Azacitidine, Mitoxantrone Hydrochloride, and Etoposide in Treating Older Patients With Poor-Prognosis Acute Myeloid Leukemia
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|ClinicalTrials.gov Identifier: NCT01260714|
Recruitment Status : Terminated (Inadequate accrual rate)
First Posted : December 15, 2010
Last Update Posted : August 20, 2015
|Condition or disease||Intervention/treatment||Phase|
|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||Drug: Azacitidine Drug: Etoposide Other: Laboratory Biomarker Analysis Drug: Mitoxantrone Hydrochloride||Phase 1|
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. (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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||13 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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)|
|Study Start Date :||December 2010|
|Actual Primary Completion Date :||March 2015|
|Actual Study Completion Date :||June 2015|
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: Laboratory Biomarker Analysis
Drug: Mitoxantrone Hydrochloride
- Maximum-tolerated dose of azacitidine that can be safely combined with mitoxantrone hydrochloride and etoposide chemotherapy [ Time Frame: Up to 2 courses of treatment ]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.
- Changes in DNA methylation [ Time Frame: Baseline to day 4 ]Nonquantitative comparisons will be made between responders and non-responders with respect to changes in DNA methylation.
- Changes in gene expression [ Time Frame: Baseline to day 4 ]Nonquantitative comparisons will be made between responders and non-responders with respect to changes in gene expression.
- Changes in topoisomerase II levels [ Time Frame: Baseline to day 4 ]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.
- Complete response rate [ Time Frame: Up to 4 years ]
- Overall survival [ Time Frame: From the start of study treatment until death from any cause or last follow up, assessed up to 4 years ]
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|