Phase I Study of Continuous Infusion Schedule of FMdC in Hematologic Malignancies - Full Text View

Sponsor:	M.D. Anderson Cancer Center
Collaborator:	Chiron Corporation
Information provided by:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00061620

Purpose

The goal of this clinical research study is to find the highest dose of Tezacitabine (FMdC) which can be safely given as a continuous infusion by vein to patients with hematologic malignancies. The general safety and effectiveness of this drug will also be studied.

Condition	Intervention	Phase
Hematologic Malignancies	Drug: Tezacitabine (FMdC)	Phase I

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:	Phase I Study of Continuous Infusion Schedule of (E)-2'-Deoxy-2'-(Fluoromethylene) Cytidine (Tezacitabine, FMdC) in Hematologic Malignancies

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: MDL 101731 Tezacitabine

U.S. FDA Resources

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

Primary Outcome Measures:

Maximum tolerated dose (MTD) [ Designated as safety issue: Yes ]
MTD determination made from dose level without a dose-limiting toxicity (DLT)

Enrollment:	19
Study Start Date:	September 2001
Study Completion Date:	February 2004
Primary Completion Date:	February 2004 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Tezacitabine Tezacitabine as a bolus infusion daily x 5	Drug: Tezacitabine (FMdC) 7.5 mg/m2 bolus infusion daily x 5 Other Names: FMdC (E)-2'-Deoxy-2'-(Fluoromethylene) Cytidine

Detailed Description:

Patients with leukemias that have relapsed from previous therapies have a low cure rate. Hence the need to discover new antileukemic agents. Tezacitabine is a nucleoside analogue with equivalent or even superior activity when compared with ara-C in leukemic cell lines. It has shown significant antitumor activity in vitro and in vivo tumor models. Several phase I studies with various dosing schedules have been conducted in solid tumors where the dose-limiting toxicity (DLT) is mainly myelosuppression, usually a favorable feature for development of leukemia. In a phase I study in hematological malignancies, we used Tezacitabine as a bolus infusion daily x 5. The DLT consisted of grade 3 CNS toxicities and mucositis in 3/6 patients. The study is ongoing and we are currently evaluating a dose level of 7.5 mg/m2 as possible Maximum Tolerated Dose (MTD). However, in view of the fact that tezacitabine is a cell cycle specific agent with a short terminal plasma half-life of 2 to 6 hours, a continuous infusion dosing schedule may enhance the activity and reduce the incidence of adverse effects of tezacitabine.

Eligibility

Ages Eligible for Study:	15 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Patient with relapsed/refractory acute leukemias (AML, ALL, high-grade myelodysplastic syndromes, CMML in transformation with >/= 10% peripheral blood/bone marrow blasts, CML in blast crisis), or patients with relapsed/refractory CLL and an absolute neutrophil count of >/= 1,000/ml and platelet count of >/= 75,000/ml.
Signed informed consent indicating that patients are aware of the investigational nature of this study, and in keeping with the policies of this hospital. The only acceptable consent form is attached at the end of this protocol.
Age >/= 15 years.
ECOG performance status </= 2.
No severe, concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for study entry.
Pregnant and/or lactating females are not eligible.
Normal organ function (serum bilirubin £ 2 mg/dL, serum creatinine £ 2 mg/dL). Patients with renal or liver dysfunction due to organ leukemic involvement may be eligible after discussion with the principle investigator.
Patients must be off of all previous chemotherapy, immunotherapy, or radiotherapy for at least 2 weeks prior to entering this study, and must have recovered from all toxic effects, unless life-threatening increases in tumor burden occur.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00061620

Locations

United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Chiron Corporation

Investigators

Principal Investigator:

Stefan Faderl, MD

UT MD Anderson Cancer Center

More Information

Additional Information:

M.D. Anderson Cancer Center's website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Stefan H. Faderl, MD/ Associate Professor, UT MD Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00061620 History of Changes
Other Study ID Numbers:	ID01-168
Study First Received:	May 30, 2003
Last Updated:	October 22, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:

Investigational
Chemotherapy
Hematologic Malignancies
Nucleoside analogue

Additional relevant MeSH terms:

Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases
2'-deoxy-2'-(fluoromethylene)cytidine
Enzyme Inhibitors

Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 12, 2012