Lenalidomide Plus Rituxan for Untreated Mantle Cell Lymphoma

Phase II Study of Lenalidomide Plus Rituximab in Patients With Previously Untreated Mantle Cell Lymphoma

This is a phase II, multicenter study to determine the efficacy and safety of first-line lenalidomide plus rituximab therapy in patients with mantle cell lymphoma who have received no prior systemic therapy.

Induction Phase (week 1 - 48):

• Lenalidomide will be given at 20 mg/day for days 1-21 of a 28-day cycle for 12 cycles. If no excess toxicity is observed the dose will be increased to 25 mg/day.
• Rituximab will be administered at 375 mg/m2 per dose for a total of 9 doses. The first 4 doses will be administered weekly starting on day 1 of lenalidomide (e.g. days 1, 8, 15 and 22). Subsequent rituximab doses will be administered for one dose each at weeks 12, 20, 28, 36 and 44.

Maintenance Phase (week 49 - progression of disease):

• Lenalidomide will be given at 15 mg/day for days 1-21 of a 28-day cycle.
• Rituximab at 375 mg/m2 per dose will be administered for one dose every 8 weeks, starting at week 52.

Response Assessment

• Year 1-2: Conventional restaging CT scan (or MRI) with IV contrast every 3 months from cycle 1 day 1 of the study.
• Year 3 onwards: Conventional restaging CT scan (or MRI) with IV contrast every 6 months until progression.

Inclusion Criteria:

• Understand and voluntarily sign an informed consent form.

• Age > = 18 years at the time of signing the informed consent form.

• Able to adhere to the study visit schedule and other protocol requirements.

• Histologically confirmed diagnosis of mantle cell Non-Hodgkin's Lymphoma with cyclin D1 overexpression by immunohistochemistry, and a characteristic immunophenotypic profile with CD5(+), CD23(-), CD20(+), and CD10(-). In tumor tissues with negative cyclin D1, evidence of cyclin D2 or D3 overexpression by immunohistochemistry will be acceptable.

• No prior systemic therapy for lymphoma including chemotherapy or immunotherapy. Patients may have received involved-field radiation therapy which has been discontinued at least 4 weeks prior to treatment in this study.

• Patient has measurable disease as defined by a tumor mass > 1.5 cm in one dimension.

• Low and intermediate-risk disease as defined by MIPI score.

• Subject who the investigator considers that chemotherapy is not indicated.

• ECOG performance status of < = 2 at study entry.

• Laboratory test results within these ranges:

  • Absolute neutrophil count > = 1000 /mm³
  • Platelet count > = 75,000 /mm³
  • Calculated creatinine clearance ≥ 30 ml/min by Cockcroft-Gault formula • Total bilirubin < = 2 x ULN
  • AST (SGOT) and ALT (SGPT) < = 3 x ULN.

• Disease free of prior malignancies for > = 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, carcinoma "in situ" of the cervix or breast, or localized prostate cancer.

• All subjects must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.

• Subjects of reproductive potential agree to use birth control throughout their participation in this study, and for three months following study termination.

• Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days). FCBP must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. See Appendix: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.

• Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).

• Asymptomatic carriers of hepatitis B virus can be considered for study if they agree to and comply with close monitoring and suppressive therapy with lamivudine during treatment and for additional six months after coming off study.

Exclusion Criteria:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Pregnant or breast feeding females.
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Use of any other experimental drug or therapy within 28 days of baseline.
• Patient on corticosteroids within two weeks prior to study entry, except for prednisone < = 10 mg/day or equivalent for purposes other than treating MCL.
• Known hypersensitivity to thalidomide.
• Any prior use of lenalidomide.
• Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.
• Known central nervous system (CNS) involvement by lymphoma.
• Patient at high risk for deep vein thrombosis not willing to take DVT prophylaxis.
• Patient has had major surgery within the last 3 weeks