Primary Objectives:

1. Determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of oxaliplatin in combination with fludarabine, Ara-C and rituximab in patients with Richter's transformation, prolymphocytic leukemia (PLL), or refractory/relapsed B-cell chronic lymphocytic leukemia (CLL).
2. Assess the complete response (CR) and partial response (PR) rate to combination therapy of oxaliplatin, fludarabine, Ara-C and rituximab in patients with Richter's transformation, PLL or refractory/relapsed B-cell CLL.
3. Determine the safety and toxicity profile of combination therapy of oxaliplatin, fludarabine, Ara-C and rituximab in patients with Richter's transformation, PLL or refractory/relapsed B-cell CLL.

Secondary Objectives:

1. Determine the duration of response, failure-free survival, and overall survival.
2. Determine the incidence of infections (bacterial, fungal, and viral) in patients with Richter's transformation, prolymphocytic leukemia or refractory/relapsed B-cell CLL treated with rituximab, oxaliplatin, fludarabine and Ara-C; monitor immune parameters such as T cell counts and immunoglobulin levels; and monitor Epstein-Barr virus (EBV) status.
3. Characterize the pharmacodynamics of oxaliplatin in leukemia cells with respect to total adduct formation, cross-link formation and excision deoxyribonucleic acid (DNA) responses. Compare these parameters in cells from the same patient after treatment with oxaliplatin in combination with fludarabine and Ara-C.

Oxaliplatin, fludarabine, cytarabine and rituximab are anticancer drugs. Oxaliplatin is a platinum compound that has been shown to be effective in fighting other cancers. Oxaliplatin is a third generation platinum compound with higher activity and less toxicity in colon cancer and other tumors compared to other platinum compounds, such as cisplatin. Oxaliplatin has shown activity in patients with relapsed or refractory non-Hodgkin's lymphoma.

Before treatment starts, you will have a complete physical exam and routine blood tests (about 2 teaspoons). A bone marrow sample will be collected. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle. Women who are able to have children must have a negative blood or urine pregnancy test.

This research study has two parts, a Phase I part and a Phase II part. You will receive at least 1 cycle of therapy.

Oxaliplatin will be given through a needle in your vein (called an IV) for 4 days (Days 1 through 4). Rituximab will be given through an IV on Day 3 of the first cycle and on Day 1 on every cycle after that. One day after the first dose of oxaliplatin and rituximab (Day 2), fludarabine and cytarabine will be given through an IV for two days (Days 2 and 3). Peg-filgrastim will be given subcutaneously (through a needle just under your skin) on Day 6. Other IV fluids such as saline will be given on all of the treatment days to keep you from being dehydrated, which means that the daily visit may take eight hours. The combination will be repeated once a cycle (every 28 days) for up to a total of 6 cycles.

During the Phase I and II phases of the study, researchers will be testing different dose levels of the study drug combination. Three patients will be enrolled at each dose level. Each time the dose level is raised, it will occur after each patient has been monitored for 28 days. Individual patients who do not experience serious drug-related side effects after the second cycle may receive the next higher dose level for the following treatment cycles.

Drugs will be given before each dose of rituximab to lower the risk of side effects. If side effects do occur during rituximab treatment, rituximab may have to be stopped until the side effects go away and then restarted. This may make your time in the outpatient area longer.

The first treatment cycle will be given at M. D. Anderson. Depending on your response to treatment, up to 5 more cycles can be performed either at M. D. Anderson or at home with your regular physician. After 3 cycles of treatment, you will be checked at M. D. Anderson to see if the disease is responding to treatment. If the disease is responding after 3 cycles of therapy, you may continue to receive therapy for up to 3 more cycles. If the disease is not responding, you will be taken off the study and your doctor will discuss other treatment options with you.

Once the best safe dose of the drug combination is found in the Phase I portion of the study, the next group of participants entering the study will take part in the Phase II portion of the study. The goal of this part of the study is to look at the effects of the drug combination in patients with refractory CLL, prolymphocytic leukemia or Richter's transformation. The dose level for the combination will be the one found in the Phase I part of the study.

The same dose levels for all four drugs will be used throughout the Phase II portion of the study, unless intolerable side effects occur. In that case, the dose may be lowered or the treatment may be stopped. You will be taken off study if the disease gets worse.

During each treatment cycle, you will have blood samples (about 1 teaspoon each) taken once every 1-2 weeks. Bone marrow biopsies will be done at the end of the 3rd and 6th chemotherapy cycles.

After your last cycle of treatment is completed, you will have blood drawn (about 2 teaspoons each) every 3 months for as long as you are in remission, for routine testing.

This is an investigational study. The FDA has authorized the use of these drugs for research only, when given for this purpose. All of these drugs are commercially available for other types of treatment. Oxaliplatin will be free of charge during the study. You and/or your insurance company will be responsible for the cost of the other drugs used in this study. Patients will be enrolled at M. D. Anderson, University of California, San Diego, or Dana-Farber Cancer Institute. Up to 52 patients will take part in this multicenter study. The estimated number of patients who will be treated at M. D. Anderson is up to 52.

Inclusion Criteria:

1. Histologically or cytologically confirmed Richter's transformation, fludarabine-refractory chronic lymphocytic leukemia or prolymphocytic leukemia.
2. Patients must be 18 years of age or older.
3. Patients must have a performance status of 0-2 (Zubrod scale).
4. Patients must have adequate renal function (serum creatinine below or equal to 2mg/dL or creatinine clearance greater than 30mL/min), unless renal dysfunction is considered due to organ infiltration by disease.
5. Patients must have adequate hepatic function (bilirubin less than or equal to 2.0 mg/dl; Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) less than or equal to 3 times the upper limit of normal (ULN) for the reference lab unless considered due to leukemia or congenital hemolytic disorder (for bilirubin).
6. Female patients of childbearing potential (including those <1 year post-menopausal) and male patients must agree to use contraception.
7. Patients must sign an informed consent indicating that they are aware of the investigational nature of this study in keeping with the policies of the hospital.
8. Patients must have platelet counts greater or equal to 20,000, unless due to disease involvement, or autoimmune disorders.

Exclusion Criteria:

1. Untreated or uncontrolled life-threatening infection.
2. Oxaliplatin, fludarabine, cytarabine or rituximab intolerance.
3. Pregnancy or lactation.
4. Chemotherapy and/or radiation therapy within 4 weeks.
5. Medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.

1 year, 9 months