Decitabine Followed by Mitoxantrone Hydrochloride, Etoposide, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes
|ClinicalTrials.gov Identifier: NCT01729845|
Recruitment Status : Completed
First Posted : November 20, 2012
Results First Posted : January 12, 2018
Last Update Posted : January 17, 2018
|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.
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|