Lenalidomide as Initial Treatment of Patients With Chronic Lymphocytic Leukemia (CLL) Age 65 and Older

A Phase II Study of Lenalidomide as Initial Treatment of Patients With Chronic Lymphocytic Leukemia Age 65 or Older.

Primary Objective:

• To assess the activity of lenalidomide in patients with previously untreated chronic lymphocytic leukemia (CLL) age 65 and older.

Secondary Objective:

• To assess the tolerability of lenalidomide in patients with untreated CLL age 65 and older

The Study Drug:

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 or prevent the growth of cancer cells.

Drug Administration:

If you are found to be eligible to take part in this study, you will take lenalidomide by mouth every morning at about the same time each day for 28 days. Twenty-eight (28) days is considered 1 cycle. The dose and schedule of lenalidomide may be adjusted up or down, depending on how the disease responds and the side effects you may experience. Swallow lenalidomide capsules whole with 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 taking your dose for the entire day, take your regular dose the next scheduled day (do NOT take double your regular dose to make up for the missed dose).

Concomitant Medications:

Allopurinol will be prescribed for you during the first 14 days of treatment. This medication is taken by mouth and will help protect your kidney function.

Study Visits:

During this study, you will have blood (about 1 tablespoon each) drawn every other week until the best dose of lenalidomide has been found. Blood tests (about 1 tablespoon each) may be done more often if the dose of medication needs to be changed or if you experience intolerable side effects. Women who are able to have children must have a negative urine or blood (less than 1 teaspoon) pregnancy test 10 - 14 days and 24 hours before starting lenalidomide therapy, even if they have not had a menstrual period due to treatment of the disease or had as little as one menstrual period in the past 24 months. If you have regular or no menstrual cycles, you will then have pregnancy tests every week for the first 4 weeks, then every 4 weeks while taking lenalidomide, again when 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 pregnancy tests every week for the first 4 weeks, then every 2 weeks while taking lenalidomide, again when you have been taken off of lenalidomide therapy, and then 14 days and 28 days after you have stopped taking lenalidomide. Every month for the first 3 months, then at Months 6, 9, 12, and 15 you will have a physical exam to see how you are doing. After the 15-month visit, you will have a physical exam every 6 months.

After the first 3 months, and then every 6 months after that (unless your study doctor does not think it is necessary), you will have a bone marrow biopsy and aspirate performed to check the status of the disease.

Length of Study:

You may stay on this study for as long as you are benefitting. You will be taken off this study early if the disease gets worse or intolerable side effects occur.

This is an investigational study. Lenalidomide is FDA approved and commercially available. Lenalidomide is approved for the treatment of patients with transfusion-dependent anemia due to Low- or Intermediate-1-risk myelodysplastic syndromes associated with the chromosome 5 abnormality with or without other chromosome abnormalities. Lenalidomide is also approved in combination with dexamethasone for the treatment of patients with multiple myeloma that have received at least one prior therapy. Its use in this study, for this disease, 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 untreated CLL or small lymphocytic lymphoma (SLL) with indication to treatment according to NCI Working Group guidelines.Patients that have received single agent rituximab will be allowed to participate in this study.
2. Age 65 or older
3. Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance status of 0-2.
4. Adequate renal function indicated by serum creatinine less or equal to 2 and adequate hepatic function indicated as total bilirubin less or equal to upper level of normal and as alanine aminotransferase (ALT) less or equal 2 upper limit of normal (ULN).
5. Able to understand and sign Informed Consent after the investigational nature, study design, risks and benefits have been explained.
6. Able to adhere to the study visit schedule and other protocol requirements.
7. Disease free of prior malignancies for 5 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 can be enrolled in the study as long as they have a reasonable expectation to have been cured with treatment modality received.
8. Females of childbearing potential (FCBP). 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). 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 lenalidomide and must either commit to continued abstinence
9. Continued from above. 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 4 weeks before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing.
10. Men must agree to use a condom during sexual contact with a female of child bearing potential even if they have had a successful vasectomy.
11. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
12. All patients must be able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to Acetylsalicylic Acid (ASA) may use warfarin or low molecular weight heparin.

Exclusion Criteria:

1. Known sensitivity to thalidomide or its derivatives.
2. Documented prolymphocytic leukemia (prolymphocytes more than 55% in the blood).
3. Known positivity for HIV or active hepatitis (B or C).
4. A serious medical condition, laboratory abnormality or psychiatric illness that would interfere with the ability of the patient to participate in this program according to the judgement of the Principal Investigator.
5. Active cardiovascular disease as defined by the New York Heart Association Class 3 or 4.
6. History of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
7. Concurrent use of other chemotherapy agents.
8. Pregnant or breast feeding females. Lactating females must agree not to breast feed while taking lenalidomide.
9. No known history of tuberculosis or recent exposure to tuberculosis.