Study of CEP-701 (Lestaurtinib) in Patients With Acute Myeloid Leukemia (AML)

Study Overview
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Brief Summary
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The purpose of the study is to determine whether CEP-701 given in sequence with induction chemotherapy increases the proportion of patients with relapsed acute myeloid leukemia (AML) who achieve a second complete remission (CR).

Detailed Description
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Patients randomly assigned to chemotherapy alone received the second course of induction chemotherapy as soon as clinically indicated; patients randomly assigned to receive chemotherapy plus sequential lestaurtinib had lestaurtinib withheld for 3 days (72 hours) before the start of the second 5-day course of chemotherapy and resumed lestaurtinib treatment 2 days (48 hours) after the final administration of the second course of chemotherapy.

Official Title
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A Randomized, Open-Label Study of Oral CEP-701 Administered in Sequence With Standard Chemotherapy to Patients With Relapsed Acute Myeloid Leukemia (AML) Expressing FLT-3 Activating Mutations

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: CEP-701
* Drug: high-dose cytarabine
* Drug: Mitozantrone, Etoposide, Cytarabine (combination Chemotherapy)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: cytological confirmation of AML; relapsed disease following first CR of 1 month(30days)to 24 months(730days). The time from first relapse to study entry (start of first course of induction chemotherapy) must be no longer than 30days; confirmation of FLT-3 activating mutation positive status after point of initial relapse; aged 18 years or older; written informed consent; ability to understand and comply with study restrictions; no comorbid conditions that would limit life expectancy to less than 3 months; ECOG Performance Score of 0, 1,or 2; women must be neither pregnant nor lactating, and either of non-childbearing potential or using adequate contraception with a negative pregnancy test at study entry Exclusion criteria: bilirubin > 2x ULN; ALT/AST > 3x ULN; serum creatinine > 1.5 mg/dL; resting ejection fraction of left ventricle l < 45%(applies only to patients scheduled to receive mitoxantrone, etoposide, and cytarabine [MEC]; untreated or progressive infection; any physical or psychiatric cdtn that may compromise participation in the study; known CNS involvement with AML; any previous treatment with a FLT-3 inhibitor; requires current treatment for HIV with protease inhibitors; active GI ulceration or bleeding; use of an investigational drug that is not expected to be cleared by the start of CEP-701 treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Induction chemotherapy with or without sequential treatment with oral CEP-701 at 80 mg bid. For patients with duration of first CR of 1 to 6 months, the induction regimen will be MEC. | Drug: CEP-701<br> <br> * Other names: lestaurtinib;Drug: Mitozantrone, Etoposide, Cytarabine (combination Chemotherapy)<br>* Chemotherapy<br>* Other names: MEC;|
| Active Comparator: 2<br>Induction chemotherapy with or without sequential treatment with oral CEP-701 at 80 mg bid. For patients with duration of first CR of more than 6 months to 24 months, the induction regimen will be HiDAC. | Drug: CEP-701<br> <br> * Other names: lestaurtinib;Drug: high-dose cytarabine<br>* Chemotherapy<br>* Other names: HiDAC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine whether CEP-701 given in sequence with induction chemotherapy increases the proportion of patients with relapsed AML who achieve a second complete remission or a complete remission with incomplete platelet count recovery. |  | 113 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| - overall survival - event-free survival - remission duration - safety and tolerability of CEP-701 - pharmacokinetics of CEP-701 - CEP-701 inhibitory activity |  | 113 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML