Oxaliplatin, Fludarabine, Cytarabine and Rituximab in Richter's Syndrome, Refractory CLL and PLL
This study has been completed.
Sponsor:
M.D. Anderson Cancer Center
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
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Purpose
Primary Objectives:
- 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).
- 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.
- 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:
- Determine the duration of response, failure-free survival, and overall survival.
- 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.
- 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:
Drug: Fludarabine
30 mg/m^2 given IV for two days (Days 2 and 3).
Other Names:
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:
- 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.
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 May 16, 2013