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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I-II Study of Oxaliplatin, Fludarabine, Cytarabine and Rituximab in Patients With Richter's Transformation, Prolymphocytic Leukemia or Refractory/Relapsed B-Cell C

Brief 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.

Detailed Summary:

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 diffe
Sponsor: M.D. Anderson Cancer Center

Current Primary Outcome: Maximum Tolerated Dose (MTD) Oxaliplatin [ Time Frame: From treatment onset to end of each cycle of treatment (every 21 days) ]

MTD defined as dose level at which 2/3 or 2/6 participants experience Dose Limiting Toxicity (DLT), where DLTs are any oxaliplatin-related ≥Grade 3 non-hematological toxicity involving a major organ system (brain, heart, kidney, liver, lung) in the National Cancer Institute (NCI) Version 3.0 toxicity scale.


Original Primary Outcome:

Current Secondary Outcome: Number of Participants With a Complete Response or Partial Response [ Time Frame: Evaluation every 3 cycles of treatment (28 days per cycle), approximately 90 days ]

According to International Workshop Response Criteria for Non-Hodgkin's Lymphomas: Complete remission (CR) defined as > 30% lymphocytes in the bone marrow, recovery of blood counts and no clinical symptoms; and Partial remission (PR) defined as > 50% decrease of clinical symptoms from baseline and recovery from blood counts.


Original Secondary Outcome:

Information By: M.D. Anderson Cancer Center

Dates:
Date Received: March 23, 2007
Date Started: November 2004
Date Completion:
Last Updated: October 25, 2011
Last Verified: October 2011