Lenalidomide and Rituximab as Treatment of Chronic Lymphocytic Leukemia
Lenalidomide and Rituximab as Treatment of Chronic Lymphocytic Leukemia
The goal of this clinical research study is to learn if the combination of lenalidomide and
 rituximab can help to control Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic
 Lymphoma (SLL) in patients who have already received therapy. The safety of this drug
 combination will also be studied.
The Study Drugs:

 Lenalidomide is designed to change the body's immune system and may also interfere with the
 development of tiny blood vessels that help support tumor growth. Therefore, in theory, it
 may decrease the growth of cancer cells.

 Rituximab is designed to bind to a protein, called cluster of differentiation antigen 20
 (CD20), that is on the surface of the leukemia cells, allowing the leukemia cells to be
 destroyed by the immune system.

 Drug Administration:

 If you are found to be eligible to take part in this study, you will receive rituximab
 through a needle into your vein 1 time a week in Cycle 1. You will not receive rituximab
 during Cycle 2, but you will continue to take lenalidomide.You will receive a dose of
 rituximab by vein on Day 1 of Cycles 3-12. Your first dose of rituximab will be given over
 6-8 hours. If the first dose is well tolerated, you may receive the next doses over 2-4
 hours. If the doctor thinks it is needed, the next doses may given over a longer time.

 On Day 9 of Cycle 1, you will begin taking lenalidomide by mouth once a day. You will then
 take lenalidomide once a day, every day.

 The dose and schedule of lenalidomide may change depending on the side effects you may
 experience. You should swallow lenalidomide capsules whole with a glass (8 ounces) water at
 the same time each day. Do not break, chew, or open the capsules. If you miss a dose of
 lenalidomide, take it as soon as you remember on the same day. If you miss a dose, it should
 NOT be made up on another day.

 Each study cycle is 4 weeks.

 Study Visits:

 Once a week during the first 5 weeks, blood (about 1 tablespoon) will be drawn for routine
 tests.

 After the first 5 weeks, blood (about 1 tablespoon) will be drawn for routine tests every 2
 weeks until the doctor thinks your dose of lenalidomide will not change. After this, blood
 (about 1 tablespoon) will then be drawn every 4 weeks for routine tests.

 At the end of Cycles 3, 6, and 12, you will have a bone marrow biopsy and aspirate to check
 the status of the disease. Blood (about 1 tablespoon) will be drawn for routine blood tests.

 If you stay on study past 12 cycles, once every 6 cycles (Cycles 18, 24, 30, and so on), you
 will have a bone marrow biopsy and aspirate to check the status of the disease. Blood (about
 1 tablespoon) will be drawn for routine blood tests.

 Blood (about 1 tablespoon) will be drawn more often if the dose of lenalidomide needs to be
 changed or if you experience intolerable side effects.

 Pregnancy Testing:

 Women who are able to become pregnant must have a negative urine or blood (less than 1
 teaspoon) pregnancy test 10-14 days and 24 hours before the first dose of lenalidomide, even
 if they have not had a menstrual period due to treatment of the disease or had only 1
 menstrual period in the past 24 months.

 If you have regular or no menstrual cycles, you will then have a urine or blood (less than 1
 teaspoon) pregnancy test every week for the first 4 weeks, then every 4 weeks while taking
 lenalidomide, again as soon as you have been taken off of lenalidomide therapy, and then 28
 days after you have stopped taking lenalidomide.

 If you have irregular menstrual cycles, you will have urine or blood (less than 1 teaspoon)
 pregnancy test every week for the first 4 weeks, then every 2 weeks while taking
 lenalidomide, again as soon as you have been taken off of lenalidomide therapy, and then at
 14 days and 28 days after you have stopped taking lenalidomide.

 Length of Study:

 You will be on study treatment for about 1 year. You will be taken off study early if you
 experience intolerable side effects or the disease gets worse.

 If the doctor thinks you are benefiting, you may be able to continue taking the study
 treatment. If you continue, you will follow the same schedule of dosing and study visit
 schedule.

 This is an investigational study. Lenalidomide and rituximab are FDA approved and
 commercially available. Lenalidomide is approved for the treatment of multiple myeloma and
 some myelodysplastic syndromes. Rituximab is approved for the treatment of chronic
 lymphoproliferative disorders and non-Hodgkin's lymphoma. The combination of these drugs to
 treat CLL and SLL is investigational.

 Up to 60 patients will take part in this study. All will be enrolled at M. D. Anderson.
Inclusion Criteria:

 1. Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)
 with active disease.

 2. Patients must be age 18 or over at the signing of consent and must understand and
 voluntarily sign an informed consent.

 3. Prior treatment with purine analog based chemotherapy or chemoimmunotherapy.

 4. Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance
 status of 0-2.

 5. Adequate renal function indicated by serum creatinine less or equal to 2 mg/dl.
 Adequate hepatic function indicated as total bilirubin less or equal to 2 mg/dl and
 ALT less or equal to two times the upper limit of normal.

 6. Disease free of prior malignancies for 3 years with exception of currently treated
 basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix
 or breast. Patients with malignancies with indolent behavior such as prostate cancer
 treated with radiation or surgery can be enrolled in the study as long as they have a
 reasonable expectation to have been cured with the treatment modality received.

 7. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
 test (sensitivity of at least 50 milli-International unit (mIU/mL) 10-14 days prior to
 starting lenalidomide. A female of childbearing potential is a sexually mature woman
 who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been
 naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at
 any time in the preceding 24 consecutive months).

 8. Continued from Criteria #7. 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 talking lenalidomide. FCBP must also agree to ongoing pregnancy
 testing.

 9. Continued from Criteria #8: 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.

 10. Men must agree not to father a child. They must agree to use a latex condom during
 sexual contact with females of childbearing potential while participating in the study
 and for at least 28 days following discontinuation from the study even if he has
 undergone a vasectomy. They will be warned that sharing study drug is prohibited and
 will be counseled about pregnancy precautions and potential risks of fetal exposure.
 They must agree to abstain from donating blood, semen, or sperm during study
 participation and for at least 28 days after discontinuation from the study.

 11. Continued from Criteria #10: Counseling about the requirement for latex condom use
 during sexual contact with females of childbearing potential and the potential risks
 of fetal exposure must be conducted at a minimum of every 28 days. During counseling,
 subjects must be reminded not to share study drug and to not donate blood, sperm, or
 semen (during study participation and for 28 days following discontinuation from the
 study).

 Exclusion Criteria:

 1. Known sensitivity to lenalidomide or other thalidomide derivatives or rituximab.

 2. Documented prolymphocytic leukemia (prolymphocytes more than 55% in the blood).

 3. Known positivity for HIV or active hepatitis (B or C).

 4. Pregnant or breast feeding females.

 5. History of tuberculosis treated within the last five years or recent exposure to
 tuberculosis.

 6. Any serious medical condition, laboratory abnormality, or psychiatric illness that
 places the subject at unacceptable risk if he/she were to participate in the study.

 7. Patients with a recent history of deep vein thrombosis (DVT) or pulmonary embolus
 (PE), in the six months prior to enrollment are not eligible for this study.