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

This study has been completed.
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00452374
First received: March 23, 2007
Last updated: October 25, 2011
Last verified: October 2011
  Purpose

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.

Condition Intervention Phase
Leukemia
Drug: Cytarabine
Drug: Fludarabine
Drug: Oxaliplatin
Drug: Rituximab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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 Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) Oxaliplatin [ Time Frame: From treatment onset to end of each cycle of treatment (every 21 days) ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 48
Study Start Date: November 2004
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oxaliplatin, Fludarabine, Cytarabine + Rituximab
Starting dose oxaliplatin 17.5mg/m^2/day intravenous (IV) for 4 days; Fludarabine 30 mg/m^2 IV and Cytarabine 1 g/m^2 IV for two days, + Rituximab 375 mg/m^2 IV on Day 3, Cycle 1 then Day 1 following cycles.
Drug: Cytarabine
1 g/m^2 given IV for two days (Days 2 and 3).
Other Names:
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine arabinosine hydrochloride
Drug: Fludarabine
30 mg/m^2 given IV for two days (Days 2 and 3).
Other Names:
  • Fludara
  • Fludarabine Phosphate
Drug: Oxaliplatin
Starting dose of 17.5 mg/m^2 IV for 4 days (Days 1 through 4).
Other Name: Eloxatin
Drug: Rituximab
375 mg/m^2 IV on Day 3 of the first cycle over 4-6 hours and on Day 1 on every cycle following.
Other Name: Rituxan

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00452374

Locations
United States, California
University of California-San Diego
La Jolla, California, United States, 92093
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
M.D. Anderson Cancer Center
Sanofi
Investigators
Principal Investigator: William G. Wierda, MD, PhD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00452374     History of Changes
Other Study ID Numbers: 2004-0373
Study First Received: March 23, 2007
Results First Received: July 28, 2011
Last Updated: October 25, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
B-cell chronic lymphocytic leukemia
Chronic Lymphocytic Leukemia
CLL
Prolymphocytic Leukemia
PLL
Richter's Transformation
High-grade non-Hodgkin's lymphoma
Hodgkin's disease
Acute leukemia
Small lymphocytic lymphoma
Oxaliplatin
Eloxatin
Fludarabine
Cytarabine
Ara-C
Cytosar
DepoCyt
Cytosine arabinosine hydrochloride
Rituximab
Rituxan

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Prolymphocytic
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cytarabine
Fludarabine monophosphate
Vidarabine
Fludarabine
Oxaliplatin
Rituximab
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on April 20, 2014