Lenalidomide Plus Rituximab for Indolent Non-Hodgkin's Lymphoma

The goal of this clinical research study is to learn if lenalidomide in combination with rituximab in previously untreated indolent non-Hodgkin's lymphoma can control the disease. The safety of this combination will also be studied.

The Study Drugs:

Rituximab is a type of drug known as a monoclonal antibody. It is designed to act against the CD20 antigen that is found on the surface of both normal B lymphocytes or on the malignant lymphoma cells. When rituximab attacks the CD20 antigen, it may kill the lymphoma cells.

Lenalidomide is designed to change the body's immune system. It 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.

If you are found to be eligible to take part in this study, you will take lenalidomide by mouth on Days 1-21 of each 28-day study cycle in schedule "A", or on Days 2-22 of schedule "B". You should 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).

Lenalidomide is being provided to you under a special distribution program called RevAssist®. A company called Biologics will directly mail you your supply of lenalidomide to your home. The RevAssist® toll-free contact number for patients is 1-888-423-5436. You should contact that number in order to ask for information on how to properly dispose of any unused supply of lenalidomide by shipping the drug back.

You will receive rituximab through a needle in your vein on Day 1 (Schedule A) or on Days 1, 8, 15, and 22 of Cycle 1 (Schedule B) over 4-8 hours. You will receive rituximab on Day 1 of all subsequent cycles.

You will be given a diary to record when you take all of the study drugs and any problems or illnesses you may experience. You should also write down in the diary any other drugs you take while you are on this study.

Study Visits:

After you begin your treatment, you will have study visits at the beginning of each cycle. If your doctor thinks it is necessary, the check-up visits may take place more often.

At these visits, the following tests and procedure will be performed:

• You will have a complete physical exam, including measurement of vital signs.
• You will be asked questions about how you have felt since your last visit.
• You will be asked about any drugs you have taken since your last visit.
• You should bring the diary you were given earlier to each visit.
• Blood (about 8 tablespoons) will be drawn for routine blood tests and to check on the status of the disease.

On Days 8 and 22 of Cycle 1, blood (about 2 tablespoons) will be drawn for routine tests.

On Day 14 of Cycles 2-12, blood (about 2 tablespoons) will be drawn for routine tests.

At the end of each 28-day treatment cycles, you will have a visit with the study doctor to see if it is safe for you to continue on this study and make sure the cancer has not gotten worse. At this visit, blood (about 8 tablespoons) will be drawn for routine blood tests to check on the status of the disease.

If your doctor thinks it is necessary, at any of the study visits you may have a bone marrow biopsy/aspirate, x-rays, CT scans, positron emission tomography (PET) scans, or gastrointestinal endoscopy to check the status of the disease.

Pregnancy Tests:

Women who are able to become pregnant with regular or no menstrual cycles must agree to have pregnancy tests weekly for the first 28 days of study and then every 28 days while on study, at the end-of-study visit, and at Day 28 following discontinuation from the study.

Women with irregular menstrual cycles must have pregnancy tests weekly for the first 28 days, then every 14 days while on study, at the end-of-study visit, and at days 14 and 28 following discontinuation from the study.

Length of Study:

You may continue to take the study drugs for up to 12 cycles. You will be taken off study earl if the disease gets worse or you experience intolerable side effects.

End-of-Study Visit:

Once you are off-study, you will have an end-of-study visit. At this visit, the following tests and procedures will be performed:

• You will have a complete physical exam, including measurement of vital signs and weight.
• You will be asked questions about how you have felt since your last visit.
• You will be asked about any drugs you have taken since your last visit.
• Blood (around 3 tablespoons) will be drawn for routine blood tests to check on the status of the disease.
• You will have bone marrow biopsy/aspirate to check the status of disease.
• You will have x-rays or CT scans to check the status of the disease.
• You should return any unused lenalidomide capsules.

Long-Term Follow-Up:

After the end-of-study visit, you will be contacted by phone every 6 months from then on to check on your health and for information about any other cancer treatments you may have received.

You will have CT scans of your neck, thorax, abdomen and pelvis every 3 months for 1 year, every 6 months for the following year, and then 1 time a year after that.

This is an investigational study. Lenalidomide is FDA approved and commercially available for multiple myeloma and myelodysplastic syndrome. Its use in patients with indolent non-Hodgkin's lymphoma is investigational.

Rituximab is FDA approved and commercially available for the treatment of non-Hodgkin's lymphomas, including indolent non-Hodgkin's lymphoma.

Up to 155 participants with take part in this study. All will be enrolled at MD Anderson.

• Drug: Lenalidomide

  20 mg by mouth (PO) daily on days 1 - 21 followed by 7 days rest (28 day cycle). Following cycle 3, if patients fail to show a response (partial or complete) the dose will be increased to 25mg/day.

  Schedule B: Lenalidomide will be administered orally at 20 mg total daily dose on days 2 to 22 of a 28 day cycle in patients with follicular lymphoma. Following cycle 3, if patients fail to show a response (partial or complete) the dose will be increased to 25mg/day. Patients with a diagnosis of small lymphocytic lymphoma (SLL) will begin at a dose of 10 mg total daily on days 2 to 22 of a 28 day cycle. This dose will be escalated by 5mg every 28 days up to 20mg if no toxicity is encountered. If no response is observed by cycle 3, the dose will be increased to 25 mg.

  Other Names:

  • Revlimid
  • CC-5013
• Drug: Rituximab
  375 mg/m^2 by vein over 4-8 Hours on day 1 of cycles 1-12 in schedule A, and day 1, 8,15, and 22 of cycle 1 and on day 1 of every subsequent cycle in schedule B.
  Other Name: Rituxan

Inclusion Criteria:

1. Understand and voluntarily sign an informed consent form.
2. Age >/= 18 at the time of signing the informed consent form.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Untreated indolent non-Hodgkin's lymphoma stage III-IV including small lymphocytic lymphoma, marginal zone lymphoma, grade 1 or 2 follicular lymphoma. (prior radiation for localized disease allowed).
5. At least one measurable lesion according to the International workshop standardized response criteria for non-Hodgkin's lymphomas (IWG) greater than 1.5cm.
6. ECOG performance status of </= 2 at study entry.
7. Laboratory test results within these ranges: Absolute neutrophil count >/= 1.5 x 10^9/L; Platelet count >/=100 x 10^9/L; Serum creatinine </= 2.0 mg/dL; Total bilirubin </=1.5 mg/dL; AST (SGOT) and ALT (SGPT) </=2 x ULN or </=5 x ULN if hepatic metastases are present.
8. Disease free of prior malignancies for >/= 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast, or localized prostate cancer treated with curative intent.
9. All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
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 prescribing 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 4 weeks before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing.
11. Men must agree to use a latex condom during sexual contact with a female of child bearing potential even if they have had a successful vasectomy.
12. For patients with bulky disease (tumors >5cm) must be able to take aspirin (81 mg or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin.

Exclusion Criteria:

1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
2. Pregnant or breast feeding females.
3. 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.
4. Use of any chemotherapy or experimental therapy within 28 days of enrollment.
5. Known hypersensitivity to thalidomide.
6. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
7. Any prior use of lenalidomide.
8. Concurrent use of other anti-cancer agents or experimental treatments.
9. Known positive for HIV or infectious hepatitis type B or C. (Hepatitis B core antibody can be positive if Hep B surface antigen is negative and no HBV DNA in blood, indicating a cleared infection.)