A Study of AS1411 Combined With Cytarabine in the Treatment of Patients With Primary Refractory or Relapsed Acute Myeloid Leukemia

Study Overview
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Brief Summary
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This is an open label randomized controlled phase II study of AS1411 combined with Cytarabine in the treatment of patients with primary refractory or relapsed acute myeloid leukemia.

Official Title
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An Open-label Randomized Controlled Phase II Study of AS1411 Combined With Cytarabine in the Treatment of Patients With Primary Refractory or Relapsed Acute Myeloid Leukemia

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: AS1411
* Drug: Cytarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of AML as defined by the World Health Organization (WHO) classification (Vardiman 2009) Primary refractory AML (defined as a failure to achieve a CR or CRi after therapy with curative intent) or AML in first relapse ECOG Performance status 0, 1 or 2 Age > 18 and < 70 years For patients presenting with primary refractory AML, > 20% blasts on baseline bone marrow assessment For patients presenting with relapsed AML, > 5% blasts on baseline bone marrow assessment Exclusion Criteria: An initial diagnosis of acute promyelocytic leukemia (as defined by French-American-British criteria (Bennett 1976)) Secondary AML, defined as AML evolving from antecedent hematological disorder or prior exposure to leukemogenic therapy or agent Clinically active CNS leukemia Previously received a total cumulative dose of cytarabine > 6g/m2 in the last 6 months Previously received > 1 induction regimen (Defined as 1 or 2 cycles of a drug or a drug combination administered as remission induction therapy)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br>cytarabine 2g/m2 bid Days 4-7 | Drug: Cytarabine<br>* Cytarabine 2g/m2 bid Days 4-7<br>* Other names: Ara-C;|
| Experimental: AS1411-40<br>AS1411 40mg/kg/day d1-7 plus cytarabine 2g/m2 bid days 4-7 | Drug: AS1411<br>* AS1411 40mg/kg/day or AS1411 80mg/kg/day<br>Drug: Cytarabine<br>* Cytarabine 2g/m2 bid Days 4-7<br>* Other names: Ara-C;|
| Experimental: AS1411-80<br>AS1411 80mg/kg/day d1-7, cytarabine 2g/m2 bid days 4- 7/ bid d4-7 | Drug: AS1411<br>* AS1411 40mg/kg/day or AS1411 80mg/kg/day<br>Drug: Cytarabine<br>* Cytarabine 2g/m2 bid Days 4-7<br>* Other names: Ara-C;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the response rate (CR + CRi) of AS1411 at 40 and 80mg/kg/day in combination with cytarabine therapy with the response rate (CR + CRi) of cytarabine therapy alone |  | Dec 2011 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare duration of remission, disease free survival and overall survival of AS1411 at 40 or 80mg/kg/day in combination with cytarabine therapy with that of cytarabine alone. |  | Dec 2011 | 
| To compare the time to hematological recovery of AS1411 at 40 or 80mg/kg/day in combination with cytarabine therapy with that of cytarabine alone. |  | Dec 2011 | 
| To compare the safety of AS1411 at 40 or 80mg/kg/day in combination with cytarabine therapy with that of cytarabine alone. |  | Dec 2011 | 
| To evaluate and compare a range of PD markers in patients administered AS1411 in combination with cytarabine therapy with the same PD markers in patients administered cytarabine therapy alone. |  | Dec 2011 | 
| To further define the PK of AS1411 |  | Dec 2011 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AS1411, AML, relapsed, refractory, aptamer, nucleolin