A Phase 1 Study of MLN518 Given in Combination With Standard Induction Chemotherapy for the Treatment of Patients With Newly Diagnosed Acute Myelogenous Leukemia
- Male or female patients, at least 18 years of age, with newly diagnosed (previously
untreated) AML, regardless of the mutational status of FLT3 in their leukemic blasts.
- Unequivocal histologic diagnosis of AML (based on the World Health Organization [WHO]
and/or FAB classifications), excluding acute promyelocytic leukemia. AML patients
with a history of antecedent myelodysplasia (MDS) are eligible for treatment in this
trial but must not have had prior cytotoxic therapy for MDS.
- No prior anti-neoplastic therapy for leukemia or MDS with the following exceptions:
- emergency leukapheresis;
- emergency treatment for hyperleukocytosis with hydroxyurea;
- growth factor/cytokine support.
- Eastern Cooperative Oncology Group performance status of 0 to 3
- Pretreatment laboratory test values within the following limits no more than 7 days
- total bilirubin equal or less then 1.5 x the upper limit of normal;
- Alanine aminotransferase and aspartate aminotransferase equal or less then 2.5 x
- serum creatinine equal or less then 2.0 mg/dL.
- Male patients must use an appropriate method of barrier contraception during the
- Female patients must be postmenopausal, surgically sterilized, or willing to use
reliable methods of birth control (ie, a hormonal contraceptive, an intrauterine
device, diaphragm with spermicide, or abstinence) for the duration of the study.
- Ability to voluntarily provide written informed consent before the performance of any
study related procedure not part of normal medical care.
- An active malignancy other than AML (with the exception of basal and/or squamous cell
skin cancers and curatively treated carcinoma of the cervix) at the time of study
- Suspected or confirmed diagnosis of acute promyelocytic leukemia [t
- Documented or suspected central nervous system (CNS) involvement with leukemia.
- Ongoing vomiting.
- Nausea of intensity greater than Grade 1 based on the National Cancer Institute
Common Terminology Criteria for Adverse Events (NCI CTCAE) categorization.
- Known gastrointestinal disease that could interfere with the oral absorption of
- Severe CNS, pulmonary, renal, or hepatic disease not related to the patient's AML.
- A left ventricular ejection fraction < 40%.
- Myocardial infarction within 6 months of enrollment or New York Heart Association
(NYHA) Class III or IV heart failure (see Appendix 3), uncontrolled angina, severe
uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
ischemia or active conduction system abnormalities.
- QTc > 500 msec.
- Known or suspected infection with human immunodeficiency virus (HIV).
- Known active infection with hepatitis B or hepatitis C.
- Known or suspected primary muscular or neuromuscular disease (eg, muscular dystrophy,
- Any serious medical or psychiatric illness that could, in the investigator's opinion,
potentially interfere with the completion of treatment according to this protocol.
- Inability to provide written informed consent to participate in this study.