Azacitidine, Mitoxantrone Hydrochloride, and Etoposide in Treating Older Patients With Poor-Prognosis Acute Myeloid Leukemia

NCT01260714 | Terminated Phase 1 DMC

• 6 other identifiers: NCI-2011-02559CDR0000690647PHL-0748331N01CM00032N01CM62203
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trial studies the best dose of azacitidine and to see how well it works with mitoxantrone hydrochloride and etoposide in treating older patients with acute myeloid leukemia that has a lower chance of responding to treatment or higher risk of returning (poor prognosis). Drugs used in chemotherapy, such as azacitidine, mitoxantrone hydrochloride, and etoposide, 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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Maximum-tolerated dose of azacitidine that can be safely combined with mitoxantrone hydrochloride and etoposide chemotherapy

  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.

  Up to 2 courses of treatment

Secondary Outcomes (6)

• Changes in DNA methylation

  Baseline to day 4

• Changes in gene expression

  Baseline to day 4

• Changes in topoisomerase II levels

  Baseline to day 4

• Complete response rate

  Up to 4 years

• Overall survival

  From the start of study treatment until death from any cause or last follow up, assessed up to 4 years

Study Arms (1)

Treatment (azacitidine, mitoxantrone hydrochloride, etoposide)

EXPERIMENTAL

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.

Drug: Azacitidine; Drug: Etoposide; Other: Laboratory Biomarker Analysis; Drug: Mitoxantrone Hydrochloride

Interventions

Azacitidine DRUG

Given SC

Also known as: 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza

Treatment (azacitidine, mitoxantrone hydrochloride, etoposide)

Etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213

Treatment (azacitidine, mitoxantrone hydrochloride, etoposide)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (azacitidine, mitoxantrone hydrochloride, etoposide)

Mitoxantrone Hydrochloride DRUG

Given IV

Also known as: CL 232315, DHAD, DHAQ, Dihydroxyanthracenedione Dihydrochloride, Mitoxantrone Dihydrochloride, Mitoxantroni Hydrochloridum, Mitozantrone Hydrochloride, Mitroxone, Neotalem, Novantrone, Onkotrone, Pralifan

Treatment (azacitidine, mitoxantrone hydrochloride, etoposide)

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Acute myeloid leukemia (AML) as defined by World Health Organization (WHO) criteria, any subtype, de novo or secondary, except acute promyelocytic leukemia (APL)
• One of the following:
• Previously untreated, with adverse-risk cytogenetics, including any one of the following:
• Complete or partial deletion of chromosome 7
• Complete or partial deletion of chromosome 5
• At least 3 numerical or structural abnormalities, other than t(15;17), t(8;21) or inv(16) or variant
• q23 abnormalities
• Inv(3) or variant such as t(3:3)
• Previously untreated, transformed from prior myelodysplastic syndrome (MDS) or myeloproliferative disorder (MPD) other than CML
• Persistent leukemia following one cycle of 3+7 induction therapy (cytarabine plus either daunorubicin or idarubicin), any cytogenetic risk group
• Left ventricular ejection fraction (LVEF) \> 50% based on multi gated acquisition scan (MUGA) scan or 2-dimensional (2-D) echocardiogram
• Serum creatinine =\< 1.5 x upper limit of normal (ULN)
• Serum bilirubin =\< 1.5 x ULN
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky \>= 60%)

You may not qualify if:

• Patients who have had chemotherapy, radiotherapy or investigational agents within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients who have received prior radiation greater than 3000 cGy to marrow producing areas
• Patients may not be receiving any other investigational agents
• Patients with active central nervous system (CNS) leukemia; prior CNS leukemia is permitted provided the cerebrospinal fluid has cleared and there is no other evidence of active CNS leukemia
• Prior therapy for AML with decitabine, azacitidine, mitoxantrone, or etoposide
• Prior therapy with azacitidine or decitabine for pre-existing MDS
• History of allergic reactions attributed to decitabine, azacitidine, etoposide, mitoxantrone, or compounds of similar chemical or biologic composition
• Uncontrolled intercurrent illness including, but not limited to, active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Human immunodeficiency virus (HIV)-positive patients with cluster of differentiation (CD) counts less than 500/mm\^3 and/or a history of HIV/acquired immune deficiency syndrome (AIDS)-related complications will be excluded from the study

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Leukemia, Basophilic, Acute; Leukemia, Eosinophilic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Myeloid, Acute; Leukemia, Erythroblastic, Acute

Interventions

Azacitidine; Etoposide; Mitoxantrone

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Anthraquinones; Anthrones; Anthracenes; Quinones

Study Officials

• Joseph Brandwein

  University Health Network-Princess Margaret Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2010
• First Posted: December 15, 2010
• Study Start: December 1, 2010
• Primary Completion: March 1, 2015
• Study Completion: June 1, 2015
• Last Updated: August 20, 2015

Record last verified: 2015-06

Locations

CA (2)