The purpose of this study is to determine if the new orally active iron chelator, ICL670, is as safe as deferoxamine in preventing accumulation of iron in the body while a patient is undergoing repeated blood transfusions.

Condition	Treatment or Intervention	Phase
Anemia, Sickle Cell	Drug: ICL670  Drug: deferoxamine	Phase II

Further Study Details: 

Expected Total Enrollment:  170

Patients who require repeated blood transfusions accumulate iron in the body as blood cells contain iron and there is no natural body mechanism to eliminate it. After a while the iron levels get high enough to be toxic to the body. The current therapy of choice is deferoxamine which does a good job of removing excess iron, but is difficult to administer. Deferoxamine requires subcutaneous (under the skin) infusions over 4 to 8 hours nightly 3 to 7 nights per week. In addition to the need to wear an infusion pump nightly, adverse reactions around the site of the injection are frequent.

Ages Eligible for Study:  2 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Age greater than or equal to 2 years
• Sickle cell disease patients already treated with or suitable for treatment with deferoxamine 20 to 40 mg/kg/day
• Serum ferritin greater than 1000 mg/ml
• Liver iron content greater than 2 mg iron/g dw assessed by means of superconducting quantum interference device (SQUID) for patients who receive simple transfusions and greater than 5 mg iron/ g dw for patients who receive exchange transfusions or who have a history of intermittent blood transfusion.
• Regular transfusion aimed at maintaining % Hb A above 50% or a previous history of simple transfusion being the recipient of at least 20 units of packed red blood cells.

Exclusion Criteria:

• Chronic anemias other than sickle cell disease
• Documented toxicity to deferoxamine
• Elevated liver enzymes in the year preceeding enrollment
• Active hepatitis B or hepatitis C
• HIV seropositivity
• Elevated serum creatinine or significant proteinuria
• History of nephrotic syndrome
• Uncontrolled systemic hypertension
• Fever and other signs/symptoms of infection within 10 days prior to the start of the study
• Presence of clinically relevant cataract or previous history of clinically relevant ocular toxicity related to iron chelation
• Second or third degree AV block, clinically relevant Q-T interval prolongation, or patients requiring digoxin or other drugs that prolong the Q-T interval (other than beta-adrenergic receptor blocking agents).
• Diseases (cardiovascular, renal, hepatic, etc.) that would prevent the patient from undergoing any of the treatment options
• Psychiatric or addictive disorders that would prevent the patient from giving informed consent
• History of drug or alcohol abuse within the 12 months prior to the study
• Pregnant or breast feeding patients
• Patients treated with systemic investigational drugs within 4 weeks or topical investigational drugs within 7 days before the start of the study
• Patients who require concomitant therapy with hydroxyurea
• Any surgical or medical condition that might significantly alter the absorption, distribution, metabolism or excretion of any drug, such as gastrointestinal disease or major surgery, renal disease, difficulty voiding or urinary obstruction, or impaired pancreatic function
• Non-compliant or unreliable patients
• Patients unable to undergo any study procedures such as the hearing or eye tests, or the liver echocardiography
• Patients unable to undergo SQUID examination

Alabama
      U. of S. Alabama Medical Center, Mobile,  Alabama,  36604,  United States
California
      Children's Hospital & Research Center, Oakland,  California,  94609,  United States
      Children's Hospital Los Angeles, Los Angeles,  California,  90027,  United States
      Loma Linda University Medical Center, Loma Linda,  California,  92354,  United States
Colorado
      Colorado Sickle Cell Treatment and Research Center, Denver,  Colorado,  80262,  United States
District of Columbia
      Howard University Hospital, Washington,  District of Columbia,  20059,  United States
Florida
      Tampa Children's Hospital at St Joseph's, Tampa,  Florida,  33607,  United States
Georgia
      Adult Sickle Cell Clinic, Medical College of Georgia, Augusta,  Georgia,  30912,  United States
      Georgia Comprehensive Sickle cell Center, Grady Hospital, Atlanta,  Georgia,  30335,  United States
Illinois
      University of Illinois at Chicago, Chicago,  Illinois,  60612,  United States
      Children's Memorial Hospital, Chicago,  Illinois,  60614,  United States
Louisiana
      Tulane University Sickle Cell Center, New Orleans,  Louisiana,  70112,  United States
      Children's Hospital, Department of Hematology/Oncology, New Orleans,  Louisiana,  70118,  United States
Massachusetts
      Boston Medical Center, Boston,  Massachusetts,  02118,  United States
      Children's Hospital Boston, Division of Hematology/Oncology, Boston,  Massachusetts,  02115,  United States
Michigan
      Karmanos Cancer Institute, Detroit,  Michigan,  48201,  United States
New York
      NY Methodist Hospital, Brooklyn,  New York,  11215,  United States
      Sickle Cell Center, Montefiore Hospital, Bronx,  New York,  10467,  United States
      U. Of Rochester Medical Center, Rochester,  New York,  14642,  United States
      Weill Medical College of Cornell University, New York,  New York,  10021,  United States
North Carolina
      Wake Forest University School of Medicine, Winston Salem,  North Carolina,  United States
Ohio
      Children's Hospital Medical Center, Cincinnati,  Ohio,  45229,  United States
      James Cancer Hospital, Columbus,  Ohio,  43210,  United States
      Barrett Center, University of Cincinnati, Cincinnati,  Ohio,  45219,  United States
Pennsylvania
      Children's Hospital of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States
      Penn State Milton S Hershey Medical Center, Hershey,  Pennsylvania,  17033,  United States
      Children's Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States
South Carolina
      Santee Hematology/Oncology, Sumter,  South Carolina,  29150,  United States
      Palmetto Health Clinical Trials, Columbia,  South Carolina,  29203,  United States
      Liberty Hematology Oncology Center, Columbia,  South Carolina,  29203,  United States
Texas
      Baylor College of Medicine, Houston,  Texas,  77030,  United States
      Scott and White Memorial Hospital & Clinics, Temple,  Texas,  76508,  United States
      Texas Children's Hospital/Baylor College of Medicine, Houston,  Texas,  77030,  United States
Virginia
      Children's Hospital of the King's Daughter, Norfolk,  Virginia,  23507,  United States

Study ID Numbers:  CICL670A0109
Record last reviewed:  November 2004
Last Updated:  December 1, 2004
Record first received:  August 11, 2003
ClinicalTrials.gov Identifier:  NCT00067080
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08