Rituximab Plus Lenalidomide for Patients With Relapsed / Refractory Indolent Non-Hodgkin's Lymphoma (Follicular Lymphoma and Marginal Zone Lymphoma)
Condition: Lymphoma, Non-Hodgkin
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Intervention: Rituximab; Lenalidomide; Placebo
Intervention description: Rituximab 375mg/m^2 IV every week in Cycle 1 (Days 1, 8, 15 and 22) on Day 1 of every 28 day cycle from Cycles 2 to 5; Lenalidomide 20mg by mouth (PO) daily on Days 1 to 21 every 28 days up to 12 cycles; Placebo (identical matched capsule) PO daily on Days 1 to 21 every 28 days
Intervention MeSH terms: Rituximab; Lenalidomide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 358.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non-Hodgkins Follicular lymphoma, Non-Hodgkins Marginal zone lymphoma, treatment for follicular lymphoma, treatment for Marginal zone lymphoma

Summary:

      This double-blind randomized, parallel group study will evaluate the efficacy and safety of
      lenalidomide (Revlimid, CC-5013) in combination with rituximab (MabThera/Rituxan) in patients
      with relapsed or refractory follicular lymphoma or marginal zone lymphoma. Patients will be
      randomized to receive either lenalidomide or placebo for twelve 28-day cycles in combination
      with rituximab. Anticipated time on study treatment is 1 year.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥18 years at the time of signing the informed consent document.

          -  Understand and voluntarily sign an informed consent document prior to any study
             related assessments/procedures are conducted.

          -  Histologically confirmed marginal zone lymphoma or follicular lymphoma (grade 1, 2 or
             3a; CD20+ by flow cytometry or histochemistry).

          -  Previously treated with at least one prior systemic chemotherapy, immunotherapy or
             chemoimmunotherapy and have received at least 2 previous doses of rituximab.

          -  Documented relapsed, refractory or progressive disease after treatment with systemic
             therapy and must not be rituximab-refractory.

          -  Investigator considers rituximab monotherapy appropriate.

          -  Bi-dimensionally measurable disease on cross sectional imaging by X-ray computed
             tomography (CT) or magnetic resonance imaging (MRI).

          -  Need of treatment for relapsed, progressed or refractory disease as assessed by the
             investigator.

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

          -  Adequate bone marrow function.

          -  Willingness to follow study visit schedule, pregnancy precautions and other protocol
             requirements.

        Exclusion Criteria:

          -  Histology other than follicular or marginal zone lymphoma or clinical evidence of
             transformation or Grade 3b follicular lymphoma.

          -  Subjects taking corticosteroids during the last week prior to study treatment, unless
             administered at a dose equivalent to < 20 mg/day prednisone or prednisolone.

          -  Systemic anti-lymphoma therapy within 28 days or use of antibody agents within 8 weeks
             use of radioimmunotherapy within 6 months.

          -  Known seropositive for or active viral infection with hepatitis B virus (HBV) or/and
             human immunodeficiency virus (HIV).

          -  Known hepatitis C virus (HCV) positive with chronic HCV or active viral infection with
             HCV hepatitis requiring anti-viral medication (at time of randomization).

          -  Life expectancy < 6 months.

          -  Known sensitivity or allergy to murine products.

          -  Prior history of malignancies, other than follicular or marginal zone lymphoma, unless
             the subject has been free of the disease for ≥ 5 years.

          -  Prior use of lenalidomide.

          -  Known allergy to thalidomide.

          -  Neuropathy > Grade 1.

          -  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.

          -  Uncontrolled intercurrent illness.

          -  Any significant medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the subject from signing the informed consent document.

          -  Pregnant or lactating females.

          -  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.