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COMPLETEDPHASE1/PHASE2

Decitabine Followed by Mitoxantrone Hydrochloride, Etoposide, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes

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

NCT01729845•Fred Hutchinson Cancer Center

View on ClinicalTrials.gov

Summary

This phase I/II trial studies the side effects and best dose of decitabine followed by mitoxantrone hydrochloride, etoposide, and cytarabine and to see how well they work in treating patients with acute myeloid leukemia or high-risk myelodysplastic syndrome that has returned after a period of improvement or does not respond to treatment. Drugs used in chemotherapy, such as mitoxantrone hydrochloride, etoposide, cytarabine, and decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

Detailed Description

PRIMARY OBJECTIVES: 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). SECONDARY OBJECTIVES: 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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Prior diagnosis of "high-risk" myelodysplastic syndrome (MDS) (\>= 10% blasts) or AML other than acute promyelocytic leukemia (APL) with t(15;17) (q22;q12) or variants according to the 2008 World Health Organization (WHO) classification; patients with biphenotypic AML are eligible
•Relapsed/persistent disease according to standard criteria requiring salvage therapy; outside diagnostic material is acceptable as long as peripheral blood and/or bone marrow slides are reviewed at the study institution; flow cytometric analysis of peripheral blood and/or bone marrow should be performed according to institutional practice guidelines
•Treatment-related mortality (TRM) score =\< 9.2 as calculated with simplified model
•Should be off any active therapy for AML with the exception of hydroxyurea for at least 14 days prior to study registration unless patient has rapidly progressive disease, and all grade 2-4 non-hematologic toxicities should have resolved
•May have previously received monotherapy with demethylating agents for MDS or AML
•May have previously received chemotherapy with MEC for MDS or AML
•Patients with symptoms/signs of hyperleukocytosis or white blood cells (WBC) \> 100,000/uL can be treated with leukapheresis or may receive up to 2 doses of cytarabine (up to 500 mg/m\^2/dose) prior to enrollment
•Bilirubin =\< 2 x institutional upper limit of normal (IULN) unless elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis (assessed within 7 days prior to study day 1)
•Serum creatinine =\< 1.5 x IULN (assessed within 7 days prior to study day 1)
•Left ventricular ejection fraction \>= 40%, assessed within 3 months prior to study day 1, e.g. by multi gated acquisition (MUGA) scan or echocardiography, or other appropriate diagnostic modality and no clinical evidence of congestive heart failure; if the patient had anthracycline-based therapy since the most recent cardiac assessment, cardiac evaluation should be repeated if there is clinical or radiographical suspicion of cardiac dysfunction, or if the previous cardiac assessment was abnormal
+2 more criteria

Exclusion Criteria

•Refractory/relapsing myeloid blast crisis of chronic myeloid leukemia (CML), unless patient is not considered candidate for tyrosine kinase inhibitor treatment
•Concomitant illness associated with a likely survival of \< 1 year
•Active systemic fungal, bacterial, viral, or other infection, unless disease is under treatment with anti-microbials and/or controlled or stable (e.g. if specific, effective therapy is not available/feasible or desired \[e.g. chronic viral hepatitis, human immunodeficiency virus (HIV)\]); patient needs to be clinically stable as defined as being afebrile and hemodynamically stable for 24 hours; patients with fever thought to be likely secondary to leukemia are eligible
•Known hypersensitivity to any study drug
•Pregnancy or lactation
•Patients may not be receiving any other investigational agents

Locations (3)

Kadlec Clinic Hematology and Oncology

Kennewick, Washington, United States

EvergreenHealth Medical Center

Kirkland, Washington, United States

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Key Dates

Start Date

December 20, 2012

Primary Completion Date

August 25, 2016

Completion Date

April 3, 2017

Last Updated

February 7, 2019

Enrollment

ACTUAL participants

Conditions

Previously Treated Myelodysplastic SyndromeRecurrent Adult Acute Myeloid Leukemia

Interventions

Cytarabine

DRUG

Decitabine

DRUG

Etoposide

DRUG

Laboratory Biomarker Analysis

OTHER

Mitoxantrone Hydrochloride

DRUG

Genetically Modified T-cell Immunotherapy in Treating Patients With Relapsed/Refractory Acute Myeloid Leukemia and Persistent/Recurrent Blastic Plasmacytoid Dendritic Cell Neoplasm

NCT02159495

Adult Acute Myeloid Leukemia in RemissionAcute Biphenotypic Leukemia+11 more

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COMPLETEDPHASE1

Donor Peripheral Stem Cell Transplant in Treating Patients With Hematolymphoid Malignancies

NCT01523223

Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)+32 more

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: February 7, 2019Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Decitabine Followed by Mitoxantrone Hydrochloride, Etoposide, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes

Inclusion Criteria

Exclusion Criteria

Genetically Modified T-cell Immunotherapy in Treating Patients With Relapsed/Refractory Acute Myeloid Leukemia and Persistent/Recurrent Blastic Plasmacytoid Dendritic Cell Neoplasm

Donor Peripheral Stem Cell Transplant in Treating Patients With Hematolymphoid Malignancies

Organ-Sparing Marrow-Targeted Irradiation Before Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies

Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Total Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome

Donor Bone Marrow Transplant With or Without G-CSF in Treating Young Patients With Hematologic Cancer or Other Diseases

High-Dose Chemotherapy With or Without Total-Body Irradiation Followed by Autologous Stem Cell Transplant in Treating Patients With Hematologic Cancer or Solid Tumors