Oxaliplatin, Fludarabine, Cytarabine and Rituximab in Richter's Syndrome, Refractory CLL and PLL - Full Text View

Sponsors and Collaborators:	M.D. Anderson Cancer Center Sanofi-Aventis
Information provided by:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00452374

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 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 I Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
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:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Cytarabine hydrochloride Fludarabine Oxaliplatin Fludarabine monophosphate Rituximab Cytarabine

U.S. FDA Resources

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

Primary Outcome Measures:

Maximum tolerated dose (MTD) [ Time Frame: After each cycle of treatment (every 21 days) ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	52
Study Start Date:	November 2004
Estimated Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Phase I: Experimental Phase I: Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) Phase II: Effects of drug combination for dose level found in Phase I.	Drug: Cytarabine 1 g/m^2 given IV for two days (Days 2 and 3). Drug: Fludarabine 30 30 mg/m^2 given IV for two days (Days 2 and 3). Drug: Oxaliplatin Starting dose of 17.5 mg/m^2 IV for 4 days (Days 1 through 4). 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.

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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; SGOT or SGPT less than or equal to 3 X the 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-Aventis

Investigators

Principal Investigator:

William G. Wierda, MD, PhD

U.T.M.D. Anderson Cancer Center

More Information

Additional Information:

UT MD Anderson Cancer Center website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	UT MD Anderson Cancer Center ( William G. Wierda, MD / Professor )
Study ID Numbers:	2004-0373
Study First Received:	March 23, 2007
Last Updated:	August 3, 2009
ClinicalTrials.gov Identifier:	NCT00452374 History of Changes
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

Study placed in the following topic categories:

Richter Syndrome
Antimetabolites
Anti-Infective Agents
Leukemia, Lymphoid
Immunologic Factors
Lymphoma, Small Cleaved-cell, Diffuse
Leukemia
Oxaliplatin
Leukemia, Prolymphocytic
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, B-cell, Chronic
Hodgkin Disease
Lymphoma
Cytarabine
Immunoproliferative Disorders

Prolymphocytic Leukemia
Hodgkin Lymphoma, Adult
Rituximab
Hodgkin's Disease
Fludarabine monophosphate
Immunosuppressive Agents
Antiviral Agents
Lymphatic Diseases
Chronic Lymphocytic Leukemia
Fludarabine
Antirheumatic Agents
Lymphoproliferative Disorders
Leukemia, B-Cell
Lymphoma, Non-Hodgkin

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Leukemia, Lymphoid
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Leukemia
Oxaliplatin
Leukemia, Prolymphocytic
Leukemia, Lymphocytic, Chronic, B-Cell
Therapeutic Uses
Cytarabine

Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Rituximab
Fludarabine monophosphate
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Lymphatic Diseases
Neoplasms
Fludarabine
Antirheumatic Agents
Lymphoproliferative Disorders
Leukemia, B-Cell

ClinicalTrials.gov processed this record on September 10, 2009