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

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ClinicalTrials.gov Identifier: NCT01996865

Recruitment Status : Recruiting

First Posted : November 27, 2013

Last Update Posted : March 15, 2019

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Sponsor:

Information provided by (Responsible Party):

Celgene

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.

Condition or disease	Intervention/treatment	Phase
Lymphoma, Non-Hodgkin	Drug: Lenalidomide Drug: Rituximab	Phase 3

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	500 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (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
Actual Study Start Date :	April 2, 2014
Estimated Primary Completion Date :	April 8, 2023
Estimated Study Completion Date :	July 8, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Drug Information available for: Rituximab Lenalidomide

Genetic and Rare Diseases Information Center resources: Lymphosarcoma Follicular Lymphoma Marginal Zone Lymphoma Mantle Cell Lymphoma

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
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

Arm

Intervention/treatment

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

Outcome Measures

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 ]
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 ]
Number of participants with adverse events
Complete response rate [ Time Frame: 8 years ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01996865

Contacts

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Contact: Caroline Labe, Clinical Trial Manager	617-710-7065	clabe@celgene.com
Contact: Mary Llorente, Assoc Dir, USMA Lymphoma/CLL		mllorente@celgene.com

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Sponsors and Collaborators

Celgene

Investigators

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Study Director:	Kenneth Foon, VP, Med Affairs	Celgene

More Information

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Responsible Party:	Celgene
ClinicalTrials.gov Identifier:	NCT01996865 History of Changes
Other Study ID Numbers:	CC-5013-NHL-008
First Posted:	November 27, 2013 Key Record Dates
Last Update Posted:	March 15, 2019
Last Verified:	March 2019

Keywords provided by Celgene:


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

Additional relevant MeSH terms:

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Lymphoma Lymphoma, Mantle-Cell Lymphoma, Non-Hodgkin Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Rituximab	Lenalidomide Antineoplastic Agents, Immunological Antineoplastic Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Growth Inhibitors

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