of systemic chemotherapy, immunotherapy, or chemoimmunotherapy; have at least one measurable nodal or extranodal lesion by computed axial tomography (CT) or magnetic resonance imaging (MRI) scan, and have adequate bone marrow function, liver function, and renal function.

Subjects with either follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL) will be randomized to Arm A will receive lenalidomide plus rituximab for up to 30 Cycles (12 induction Cycles then 18 maintenance Cycles) followed by lenalidomide single-agent maintenance (to disease progression [PD]).

Subjects with either follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL) will be randomized to Arm B will receive lenalidomide plus rituximab for 12 Cycles (induction) followed by rituximab single-agent for 18 Cycles (maintenance). Cycle length in both arms is 28-days.

Efficacy determination for the primary endpoint will be based upon progression free survival (PFS).

  Eligibility

Ages Eligible for Study:   18 Years and older
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: Mary Bartlett, Sr Study Manager 913-271-6400 MBartlett@celgene.com
Contact: Jorge Mouro, Associate Dir, Lymphoma/CLL 908-673-2252 jmouro@celgene.com

  Show 37 Study Locations
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Kenneth Foon, VP, Med Affairs Celgene Corporation
  More Information

No publications provided

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: August 22, 2014
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
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Lenalidomide
Rituximab
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents
Antirheumatic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Leprostatic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014