Azacytidine Plus FLAG for Relapsed or Refractory AML

Phase 2

• Conditions: Acute Myeloid Leukemia
• Interventions: Drug: Azacytidine; Drug: Fludarabine; Drug: Cytarabine; Drug: Filgrastim

• Registration Number: NCT02275663
• Lead Sponsor: King Fahad Medical City

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-10-20
• Study First Submitted QC: 2014-10-23
• Study First Posted: 2014-10-27
• Study Start: 2014-12
• Status Verified: 2015-01
• Last Update Submitted: 2015-01-04
• Last Update Posted: 2015-01-06
• Primary Completion: 2017-10
• Study Completion: 2018-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 37

Inclusion Criteria

1. Age 16 to 60

2. Patients with a diagnosis of relapse or refractory AML (≥ 20% blast in bone marrow).

3. Eastern Cooperative Oncology Group (ECOG) performance status ≤2

4. 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

1. Patients with a diagnosis of acute promyelocytic leukemia (AML -M3)
2. Pregnant women
3. Patients previously treated with fludarabine are allowed to participate.
4. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Azacytidine plus FLAG	Azacytidine	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.
Azacytidine plus FLAG	Fludarabine	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.
Azacytidine plus FLAG	Cytarabine	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.
Azacytidine plus FLAG	Filgrastim	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.

Primary Outcome Measures

Name	Time	Method
complete response rate	6 weeks	bone marrow blast \<5% with complete neutrophil (\>1000/ul) and platelets (\>100,000/ul) recovery

Secondary Outcome Measures

Name	Time	Method
leukemia free survival	1-3 years	from time of complete remission to time of relapse or death
overall survival	1-3 yeears	from date of enrolment to date of death
one year leukemia free survival	1 year	probability of leukemia free survival at one year of enrolment

Trial Locations

Locations (1)

King Fahad Medical City; 🇸🇦 Riyadh, Saudi Arabia