Azacytidine Plus FLAG for Relapsed or Refractory AML

Study Overview
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Brief Summary
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The purpose of this phase 2 study is to test the efficacy of azacytidine given prior to fludarabine, cytarabine, and G-CSF for the treatment of relapsed or refractory acute myeloid leukemia.

Official Title
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Phase 2 Study of 5 Days Azacytidine Priming Prior to Fludarabine, Cytarabine and Granulocyte-Colony Stimulating Factor (G-CSF) Combination for Patients With Relapsed or Refractory AML

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Azacytidine
* Drug: Fludarabine
* Drug: Cytarabine
* Drug: Filgrastim


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 16 to 60 Patients with a diagnosis of relapse or refractory AML (≥ 20% blast in bone marrow). Eastern Cooperative Oncology Group (ECOG) performance status ≤2 Patients must have preserved organ function as defined below: Creatinine ≤ 1.5 mg/dl Total bilirubin ≤ 1.5x upper limit of the normal Alanine aminotransferase (ALT) ≤ 2x upper limit of the normal Left ventricular ejection fraction (LVEF) ≥ 45% Exclusion Criteria: Patients with a diagnosis of acute promyelocytic leukemia (AML -M3) Pregnant women Patients previously treated with fludarabine are allowed to participate. Patients with Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 60 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Azacytidine plus FLAG<br>Azacytidine 75 mg/m2 = mg IV in 100 ml Normal Saline (NS) over 30 minutes on days -5 t0 -1 G-CSF 5 mcg/kg subcut on days 0 to + 6 Fludarabine 30mg/m² in 100ml NS IV daily over 30min., on Days +1 to +5 Cytarabine 2gm/m² = 500ml NS IV daily over 4h, on Days +1 to +5 Start 4h after completion of fludarabine infusion. | Drug: Azacytidine<br> <br> * Other names: vidaza;Drug: Fludarabine<br> <br> Drug: Cytarabine<br> <br> Drug: Filgrastim<br>* G-CSF<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| complete response rate | bone marrow blast <5% with complete neutrophil (>1000/ul) and platelets (>100,000/ul) recovery | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| leukemia free survival | from time of complete remission to time of relapse or death | 1-3 years | 
| overall survival | from date of enrolment to date of death | 1-3 yeears | 
| one year leukemia free survival | probability of leukemia free survival at one year of enrolment | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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relapsed AML, refractory AML, azacytidine