Phase II Trial of Revlimid® and Rituximab for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
Condition: Chronic Lymphocytic Leukemia; CLL
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Revlimid; Rituximab
Intervention MeSH terms: Rituximab; Lenalidomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Chronic Lymphocytic Leukemia; CLL; Relapsed or Refractory; previously treated

Summary:

      The Chronic Lymphocytic Leukemia (CLL) Research Consortium (CRC) is conducting a two-arm,
      multi-center phase II trial of Revlimid® and rituximab for Relapsed or Refractory CLL for
      patients under the age of 65 and patients 65 years and older.

      Lenalidomide (Revlimid) is an immunomodulatory agent with promising clinical activity in CLL
      and is FDA approved for treatment of relapsed multiple myeloma and 5q-myelodysplastic
      syndrome. Rituximab (Rituxan) is a monoclonal antibody to CD20 that is approved for the
      treatment of CLL.

      The primary objective of this study is to determine the overall response rate of the
      combination of Revlimid® and rituximab in previously treated CLL patients. All patients will
      receive treatment with Revlimid® starting at a low dose that will be dose escalated based on
      individual patient tolerability. The combination of Revlimid and Rituximab will be
      administered for a maximum of 7 cycles. Patients with residual leukemia following seven
      cycles of treatment with the combination may elect to continue on protocol for an additional
      6 cycles of single agent Revlimid® consolidation.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosis of chronic lymphocytic leukemia (CLL).

          2. Subjects must have active disease appropriate for therapy.

          3. Previous treatment for CLL

          4. Understand and voluntarily sign an informed consent form.

          5. Age ≥18 years at the time of signing the informed consent form.

          6. Able to adhere to the study visit schedule and other protocol requirements.

          7. ECOG performance status of ≤ 2 at study entry (see Appendix B).

          8. Laboratory test results within these ranges: Absolute neutrophil count ≥ 1.0 x
             109/L,Platelet count ≥ 50 x 109/L, Total bilirubin ≤ 1.5 mg/dL, AST (SGOT) and ALT
             (SGPT) ≤ 2 x ULN, Creatinine clearance estimated to be ≥ 30 ml/min

          9. Disease free of prior malignancies for ≥ 2 years with exception of currently treated
             basal cell, squamous cell carcinoma of the skin, or carcinoma in situ" of the cervix
             or breast.

         10. 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 prior to
             and again within 24 hours of starting Revlimid® 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 Revlimid®. 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. See Appendix: Risks of Fetal Exposure, Pregnancy Testing Guidelines and
             Acceptable Birth Control Methods, AND also Appendix: Education and Counseling Guidance
             Document.

        Exclusion Criteria:

          1. Known Hepatitis B Ag positive, Hepatitis C positive patients.

          2. Known HIV positive patients.

          3. Patients with uncontrolled Autoimmune Hemolytic Anemia (AIHA) or autoimmune
             thrombocytopenia (ITP).

          4. Inability to provide informed consent.

          5. Concurrent malignancy (excluding basal and squamous cell skin cancers).

          6. Active fungal, bacterial, and/or viral infection.

          7. Any serious medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the subject from signing the informed consent form.

          8. Pregnant or breast-feeding females. (Lactating females must agree not to breast feed
             while taking Revlimid®).

          9. 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.

         10. Use of any other experimental drug or therapy within 28 days of baseline.

         11. Known hypersensitivity to thalidomide.

         12. The development of erythema nodosum if characterized by a desquamating rash while
             taking thalidomide or similar drugs.

         13. Concurrent use of other anti-cancer agents or treatments.

         14. Patients with history of deep venous thrombus or pulmonary embolism. Patients who are
             at increased risk of thrombosis during treatment with Revlimid® including those taking
             concurrent erythropoietin, darbepoetin or high-dose corticosteroids are also excluded.

         15. Patients with a history of embolic events (e.g. TIA) from arrhythmia or peripheral
             arterial disease or of recent mycocardial infarction whether or not treated with
             anti-platelet drugs.