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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00086099
• Other study ID #: MI-CP103
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: June 23, 2004
• Last updated: January 28, 2009
• Start date: July 2004
• Est. completion date: February 2006

Study information

• Verified date: January 2009
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: February 2006
• Est. primary completion date: December 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Idarubincin and Amufostine (Ethyol)
Starting doses of Idarubincin(12,18 mg/m2 to 21 mg/m2), ara-C, plus amofostine (N-36)
• Idarubincin
Idarubincin (12mg/m2) and ara-C(N-18)

Locations

Country	Name	City	State
Israel	Rambam Medical Center	Haifa
Israel	Rabin Medical Center	Petach Tikva
Israel	Kaplan Med. Center	Rehovot
Israel	Sheba Medical Center	Tel Hasomer
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Rush University Medical Center	Chicago	Illinois
United States	Cleveland Clinic Foundation-Hemoatology/Oncology	Cleveland	Ohio
United States	Henry Ford Health System	Detroit	Michigan
United States	Spectrum Health Hospitals-Cook Research Dept. (No longer recruiting)	Grand Rapids	Michigan
United States	Great Lakes Cancer Center Management Specialties	Grosse Point Woods	Michigan
United States	Cancer Management Specialists (No longer Recruiting)	Grosse Pointe Woods	Michigan
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Baptist Clinical Research Center	Memphis	Tennessee
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Cancer Care Center	New Albany	Indiana
United States	St. Barnabas Health Care Center	Newark	New Jersey
United States	Thomas Jefferson University Medical College	Philadelphia	Pennsylvania
United States	Scripps Cancer Center	San Diego	California
United States	Wake Forest University School of Medicine	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Countries where clinical trial is conducted

United States,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinically significant hematologic and non-hematologic toxicities associated with idarubicin administration		30 days after last dose	Yes
Primary	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		30 days after last dose	Yes
Secondary	Duration of Complete Remission		Estimated by analysis cohort using Kaplan-Mier Method	No
Secondary	Overall Survival		19 mos. after last patient entered or randomized (whichever was earlier).	Yes