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Phase 2 N=48 Treatment

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

Leukemia

Enrolled (actual)
48
Serious AEs
58.3%
Results posted
Aug 2011
Primary outcome: Primary: Maximum Tolerated Dose (MTD) Oxaliplatin — 25 mg/m^2

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
Cytarabine (Drug); Fludarabine (Drug); Oxaliplatin (Drug); Rituximab (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
M.D. Anderson Cancer Center
Primary completion
Jan 2011

Outcome Measures

OutcomeResultp-value
PRIMARY
Maximum Tolerated Dose (MTD) Oxaliplatin
25
SECONDARY
Number of Participants With a Complete Response or Partial Response
12; 28

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.

Eligibility Criteria

Inclusion Criteria

  • Histologically or cytologically confirmed Richter's transformation, fludarabine-refractory chronic lymphocytic leukemia or prolymphocytic leukemia.
  • Patients must be 18 years of age or older.
  • Patients must have a performance status of 0-2 (Zubrod scale).
  • 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.
  • 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).
  • Female patients of childbearing potential (including those <1 year post-menopausal) and male patients must agree to use contraception.
  • 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.
  • Patients must have platelet counts greater or equal to 20,000, unless due to disease involvement, or autoimmune disorders.

Exclusion Criteria

  • Untreated or uncontrolled life-threatening infection.
  • Oxaliplatin, fludarabine, cytarabine or rituximab intolerance.
  • Pregnancy or lactation.
  • Chemotherapy and/or radiation therapy within 4 weeks.
  • 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.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00452374). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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