Clinical Trial: Oxaliplatin, Fludarabine, Cytarabine, and Rituximab in Patients With Richter's Transformation and Leukemias

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, Aggressive, Relapsed or Refra

Brief Summary: The goal of this clinical research study is to find the highest tolerable dose of fludarabine and cytarabine that can be given in combination with oxaliplatin and rituximab in the treatment of chronic lymphocytic leukemia (CLL), prolymphocytic leukemia, or Richter's transformation. Once the highest tolerable dose for this drug combination is found, the next goal of the study will be to find out if this combination therapy is effective in shrinking or slowing the growth of these diseases.

Detailed Summary:

Cytarabine is designed to insert itself into DNA (the genetic material of cells) and stop the DNA from repairing itself.

Oxaliplatin is designed to kill cancer cells by damaging their DNA.

Fludarabine is designed to make cancer cells less able to repair damaged DNA. This may increase the likelihood of the cells dying.

Rituximab is designed to attach to lymphoma cells, which may cause them to die.

During the Phase I portion of the study, researchers will be testing different doses of the study drug combination. Oxaliplatin and rituximab will be given at the same dose level. However, fludarabine and cytarabine will be given daily for 2 days to the first 3 participants, daily for 3 days to the next 3 participants, and daily for 4 days to the next 3 participants. Although the plan is to treat 3, up to 6 participants may be treated in each of these groups.

If participants who receive the fludarabine and cytarabine for 2 or 3 days do not experience intolerable side effects, after the second cycle they may receive the next higher dose (an additional day of fludarabine and cytarabine) for the following cycles.

Once the highest tolerated dose of fludarabine and cytarabine given in combination with oxaliplatin and rituximab is found, the next group of participants entering the study will take part in the Phase II portion of the study. Participants in the Phase II portion will receive the study drugs at the highest tolerated dose found in the Phase I portion of the study. The goal of this part of the study is to look at how effective the drug combination is in treating patients with Richter's syndrome, prolymphocytic leukemia, and aggres
Sponsor: M.D. Anderson Cancer Center

Current Primary Outcome: Maximum Total Tolerated Dose (MTD) of Daily Combination Fludarabine 30 mg/m^2 and Cytarabine 500 mg/m^2 Among 3 Dose Levels (Dose Level 1: 2 Days, Dose Level 2: 3 Days or Dose Level 3: 4 Days) [ Time Frame: Up to 36 weeks (6 cycles each 4-6 weeks) ]

Maximum dose levels for Phase I determined among three possible dose levels of Fludarabine and Cytarabine in combination with fixed doses of Oxaliplatin and Rituximab. Fludarabine and Cytarabine Dose Level 1: Days 2-3 (2 Days); Dose Level 2: Days 2-4 (3 Days); and Dose 3: Days 2-5 (4 Days). MTD is dose level at which less than 2/3 or 2/6 participants experience dose limiting toxicities (DLTs). The number of days of fludarabine and cytarabine administration increased simultaneously. Participants received a subsequent cycle of treatment with 1 additional day of fludarabine and cytarabine treatment no less than 4 weeks from the initiation of the previous cycle if no drug-related grade 3 or 4 non-hematologic life-threatening adverse events, and drug-related non-hematologic toxicity resolved to baseline or < grade 2. A maximum of 6 cycles were administered.


Original Primary Outcome: Phase 1: Determine maximum total tolerated dose of fludarabine & cytarabine in combination with oxaliplatin & rituximab. Phase 2: Assess objective response rates, including complete & partial response rates, & define safety/toxicity profile of OFAR.

Current Secondary Outcome: Overall Response: Number of Participants With Complete Remission, Nodular Partial Remission, and Partial Remission [ Time Frame: Up to 36 weeks (6 cycles each 4-6 weeks) ]

Overall Response includes Complete remission (CR), nodular partial remission (nPR), and partial remission (PR) in high-risk, previously untreated participants with Chronic Lymphocytic Leukemia treated with CFAR using National Cancer Institute - Working Group response criteria. CR defined as zero nodes, Liver/spleen not palpable, zero symptoms, polymorphonuclear leukocyte (PMN)>1,500/uL, Platelets >100,000uL, Hemoglobin (untransfused) >11.0g/dL, Lymphocytes <4,000/uL and Bone Marrow Aspirate biopsy <30% lymphocytes with no lymphocyte infiltrate; PR defined as nodes >/= 50% decrease,Liver/spleen >/= 50% decrease, symptoms not applicable, PMN >1,500/uL or >50% improvement from baseline, Platelets 100,000uL or >/=50% decrease improvement from baseline, Hemoglobin (untransfused) >11.0g/dL or >50% improvement from baseline, Lymphocytes >50% decrease and Bone Marrow Aspirate biopsy Not Applicable for PR; with nPR defined same as PR but with <30% lymphocytes with residual disease on biopsy.


Original Secondary Outcome: (a) To determine the duration of response, disease-free survival, and overall survival (b) To determine the pharmacokinetics and pharmacodynamics of oxaliplatin administered alone and following infusion of fludarabine and cytarabine.

Information By: M.D. Anderson Cancer Center

Dates:
Date Received: May 11, 2007
Date Started: May 2007
Date Completion:
Last Updated: November 1, 2013
Last Verified: November 2013