Phase I Study of Continuous Infusion Schedule of FMdC in Hematologic Malignancies

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

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.

Study Overview

• Status: Completed
• Conditions: Hematologic Malignancies
• Intervention / Treatment: Drug: Tezacitabine (FMdC)

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description
Maximum tolerated dose (MTD)	MTD determination made from dose level without a dose-limiting toxicity (DLT)

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: Chiron Corporation
• Investigators: Principal Investigator: Stefan Faderl, MD, UT MD Anderson Cancer Center

Publications and helpful links

Helpful Links

• M.D. Anderson Cancer Center's website

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2001
• Primary Completion (Actual): February 12, 2004
• Study Completion (Actual): February 12, 2004

Study Registration Dates

• First Submitted: May 30, 2003
• First Submitted That Met QC Criteria: May 30, 2003
• First Posted (Estimate): June 2, 2003

Study Record Updates

• Last Update Posted (Actual): November 1, 2018
• Last Update Submitted That Met QC Criteria: October 31, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Chemotherapy; Hematologic Malignancies; Investigational; Nucleoside analogue
• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tezacitabine
• Other Study ID Numbers: ID01-168