The primary objectives of this study are:

1. To evaluate whether the addition of amifostine will allow for the safe administration of idarubicin at a dose of 21 mg/m² in combination with standard-dose ara-C in older patients with newly diagnosed, previously untreated acute myeloid leukemia (AML); and

2. To estimate the complete remission rate of induction therapy with amifostine, idarubicin (21 mg/m²), plus ara-C or induction therapy with idarubicin (12 mg/m²) plus ara-C in this patient population.

Condition	Treatment or Intervention	Phase
Leukemia Acute Myeloid Leukemia	Drug: Ethyol	Phase I Phase II

Ages Eligible for Study:  60 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Adult men and women of at least 60 years of age at the time of entry or randomization;
• Histologically proven AML with at least 20% myeloblasts based on bone marrow aspiration and biopsy performed within 5 days prior to entry or randomization;
• Candidates for aggressive induction chemotherapy in the judgment of the Investigator;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (see Appendix A) documented within 5 days prior to entry or randomization. For patients who are admitted to the hospital for evaluation and treatment of AML, ECOG performance status should be determined prior to admission. For patients who are admitted to the hospital for other reasons (e.g., acute medical problems), ECOG performance status should be determined prior to entry or randomization.
• Must be able to, in the opinion of the Investigator, safely stop taking antihypertensive medication 24 hours prior to amifostine administration;
• Women must be >1 year post-menopausal at the time the informed consent is signed. Men of reproductive potential must agree to practice an effective method of avoiding impregnation (including condom, abstinence, or sterile sexual partner) starting at the initiation of induction therapy (i.e., start of ara-C administration), and must agree to continue using such precautions while receiving idarubicin (± amifostine) and ara-C and for 30 days after the last dose of ara-C therapy;
• Aspartate transaminase (AST)/alanine transaminase (ALT) less than or equal to 2.5 times upper limit of normal (ULN) within 5 days prior to entry or randomization;
• Serum creatinine less than or equal to 2.0 mg/dL within 5 days prior to entry or randomization;
• Left ventricular ejection fraction (LVEF) greater than or equal to 50% on multiple gated acquisition (MUGA) scan or two-dimensional echocardiography (2-D ECHO) within 5 days prior to entry or randomization;
• Written informed consent (all sites) and HIPAA authorization (USA sites only) obtained from the patient prior to receipt of any study medication or beginning study procedures.

Exclusion Criteria:

• Prior cytotoxic therapy for AML (hydroxyurea or similar low-dose therapy to control the white count prior to initiation of induction therapy [i.e., start of ara-C administration] is not an exclusion);
• Diagnosis of acute promyelocytic leukemia (FAB M3 AML);
• Prior diagnosis of Myelodysplastic Syndrome (MDS) or AHD (Antecedent Hematologic Disorder, e.g. Polycythemia Vera);
• Known central nervous system (CNS) involvement;
• Life expectancy, in the opinion of the Investigator, of < 3 months due to co-morbid conditions unrelated to AML;
• History of prior malignancies that have required the administration of systemic cytotoxic chemotherapy or other systemic bone marrow cytotoxic agents or therapies, or radiation therapy of any kind to areas of the body containing bone marrow;
• Prior treatment with other investigational agents within 4 weeks prior to entry or randomization;
• Current or planned participation (from the day of entry or randomization through 30 days after the last dose of ara-C therapy) in a research protocol in which an investigational agent or therapy may be administered;
• Infection with human immunodeficiency virus (HIV) or active viral hepatic infections based on patient’s medical history elicited by the Investigator within 5 days prior to entry or randomization;
• Any evidence of or history elicited by the Investigator of angina, acute or chronic congestive heart failure, or pericardial effusion within 6 months prior to entry or randomization;
• Any evidence of or history elicited by the Investigator of uncontrolled or refractory hypertension despite medication within 6 months prior to entry or randomization;
• Any evidence of or history elicited by the Investigator of a myocardial infarction within the last 6 months and LVEF <50% within 5 days prior to entry or randomization on MUGA scan or 2-D ECHO;
• Any evidence of cerebrovascular accident (CVA) with unstable neural deficits within 6 months prior to entry or randomization;
• Any evidence of transient ischemia attack (TIA) or symptomatic cerebrovascular disease within 6 months prior to entry or randomization;
• Any evidence of clinically significant cardiac arrhythmia that cannot be controlled with medication or is unstable or symptomatic within 2 months prior to entry or randomization;
• A general medical or psychological condition or behavior, including substance dependence or abuse that, in the opinion of the Investigator, might not permit the patient to complete the study or sign the informed consent.

Illinois
      Springfield Clinic, Springfield,  Illinois,  62703,  United States
Indiana
      Indiana Oncology Hematology Consultants, Indianapolis,  Indiana,  46202,  United States
      Cancer Care Center, New Albany,  Indiana,  47150,  United States
Kansas
      University of Kansas Medical Center, Kansas City,  Kansas,  66160,  United States
Michigan
      Cancer Management Specialists, Grosse Pointe Woods,  Michigan,  48236,  United States
New Jersey
      St. Barnabas Health Care Center, Newark,  New Jersey,  07112,  United States
New York
      Roswell Park Cancer Institute, Buffalo,  New York,  14263,  United States
North Carolina
      Wake Forest University School of Medicine, Winston Salem,  North Carolina,  27157-1082,  United States
Ohio
      Cleveland Clinic, Cleveland,  Ohio,  44195,  United States
Pennsylvania
      Thomas Jefferson University Medical College, Philadelphia,  Pennsylvania,  19107,  United States
Tennessee
      Baptist Clinical Research Center, Memphis,  Tennessee,  38120,  United States
Wisconsin
      Medical College of Wisconsin, Milwaukee,  Wisconsin,  53226,  United States

Study ID Numbers:  MI-CP103
Record last reviewed:  December 2004
Last Updated:  December 29, 2004
Record first received:  June 23, 2004
ClinicalTrials.gov Identifier:  NCT00086099
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08