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

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Leukemia, Myeloid

Intervention / Treatment
-----------------
* Drug: CEP-701 60mg
* Drug: Cep-701 80mg
* Drug: Cep-701 40mg


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

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

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
AML, FLT-3 mutation