Oxaliplatin, Fludarabine, Cytarabine and Rituximab in Richter's Syndrome, Refractory CLL and PLL

• Status: Completed
• Trial end date: 2011-01-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: Sanofi
• Treatments: Cytarabine; Fludarabine; Fludarabine phosphate; Oxaliplatin; Rituximab; Vidarabine

Criteria

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.