Decitabine Followed by Mitoxantrone Hydrochloride, Etoposide, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes
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|ClinicalTrials.gov Identifier: NCT01729845|
Recruitment Status : Completed
First Posted : November 20, 2012
Results First Posted : January 12, 2018
Last Update Posted : February 7, 2019
|Condition or disease||Intervention/treatment||Phase|
|Previously Treated Myelodysplastic Syndrome Recurrent Adult Acute Myeloid Leukemia||Drug: Cytarabine Drug: Decitabine Drug: Etoposide Other: Laboratory Biomarker Analysis Drug: Mitoxantrone Hydrochloride||Phase 1 Phase 2|
I. Estimate the maximum tolerated dose (MTD) of decitabine priming followed by sequential mitoxantrone hydrochloride/etoposide/cytarabine (MEC) chemotherapy in adults with relapsed/refractory acute myeloid leukemia (AML).
I. Determine, within the limits of a Phase 1/2 study, disease response and duration of remission.
II. Identify biomarkers (e.g., deoxyribonucleic acid [DNA] methylation and/or gene expression changes) associated with treatment responses.
OUTLINE: This is a phase I, dose-escalation study of decitabine followed by a phase II study.
Patients receive decitabine intravenously (IV) on days -9 to -5 (dose level 1), days -11 to -5 (dose level 2), or days -14 to -5 (dose level 3).
INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving complete response (CR) or CR with incomplete platelet count recovery (CRp) may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy.
After completion of study treatment, patients are followed up every 3 months for up to 5 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||52 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Mitoxantrone, Etoposide, and Cytarabine (MEC) Following Epigenetic Priming With Decitabine in Adults With Relapsed/Refractory Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndromes (MDS): A Phase 1/2 Study|
|Actual Study Start Date :||December 20, 2012|
|Actual Primary Completion Date :||August 25, 2016|
|Actual Study Completion Date :||April 3, 2017|
Experimental: Treatment (decitabine, MEC)
Patients receive decitabine IV on days -9 to -5 (dose level 1), days -11 to -5 (dose level 2), or days -14 to -5 (dose level 3).
INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy.
Other: Laboratory Biomarker Analysis
Drug: Mitoxantrone Hydrochloride
- Most Efficacious and Tolerated Dosage of Decitabine (Period 1) [ Time Frame: through day 45 ]MTD (most tolerated dose) of decitabine, measured in number of dose limiting toxicities. MTD defined as the highest dose in which the incidence of dose limiting toxicity is < 33%, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Phase I)
- Remission Rate Including CR and CRp [ Time Frame: Up to 5 years ]
Complete remission (CR) and Complete remission with incomplete platelet recovery (CRp) categorized according to criteria recommended by International Working Groups:
Complete resolution of disease-related symptoms and signs including palpable hepatosplenomegaly; hemoglobin level at least 110 g/L, platelet count at least 100x10^9/L, and absolute neutrophil count at least 1.0 x10^9/L. In addition, all 3 blood counts should be no higher than the upper normal limit; Normal leukocyte differential; Bone marrow histologic remission defined as the presence of age-adjusted normocellularity, no more than 5% myeloblasts, and an osteomyelofibrosis grade no higher than 1.
- Duration of Relapse-free Survival (for Patients Achieving CR or CRp) [ Time Frame: Up to 5 years ]Categorized according to criteria recommended by International Working Groups.
- Overall Survival [ Time Frame: Up to 5 years ]Survival measured as of day of last contact. Categorized according to criteria recommended by International Working Groups.
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): NCT01729845
|United States, Washington|
|Kadlec Clinic Hematology and Oncology|
|Kennewick, Washington, United States, 99336|
|EvergreenHealth Medical Center|
|Kirkland, Washington, United States, 98033|
|Fred Hutch/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Anna Halpern||Fred Hutch/University of Washington Cancer Consortium|