Study Evaluating the Addition of Amifostine (Ethyol®) to Idarubicin and Cytosine Arabinoside in Older Patients With Acute Myeloid Leukemia

Condition(s) targeted: Leukemia; Acute Myeloid Leukemia

Intervention: Ethyol (Drug)

Phase: Phase 1/Phase 2

Status: Active, not recruiting

Sponsored by: MedImmune LLC

Official(s) and/or principal investigator(s):
Ron Lieberman, MD, Study Director, Affiliation: MedImmune LLC

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.

Official title: A Phase IB/II, Randomized, Open-Label, Multicenter Study Evaluating Whether the Addition of Amifostine (Ethyol®) Will Enable the Safe Increase in Dose Intensity of Idarubicin in Combination With Cytosine Arabinoside in Older Patients With Newly Diagnosed, Previously Untreated Acute Myeloid Leukemia

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome:

Clinically significant hematologic and non-hematologic toxicities associated with idarubicin administration

Incidence rate of amifostine-associated hypotension results in amifostine dose reduction, discontinuation of amifostine, or causes the development of serious cardiovascular or cerebrovascular events will be estimated

Secondary outcome:

Duration of Complete Remission

Overall Survival

Minimum age: 60 Years. Maximum age: N/A. Gender(s): 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; History of prior MDS allowed provided the patient has received no prior cytotoxic therapy for MDS;

- 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

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 or MDS (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 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 within the last six (6 mos.) 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;

- History of prior anthracycline use;

- 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 prior to randomization;

- 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 including prolongation of QT

interval 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.

Kaplan Med. Center, Rehovot 76100, Israel

Rabin Medical Center, Petach Tikva 49100, Israel

Sheba Medical Center, Tel Hasomer 52620, Israel

Rambam Medical Center, Haifa 31096, Israel

Scripps Cancer Center, San Diego, California 92121, United States

Rush University Medical Center, Chicago, Illinois 60612, United States

Cancer Care Center, New Albany, Indiana 47150, United States

University of Kansas Medical Center, Kansas City, Kansas 66160, United States

Cancer Management Specialists (No longer Recruiting), Grosse Pointe Woods, Michigan 48236, United States

Spectrum Health Hospitals-Cook Research Dept. (No longer recruiting), Grand Rapids, Michigan 49503, United States

Great Lakes Cancer Center Management Specialties, Grosse Point Woods, Michigan 48236, United States

Henry Ford Health System, Detroit, Michigan 48202, United States

St. Barnabas Health Care Center, Newark, New Jersey 07112, United States

Roswell Park Cancer Institute, Buffalo, New York 14263, United States

Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1082, United States

Cleveland Clinic Foundation-Hemoatology/Oncology, Cleveland, Ohio 44195-001, United States

Thomas Jefferson University Medical College, Philadelphia, Pennsylvania 19107, United States

Baptist Clinical Research Center, Memphis, Tennessee 38120, United States

Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States

Starting date: July 2004
Ending date: October 2005
Last updated: July 18, 2007