Lenalidomide and Rituximab in Subjects With Previously Untreated Indolent Non-Hodgkin's Lymphoma

Phase II Study of Lenalidomide and Rituximab in Subjects With Previously Untreated Indolent Non Hodgkin's Lymphoma

Lenalidomide has been shown to have single agent activity in indolent Non-Hodgkin's Lymphoma. It is approved for the treatment of multiple myeloma and myelodysplastic syndrome.

Rituximab is effective as a single agent and in combination with chemotherapy for indolent Non-Hodgkin's Lymphoma.

The purpose of this study is to see how well giving lenalidomide together with rituximab works in treating patients with previously untreated indolent Non Hodgkin's Lymphoma.

Lenalidomide will taken at 20 mg daily, days 1-21 of a 28 day cycle, to be continued until the disease progresses, unacceptable side effects or after twelve cycles if the patient is responding well.

Rituximab 375 mg/m2/wk x 4 weeks will begin on Day 15 of cycle 1. After 4 cycles of therapy, if patients respond well to treatment, patients will receive a second course of Rituximab.

Blood samples will be collected to assess how the immune system is functioning.

Inclusion Criteria:

1. All patients must be informed of the investigative nature of the clinical trial and given written informed consent in accordance with institutional and federal guidelines.

2. Age greater than or equal to 18 years at the time of signing the informed consent form.

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

4. Previously untreated, histologically confirmed indolent lymphoma including follicle cell lymphoma, WHO classification, grade I or II, and marginal zone lymphoma. Bone marrow biopsies as the sole means of diagnosis are not acceptable, but they may be submitted in conjunction with nodal biopsies. Fine needle aspirates are not acceptable.

5. At least one measurable lesion according to the International Working Group Response criteria for lymphomas. There must be measurable lymphadenopathy to follow with serial exam and/or imaging.

6. Submission of original biopsy for review by local staff hematopathologist.

7. ECOG performance status of 0 -2 at study entry.

8. No major organ dysfunction with laboratory test results within these ranges:

   • Absolute neutrophil count greater than or equal to 1000 /uL
   • Platelet count greater than or equal to 75 x 109/L
   • Total bilirubin less than or equal to 2.0 mg/dL.
   • HIV negative
   • Subjects must have calculated creatinine clearance ≥ 30ml/min by Cockcroft-Gault formula. See section below, "Dosing Regimen", regarding lenalidomide dose adjustment for calculated creatinine clearance ≥ 30ml/min and < 60ml/min.

9. Life expectancy of greater than 3 months.

10. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting lenalidomide and 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. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.

11. Disease free of prior malignancies for greater than or equal to 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast

12. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation. (patients who are intolerant to aspirin may use low molecular weight heparin).

13. Must be able to swallow lenalidomide capsules.

Exclusion Criteria:

1. Any prior treatment for Non-Hodgkin's Lymphoma.
2. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
3. Pregnant or breast-feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
4. 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.
5. Use of any other experimental drug or therapy within 28 days of baseline.
6. Known hypersensitivity to thalidomide or rituximab.
7. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
8. Any prior use of lenalidomide.
9. Concurrent use of other anti-cancer agents or treatments.
10. Known positive for HIV
11. Known active hepatitis, type A, B or C.
12. Evidence for CNS metastatic disease
13. Subjects with ≥ Grade 2 neuropathy