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

• Status: Terminated
• Trial end date: 2015-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Azacitidine; Etoposide; Etoposide phosphate; Mitoxantrone; Podophyllotoxin

Criteria

Inclusion Criteria:

• 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

• 11q23 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%)

• Patients with high initial white blood cell (WBC) should have the WBC reduced to below 50 x 10^9/L with hydroxyurea, to minimize the risk of leukostasis related-complications; hydroxyurea is permitted up to 24 hours prior to starting azacitidine

• Men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; men should not father a child while participating in this study

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• 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