NCT01260714

Azacitidine, Mitoxantrone Hydrochloride, and Etoposide in Treating Older Patients With Poor-Prognosis Acute Myeloid Leukemia

A Phase I Study of Azacitidine Combined With Mitoxantrone and Etoposide (A-NOVE) Chemotherapy for Patients' Age ≥ 60 With Poor Prognosis Acute Myeloid Leukemia (AML)

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 13 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 60 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the best dose of azacitidine and to see how well it works with mitoxantrone hydrochloride and etoposide in treating older patients with acute myeloid leukemia that has a lower chance of responding to treatment or higher risk of returning (poor prognosis). Drugs used in chemotherapy, such as azacitidine, mitoxantrone hydrochloride, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

Detailed description

PRIMARY OBJECTIVES: I. To determine the highest tolerated dose of two dosing schedules of azacitidine when combined with mitoxantrone (mitoxantrone hydrochloride) and etoposide (A-NOVE) chemotherapy in poor prognosis older patients with acute myeloid leukemia (AML). II. To evaluate the toxicity of this regimen. SECONDARY OBJECTIVES: I. To determine the complete response (CR) rate and using this regimen. II. To evaluate changes in topoisomerase II activity, deoxyribonucleic acid (DNA) methylation and DNA expression arrays in leukemia cells during azacitidine treatment, and to correlate these changes with responses to A-NOVE chemotherapy. III. To evaluate relapse-free survival (RFS) and overall survival (OS) in patients receiving post-remission consolidation with A-NOVE in patients achieving CR. (OS follow-up discontinued as of 08/07/2014) OUTLINE: This is a dose-escalation study of azacitidine. Patients receive induction therapy comprising azacitidine subcutaneously (SC) once daily (QD) on days 1-7, mitoxantrone hydrochloride IV over 30 minutes, and etoposide IV over 1 hour on days 4-8. Patients may receive up to 2 additional courses of the same treatment as re-induction or consolidation therapy beginning 35-60 days from the start of the previous course. After completion of study treatment, patients are followed up every 3 months.

Conditions

• Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
• Adult Acute Basophilic Leukemia
• Adult Acute Eosinophilic Leukemia
• Adult Acute Megakaryoblastic Leukemia
• Adult Acute Monoblastic Leukemia
• Adult Acute Monocytic Leukemia
• Adult Acute Myeloid Leukemia in Remission
• Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11
• Adult Acute Myeloid Leukemia With Maturation
• Adult Acute Myeloid Leukemia With Minimal Differentiation
• Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11
• Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1
• Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL
• Adult Acute Myeloid Leukemia Without Maturation
• Adult Acute Myelomonocytic Leukemia
• Adult Erythroleukemia
• Adult Pure Erythroid Leukemia
• Alkylating Agent-Related Acute Myeloid Leukemia
• Recurrent Adult Acute Myeloid Leukemia
• Secondary Acute Myeloid Leukemia
• Untreated Adult Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Azacitidine	Given SC
DRUG	Etoposide	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Mitoxantrone Hydrochloride	Given IV

Timeline

• Start date: 2010-12-01
• Primary completion: 2015-03-01
• Completion: 2015-06-01
• First posted: 2010-12-15
• Last updated: 2015-08-20

Locations

2 sites across 1 country: Canada