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

This study has been completed.
Sponsor:
Information provided by:
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT00086099
First received: June 23, 2004
Last updated: January 28, 2009
Last verified: January 2009
  Purpose

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 Intervention Phase
Leukemia
Acute Myeloid Leukemia
Drug: Idarubincin and Amufostine (Ethyol)
Drug: Idarubincin
Phase 1
Phase 2

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

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • Clinically significant hematologic and non-hematologic toxicities associated with idarubicin administration [ Time Frame: 30 days after last dose ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: 30 days after last dose ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Duration of Complete Remission [ Time Frame: Estimated by analysis cohort using Kaplan-Mier Method ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: 19 mos. after last patient entered or randomized (whichever was earlier). ] [ Designated as safety issue: Yes ]

Enrollment: 54
Study Start Date: July 2004
Study Completion Date: February 2006
Primary Completion Date: December 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Idarubicin plus amifostine
Drug: Idarubincin and Amufostine (Ethyol)
Starting doses of Idarubincin(12,18 mg/m2 to 21 mg/m2), ara-C, plus amofostine (N-36)
Experimental: 2
Idarubincin
Drug: Idarubincin
Idarubincin (12mg/m2) and ara-C(N-18)

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00086099

Locations
United States, California
Scripps Cancer Center
San Diego, California, United States, 92121
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Indiana
Cancer Care Center
New Albany, Indiana, United States, 47150
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
Spectrum Health Hospitals-Cook Research Dept. (No longer recruiting)
Grand Rapids, Michigan, United States, 49503
Great Lakes Cancer Center Management Specialties
Grosse Point Woods, Michigan, United States, 48236
Cancer Management Specialists (No longer Recruiting)
Grosse Pointe Woods, Michigan, United States, 48236
United States, New Jersey
St. Barnabas Health Care Center
Newark, New Jersey, United States, 07112
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
United States, North Carolina
Wake Forest University School of Medicine
Winston-Salem, North Carolina, United States, 27157-1082
United States, Ohio
Cleveland Clinic Foundation-Hemoatology/Oncology
Cleveland, Ohio, United States, 44195-001
United States, Pennsylvania
Thomas Jefferson University Medical College
Philadelphia, Pennsylvania, United States, 19107
United States, Tennessee
Baptist Clinical Research Center
Memphis, Tennessee, United States, 38120
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Israel
Rambam Medical Center
Haifa, Israel, 31096
Rabin Medical Center
Petach Tikva, Israel, 49100
Kaplan Med. Center
Rehovot, Israel, 76100
Sheba Medical Center
Tel Hasomer, Israel, 52620
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: Dirk J. Reitsma, M.D. MedImmune LLC
  More Information

No publications provided

Responsible Party: Dirk J. Reitsma, M.D., MedImmune LLC
ClinicalTrials.gov Identifier: NCT00086099     History of Changes
Other Study ID Numbers: MI-CP103
Study First Received: June 23, 2004
Last Updated: January 28, 2009
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Idarubicin
Amifostine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Protective Agents
Protective Agents
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on July 24, 2014