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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2015 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01729845
First received: November 15, 2012
Last updated: July 8, 2015
Last verified: July 2015
  Purpose

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 that has returned after a period of improvement or does not respond to treatment or high-risk myelodysplastic syndromes. 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 or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.


Condition Intervention Phase
Acute Biphenotypic Leukemia
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

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • MTD of decitabine 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) [ Time Frame: Day 45 ] [ Designated as safety issue: Yes ]
  • Remission rate including CR and CRp (Phase II) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Categorized according to criteria recommended by International Working Groups.


Secondary Outcome Measures:
  • Disease-free survival (for patients achieving CR or CRp) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Categorized according to criteria recommended by International Working Groups.

  • Event-free survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Categorized according to criteria recommended by International Working Groups.

  • Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Categorized according to criteria recommended by International Working Groups.


Estimated Enrollment: 52
Study Start Date: December 2012
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Drug: Cytarabine
Given IV
Other Names:
  • .beta.-Cytosine arabinoside
  • 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-.beta.-D-Arabinofuranosylcytosine
  • 1.beta.-D-Arabinofuranosylcytosine
  • 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
  • Alexan
  • Ara-C
  • ARA-cell
  • Arabine
  • Arabinofuranosylcytosine
  • Arabinosylcytosine
  • Aracytidine
  • Aracytin
  • Aracytine
  • Beta-Cytosine Arabinoside
  • CHX-3311
  • CYTARABINE
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosar-U
  • Cytosine Arabinoside
  • Cytosine-.beta.-arabinoside
  • Erpalfa
  • Starasid
  • Tarabine PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453
Drug: Decitabine
Given IV
Other Names:
  • 5-Aza-2'-deoxycytidine
  • Dacogen
  • DECITABINE
  • Decitabine for Injection
  • Deoxyazacytidine
  • Dezocitidine
Drug: Etoposide
Given IV
Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • ETOPOSIDE
  • Lastet
  • Toposar
  • Vepesid
  • VP 16-213
  • VP-16
  • VP-16-213
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Mitoxantrone Hydrochloride
Given IV
Other Names:
  • CL 232315
  • DHAD
  • DHAQ
  • Dihydroxyanthracenedione Dihydrochloride
  • Mitoxantrone Dihydrochloride
  • MITOXANTRONE HYDROCHLORIDE
  • Mitoxantroni Hydrochloridum
  • Mitozantrone Hydrochloride
  • Mitroxone
  • Neotalem
  • Novantrone
  • Onkotrone
  • Pralifan

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  • Patients with prior autologous or allogeneic hematopoietic cell transplantation (HCT) are eligible if relapse occurs provided symptoms of graft-versus host disease are well controlled with stable use of immunosuppressive agents
  • 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 registration)
  • Serum creatinine =< 1.5 x IULN (assessed within 7 days prior to registration)
  • Left ventricular ejection fraction >= 40%, assessed within 3 months prior to registration, 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
  • Women of childbearing potential and men must agree to use adequate contraception
  • Provide written informed consent

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 24-48 hours
  • Known hypersensitivity to any study drug
  • Pregnancy or lactation
  • Patients may not be receiving any other investigational agents
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01729845

Locations
United States, Washington
Kadlec Clinic Hematology and Oncology Completed
Kennewick, Washington, United States, 99336
EvergreenHealth Medical Center Completed
Kirkland, Washington, United States, 98033
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Anna Halpern    206-667-6233    halpern2@uw.edu   
Principal Investigator: Anna Halpern         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Anna Halpern Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01729845     History of Changes
Other Study ID Numbers: 2652.00, NCI-2012-02224, 2652, 2652.00, P30CA015704
Study First Received: November 15, 2012
Last Updated: July 8, 2015
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Leukemia, Myeloid, Acute
Leukemia
Leukemia, Biphenotypic, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Immune System Diseases
Immunoproliferative Disorders
Leukemia, Lymphoid
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Azacitidine
Cytarabine
Decitabine
Etoposide
Etoposide phosphate
Mitoxantrone
Analgesics
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 26, 2015