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

Primary Purpose

Hematologic Malignancies

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Tezacitabine (FMdC)
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematologic Malignancies focused on measuring Investigational, Chemotherapy, Hematologic Malignancies, Nucleoside analogue

Eligibility Criteria

15 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • UT MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tezacitabine

Arm Description

Tezacitabine as a bolus infusion daily x 5

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
May 30, 2003
Last Updated
October 31, 2018
Sponsor
M.D. Anderson Cancer Center
Collaborators
Chiron Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT00061620
Brief Title
Phase I Study of Continuous Infusion Schedule of FMdC in Hematologic Malignancies
Official Title
Phase I Study of Continuous Infusion Schedule of (E)-2'-Deoxy-2'-(Fluoromethylene) Cytidine (Tezacitabine, FMdC) in Hematologic Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
September 6, 2001 (Actual)
Primary Completion Date
February 12, 2004 (Actual)
Study Completion Date
February 12, 2004 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
Chiron Corporation

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematologic Malignancies
Keywords
Investigational, Chemotherapy, Hematologic Malignancies, Nucleoside analogue

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tezacitabine
Arm Type
Experimental
Arm Description
Tezacitabine as a bolus infusion daily x 5
Intervention Type
Drug
Intervention Name(s)
Tezacitabine (FMdC)
Other Intervention Name(s)
FMdC, (E)-2'-Deoxy-2'-(Fluoromethylene) Cytidine
Intervention Description
7.5 mg/m2 bolus infusion daily x 5
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD)
Description
MTD determination made from dose level without a dose-limiting toxicity (DLT)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stefan Faderl, MD
Organizational Affiliation
UT MD Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
UT MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
M.D. Anderson Cancer Center's website

Learn more about this trial

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

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