Azacitidine, Mitoxantrone Hydrochloride, and Etoposide in Treating Older Patients With Poor-Prognosis Acute Myeloid Leukemia
This phase I clinical trial studies the best dose of azacitidine and to see how well it works with mitoxantrone hydrochloride and etoposide in treating older patients with poor-prognosis acute myeloid leukemia. 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.
Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
Adult Acute Basophilic Leukemia
Adult Acute Eosinophilic Leukemia
Adult Acute Megakaryoblastic Leukemia (M7)
Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
Adult Acute Monoblastic Leukemia (M5a)
Adult Acute Monocytic Leukemia (M5b)
Adult Acute Myeloblastic Leukemia With Maturation (M2)
Adult Acute Myeloblastic Leukemia Without Maturation (M1)
Adult Acute Myeloid Leukemia in Remission
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Adult Acute Myelomonocytic Leukemia (M4)
Adult Erythroleukemia (M6a)
Adult Pure Erythroid Leukemia (M6b)
Recurrent Adult Acute Myeloid Leukemia
Secondary Acute Myeloid Leukemia
Untreated Adult Acute Myeloid Leukemia
Drug: mitoxantrone hydrochloride
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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)|
- Maximum-tolerated dose of azacitidine that can be safely combined with mitoxantrone hydrochloride and etoposide chemotherapy [ Time Frame: Up to 2 courses of treatment ] [ Designated as safety issue: Yes ]The descriptions and grading scales found in the revised National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
- Complete response rate [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
- Changes in topoisomerase II levels [ Time Frame: Baseline to day 4 ] [ Designated as safety issue: No ]These will be compared between responders (i.e. those achieving either CR or morphologic leukemia-free state [MLFS]) vs. non-responders (those not achieving CR/MLFS after 1-2 induction cycles), with 95% confidence intervals and 2-tailed t-tests of significance. Similar, nonquantitative comparisons will be made between responders and non-responders with respect to changes in DNA methylation and gene expression.
- Relapse-free survival [ Time Frame: From documentation of CR or MLFS to time of disease recurrence or last follow up, assessed up to 4 years ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: From the start of study treatment until death from any cause or last follow up, assessed up to 4 years ] [ Designated as safety issue: No ]
|Study Start Date:||December 2010|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Experimental: Treatment (azacitidine, mitoxantrone hydrochloride, etoposide)
Patients receive induction therapy comprising azacitidine SC 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.
Other Names:Drug: mitoxantrone hydrochloride
Other Names:Drug: etoposide
Other Names:Other: laboratory biomarker analysis
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.
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01260714
|Juravinski Cancer Centre at Hamilton Health Sciences|
|Hamilton, Ontario, Canada, L8V 5C2|
|University Health Network-Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|Principal Investigator:||Joseph Brandwein||University Health Network-Princess Margaret Hospital|