Open Study of CEP-701 in Patients With Refractory Acute Myeloid Leukemia With FLT-3 Mutation

An Open-Label Study of CEP-701 in Patients With Refractory, Relapsed, or Poor Risk Acute Myeloid Leukemia Expressing FLT-3 Activating Mutations

The purpose of this study is to determine the response rate of patients with refractory, relapsed or poor risk AML expressing FLT-3 activating mutations, when administered CEP-701 at a dosage of 60 mg 2 times a day.

Study Overview

• Status: Completed
• Conditions: Leukemia, Myeloid
• Intervention / Treatment: Drug: CEP-701 60mg; Drug: Cep-701 80mg; Drug: Cep-701 40mg

Detailed Description

This is an open-label study of CEP-701 in patients with refractory, relapsed, or poor risk AML expressing FLT-3 activating mutations. Patients who meet eligibility criteria will be enrolled at a dosage of 60 mg orally 2 times a day for 28 days (1 cycle). Upon completion of cycle 1, the dosage may be increased to 80mg 2 times a day or decreased to 40 mg 2 times a day, dependent upon response to 60 mg dosage.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

INCLUSION CRITERIA:

• patient must have confirmed diagnosis of refractory or relapsed AML that expresses a FLT-3 mutation
• patient must have life expectancy of more than 2 months
• patient must be fully recovered from reversible side effects of previous therapy for cancer

EXCLUSION CRITERIA:

• total bilirubin, ALT or AST greater than 2 times upper limit of normal
• patient <65 years of age with estimated creatinine clearance less than 60 mL/min; patient >65 years of age with serum creatinine > 1.5 times the upper limit of normal (ULN)
• received any investigational drug within past 4 weeks
• GI disturbance/malabsorption that may affect absorption of CEP-701
• HIV positive
• received NSAID within prior 14 days
• has active infection

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cycle 1; 60mg	Drug: CEP-701 60mg; 60mg orally 2 times a day for 28 days
Experimental: Cycle 2; 80mg dependent upon response to Cycle 1	Drug: Cep-701 80mg; 80mg 2 times a day, dependent upon response to cycle 1
Experimental: Cycle 2b; 40mg dependent upon response to Cycle 1	Drug: Cep-701 40mg; 40mg 2 times a day, dependent upon response to cycle 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Samples and/or bone marrow assessments for complete remission (CR), complete tumor clearance (CTC), or hematologic response (HR) from bone marrow	Response rate of patients with refactory, relapsed, or poor risk acute myeloid leukemia (AML) expressing Fms-like tyrosine kinase 3 (FLT-3) activating mutations. CR is defined as presence of less than 5% myeloblasts in bone marrow with normalized peripheral blood cell counts. HR is defined as a 50% or more decrease in the absolute number of peripheral blast count or at least a 50% reduction in bone marrow blasts.	56 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of days to response	Response as defined by CR, CTC, or HR.	56 Days
Number of days to disease progression	Response as defined by CR, CTC, or HR.	56 Days
Levels of FLT-3 phosphorylation inhibition in vivo	The degree of inhibition of FLT-3 autophosphorylation measured in ex vivo bioassay plasma samples	56 Days

Collaborators and Investigators

• Sponsor: Cephalon

Study record dates

Study Major Dates

• Study Start: January 1, 2002
• Primary Completion (Actual): February 1, 2003
• Study Completion (Actual): February 1, 2003

Study Registration Dates

• First Submitted: February 7, 2002
• First Submitted That Met QC Criteria: February 7, 2002
• First Posted (Estimate): February 8, 2002

Study Record Updates

• Last Update Posted (Estimate): August 23, 2012
• Last Update Submitted That Met QC Criteria: August 14, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: AML; FLT-3 mutation
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: C0701a/202/ON/US