Clinical trial NCT00086099: Study Evaluating the Addition of Amifostine (Ethyol®) to Idarubicin and Cytosine Arabinoside in Older Patients With Acute Myeloid Leukemia
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Leukemia
Acute Myeloid Leukemia
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2004-06-25
Enrollment: 54
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Clinically significant hematologic and non-hematologic toxicities associated with idarubicin administration
timeFrame: 30 days after last dose
measure: 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
timeFrame: 30 days after last dose
Secondary outcomes:
measure: Duration of Complete Remission
timeFrame: Estimated by analysis cohort using Kaplan-Mier Method
measure: Overall Survival
timeFrame: 19 mos. after last patient entered or randomized (whichever was earlier).
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Scripps Cancer Center
state: California
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: New Albany
country: United States
facility: Cancer Care Center
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Hospitals-Cook Research Dept. (No longer recruiting)
state: Michigan
city: Grosse Point Woods
country: United States
facility: Great Lakes Cancer Center Management Specialties
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: Cancer Management Specialists (No longer Recruiting)
state: Michigan
city: Newark
country: United States
facility: St. Barnabas Health Care Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation-Hemoatology/Oncology
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University Medical College
state: Pennsylvania
city: Memphis
country: United States
facility: Baptist Clinical Research Center
state: Tennessee
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Rehovot
country: Israel
facility: Kaplan Med. Center
city: Tel Hasomer
country: Israel
facility: Sheba Medical Center
Study officials:
affiliation: MedImmune LLC
name: Dirk J. Reitsma, M.D.
role: STUDY_DIRECTOR
References: