Study of Deferasirox Relative to Subcutaneous Deferoxamine in Sickle Cell Disease Patients

Phase 2

Completed

Conditions: Sickle Cell Disease
Iron Overload
Hemolytic Anemia

Interventions: Drug: Deferasirox (ICL670)
Drug: Deferoxamine (DFO)

Registration Number: NCT00110617

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: This study will examine the long-term safety and efficacy of Deferasirox in patients with sickle cell disease and iron overload from repeated blood transfusions.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 212

Inclusion Criteria

Age greater than or equal to 2 years
Male or female patients with sickle cell disease (SS, SC, SD, Sβo or Sβ+ thalassemia)
Iron overload from repeated blood transfusion, as defined by one of the following:
1. For patients > 16 years old receiving simple transfusions: lifetime history of receipt of at least 120 ml/kg or 30 adult units of packed red blood cells, OR
2. For patients ≤ 16 years old receiving simple transfusions: lifetime history of receipt of at least 120 ml/kg of packed red blood cells, OR
3. For all patients receiving exchange transfusions in the absence of a previous attempt to achieve negative iron balance: lifetime performance of at least 20 procedures, OR
4. For all patients: liver iron content ≥ 7 mg Fe/g dry weight as measured by biopsy, Magnetic Resonance Imaging (MRI), or magnetic susceptibility performed within 3 months prior to entry into screening
For entry into the screening period: serum ferritin of ≥ 1000 µg/mL on at least two occasions during the prior year obtained in the absence of concomitant infection.
Body weight > 10 kg
No known allergy or contraindication to the administration of deferoxamine
Ability to comply with all study-related procedures, medications, and evaluations
Sexually active pre-menopausal female patients must use double-barrier contraception, oral contraceptive plus barrier contraceptive, or must have undergone clinically documented total hysterectomy and/or oophorectomy, tubal ligation or be postmenopausal defined by amenorrhea for at least 12 months.
Written informed consent by the patient or for pediatric patient's consent of the patient's legal guardian. The definition of the term 'pediatric' for enrollment and study conduct will be in accordance with the local legislation.

Exclusion Criteria

Serum creatinine above the upper limit of normal
Significant proteinuria
History of nephrotic syndrome
Alanine aminotransferase (ALT) ≥ 250 U/L at screening
Clinical evidence of active hepatitis B or hepatitis C
History of HIV
Fever or other signs/symptoms of infection within 10 days prior to the screening visit
Uncontrolled systemic hypertension
History of Myocardial Infarction, Congestive Heart Failure or unstable cardiac disease not controlled by standard medical therapy
Clinically relevant cataract or a previous history of clinically relevant ocular toxicity related to iron chelation
Presence of a surgical or medical condition that might significantly alter the absorption, distribution, metabolism or excretion of any study drug
History of drug or alcohol abuse within the 12 months prior to enrollment
Pregnant or breast feeding patients
Patients treated with systemic investigational drug within 4 weeks prior or with topical investigational drug 7 days prior to the screening visit
Randomization in a previous clinical trial involving ICL670

Other protocol-related inclusion / exclusion criteria may apply.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Deferasirox (ICL670)	Deferasirox (ICL670)	Deferasirox (ICL670) 20 mg/kg orally once daily for 104 weeks.
Deferoxamine (DFO) then ICL670	Deferasirox (ICL670)	Deferoxamine (DFO) subcutaneously for a weekly dose of 175 mg/kg for 24 weeks then crossed over to receive Deferasirox (ICL670) orally 20 mg/kg for a total of 104 weeks on therapy.
Deferoxamine (DFO) then ICL670	Deferoxamine (DFO)	Deferoxamine (DFO) subcutaneously for a weekly dose of 175 mg/kg for 24 weeks then crossed over to receive Deferasirox (ICL670) orally 20 mg/kg for a total of 104 weeks on therapy.

Primary Outcome Measures

Name	Time	Method
The Number of Participants With Adverse Events (AEs) in the First 24 Weeks of Treatment	24 Weeks	The number of participants with Adverse Events (AEs) overall and according to Medical Dictionary for Regulatory Activities (MedDRA) preferred term greater than or equal to 5% participants in any group by treatment in the first 24 weeks.

Secondary Outcome Measures

Name	Time	Method
Absolute Change in Serum Ferritin From Baseline to Week 24	Baseline, 24 Weeks	Absolute change from baseline serum ferritin after 24 weeks of treatment with Deferasirox (ICL670) and absolute change from baseline serum ferritin after 24 weeks of treatment with Deferoxamine. Means were adjusted for the amount of transfused blood.
Absolute Change in Serum Ferritin After Start of Treatment With Deferasirox (ICL670) to Week 24 and to Week 52	Start of Deferasirox (ICL670) treatment, 24 Weeks, 52 Weeks	Absolute change in serum ferritin after start of treatment with Deferasirox (ICL670) to week 24 and the absolute change in serum ferritin after start of treatment with Deferasirox (ICL670) to week 52 for the Deferasirox treatment group and the Deferoxamine then Deferasirox treatment group. Means were adjusted for the amount of transfused blood.
Absolute Change in Serum Ferritin After Start of Treatment With Deferasirox (ICL670) to Week 104	Start of Deferasirox (ICL670) treatment, 104 Weeks	Absolute change in serum ferritin after start of treatment with Deferasirox (ICL670) to week 104 for the Deferasirox treatment group. Means were adjusted for the amount of transfused blood.

Trial Locations

Locations (58): Pennsylvania Oncology/Hematology
🇺🇸
Philadelphia, Pennsylvania, United States
Children's Healthcare of Atlanta at Scottish Rite
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Atlanta, Georgia, United States
Children's Hospital of Pittsburgh
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Pittsburgh, Pennsylvania, United States
Hillman Cancer Center
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Pittsburgh, Pennsylvania, United States
University of Illinois at Chicago
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Chicago, Illinois, United States
Children's Memorial Hospital
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Chicago, Illinois, United States
Brigham and Woman's Hospital/Harvard Medical School
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Boston, Massachusetts, United States
Texas Children's Hospital/Baylor College of Medicine
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Houston, Texas, United States
Children's National Medical Center
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Washington, District of Columbia, United States
Virginia Commonwealth University
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Richmond, Virginia, United States
St. Jude's Children Research Hospital
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Memphis, Tennessee, United States
Columbia University
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New York, New York, United States
New York Methodist Hospital
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Brooklyn, New York, United States
Children's Hospital Oakland
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Oakland, California, United States
Miami Children's Hospital
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Miami, Florida, United States
Backus Children's Hospital
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Savannah, Georgia, United States
Pediatric Sickle Cell Program/James Whitcomb Riley Hospital for Children
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Indianapolis, Indiana, United States
Adult Sickle Cell Clinic
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Augusta, Georgia, United States
University of South Alabama Medical Center
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Mobile, Alabama, United States
Howard University Hospital
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Washington, District of Columbia, United States
Emory University School of Medicine
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Atlanta, Georgia, United States
Tulane University Sickle Cell Center
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New Orleans, Louisiana, United States
St. Jude Children's Hospital Affiliate
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Baton Rouge, Louisiana, United States
Children's Hospital of Philadelphia
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Philadelphia, Pennsylvania, United States
Carolinas Medical Transplant Center
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Charlotte, North Carolina, United States
Hopital Ste-Justine
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Montreal, Quebec, Canada
Drexel University College of Medicine
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Philadelphia, Pennsylvania, United States
Santee Hematology/Oncology
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Sumter, South Carolina, United States
Children's Hospital of the King's Daughter
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Norfolk, Virginia, United States
Medical College of Virginia
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Richmond, Virginia, United States
University of Alabama Pediatric Hematology/Oncology
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Birmingham, Alabama, United States
Tampa Children's Hospital at St Joseph's
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Tampa, Florida, United States
University of Alabama Medical center
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Birmingham, Alabama, United States
Tampa Children's Hospital at St. Joseph's
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Tampa, Florida, United States
H. Lee Muffit Cancer Center and Research Institute/James A. Haley Veterans Hospital
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Tampa, Florida, United States
Karmanos Cancer Institute
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Detroit, Michigan, United States
University of Cincinnati
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Cincinnati, Ohio, United States
Children's Hospital Medical Center
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Cincinnati, Ohio, United States
The University of Oklahoma
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Oklahoma City, Oklahoma, United States
Scott and White Memorial Hospital & Clinics
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Temple, Texas, United States
University of South Alabama
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Mobile, Alabama, United States
Children's Hospital Boston
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Boston, Massachusetts, United States
Jefferson University
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Philadelphia, Pennsylvania, United States
Weill Medical College of Cornell University
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New York, New York, United States
University of Alberta
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Edmonton, Alberta, Canada
Sickle Cell Center, Montefiore Hospital
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Bronx, New York, United States
Center for Cancer and Blood Disorders
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Washington, District of Columbia, United States
Children's Hospital
🇺🇸
Boston, Massachusetts, United States
Cooks Children's Hospital
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Fort Worth, Texas, United States
SUNY Downstate Medical Center
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Brooklyn, New York, United States
Liberty Hematology Oncology Center
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Columbia, South Carolina, United States
Loma Linda University Medical Center
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Loma Linda, California, United States
Washington University School of Medicine
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St. Louis, Missouri, United States
University of Michigan
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Ann Arbor, Michigan, United States
LSU Health Sciences Center/Carroll W. Feist Professor of Cancer Research
🇺🇸
Shreveport, Louisiana, United States
Palmetto Health Clinical Trials
🇺🇸
Columbia, South Carolina, United States
St Jude's Children's Research Hospital
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Memphis, Tennessee, United States
The Ottawa Hospital
🇨🇦
Ottawa, Ontario, Canada