Rituximab Plus Lenalidomide for Patients With Relapsed / Refractory Indolent Non-Hodgkin's Lymphoma (Follicular Lymphoma and Marginal Zone Lymphoma) (AUGMENT)

Celgene

Status and phase: Completed; Phase 3

Conditions: Lymphoma, Non-Hodgkin

Treatments: Drug: Rituximab; Drug: Lenalidomide; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01938001

CC-5013-NHL-007

Details and patient eligibility

About

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.

Full description

Indolent lymphoma is a slow growing but incurable lymphoma which includes follicular lymphoma and marginal zone lymphoma. Follicular lymphoma and marginal zone lymphoma 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 follicular lymphoma and other lymphomas. The combination of rituximab and lenalidomide may eliminate the cancer while restoring the immune system's ability to attack tumor cells.

Enrollment: 358 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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358 participants in 2 patient groups

Rituximab and Lenalidomide

Experimental group

Description:

Participants received rituximab 375 mg/m\^2 intravenously (IV) every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from Cycles 2 to 5 plus lenalidomide 20 mg by mouth (PO) once daily on Days 1 to 21 every 28 days, up to 12 cycles (21-day treatment and 7-day rest period); if creatinine clearance (CrCl) was ≥ 30 mL/min but \< 60 mL/min, participants received lenalidomide 10 mg capsules on days 1 to 21 every 28 days.

Treatment:

Drug: Rituximab

Drug: Lenalidomide

Rituximab and Placebo

Active Comparator group

Description:

Participants received riituximab 375 mg/m\^2 IV every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from cycle 2 to 5 plus placebo (identically matched capsule) once daily on Days 1 to 21 of every 28-day cycle up, to 12 cycles.

Treatment:

Drug: Rituximab

Drug: Placebo