NCT03263936

Epigenetic Reprogramming in Relapse/Refractory AML

Epigenetic Reprogramming in Relapse AML: A Phase 1 Study of Decitabine and Vorinostat Followed by Fludarabine, Cytarabine and G-CSF (FLAG) in Children and Young Adults With Relapsed/Refractory AML

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 37 (actual)
• Sponsor: Therapeutic Advances in Childhood Leukemia Consortium · Academic / Other
• Sex: All
• Age: 1 Year – 25 Years
• Healthy volunteers: Not accepted

Summary

This is a pilot study using decitabine and vorinostat before and during chemotherapy with fludarabine, cytarabine and G-CSF (FLAG).

Detailed description

Decitabine is a demethylating agent and vorinostat is a HDAC inhibitor. The use of demethylating agents and HDAC inhibitors in combination have been previously shown to have synergistic effects in altering neoplastic pathways of cancer cells and be well tolerated in human clinical studies. With the ability of decitabine and vorinostat to alter the abnormal cellular pathways of leukemic blasts and essentially turn off anti-apoptotic proteins, the leukemia cells have become primed for cytotoxic cell kill via chemotherapeutic agents. This study will ask the question as to whether or not the combination of decitabine and vorinostat followed by chemotherapy is feasible and whether it can positively impact outcome in patients with relapsed or refractory acute myelogenous leukemia.

Conditions

• Acute Myelogenous Leukemia

Interventions

Type	Name	Description
DRUG	Decitabine	Dose Level #0: 5 mg/m2 Dose Level #1: 7.5 mg/m2 Dose Level #2: 10 mg/m2 Dose Level #3: 15 mg/m2 Dose Level #4: 20 mg/m2 given IV over \_\_ hour on days 1 through 5
DRUG	Vorinostat	Age \<18: 180 mg/m2/day once daily PO. Age≥18: 200 mg twice daily PO.
DRUG	Filgrastim (G-CSF)	Given on days 5 until evidence of ANC recovery (\>500/µL)5µg/kg/dose IV or SQ (starting at hour 0)
DRUG	Fludarabine	30 mg/m2/day IV over 30 minutes (starting at Hour 0 - Immediately after G-CSF)
DRUG	Cytarabine	2000 mg/m2/day (Starting at Hour 0.5),IV over 3 hours, days 6-10

Timeline

• Start date: 2017-07-11
• Primary completion: 2020-07-09
• Completion: 2022-02-10
• First posted: 2017-08-28
• Last updated: 2025-10-16
• Results posted: 2025-10-16

Locations

33 sites across 3 countries: United States, Australia, Canada

Regulatory

• FDA-regulated drug study