Clinical trial NCT00110617: Study of Deferasirox Relative to Subcutaneous Deferoxamine in Sickle Cell Disease Patients
Official title: A Randomized, Open-label, Multi-center, Phase II Study to Evaluate the Safety and Efficacy of Deferasirox (ICL670) 20 mg/kg/Day Relative to Subcutaneous Deferoxamine in Sickle Cell Disease Patients With Iron Overload From Repeated Blood Transfusions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sickle Cell Disease
Iron Overload
Hemolytic Anemia
Keywords: Sickle Cell Disease
Iron Overload from Repeated Blood Transfusions
Iron Overload
Blood Transfusions
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2005-05-11
Enrollment: 212
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: The Number of Participants With Adverse Events (AEs) in the First 24 Weeks of Treatment
timeFrame: 24 Weeks
Secondary outcomes:
measure: Absolute Change in Serum Ferritin From Baseline to Week 24
timeFrame: Baseline, 24 Weeks
measure: Absolute Change in Serum Ferritin After Start of Treatment With Deferasirox (ICL670) to Week 24 and to Week 52
timeFrame: Start of Deferasirox (ICL670) treatment, 24 Weeks, 52 Weeks
measure: Absolute Change in Serum Ferritin After Start of Treatment With Deferasirox (ICL670) to Week 104
timeFrame: Start of Deferasirox (ICL670) treatment, 104 Weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Pediatric Hematology/Oncology
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama Medical center
state: Alabama
city: Mobile
country: United States
facility: University of South Alabama Medical Center
state: Alabama
city: Mobile
country: United States
facility: University of South Alabama
state: Alabama
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Oakland
country: United States
facility: Children's Hospital Oakland
state: California
city: Washington
country: United States
facility: Center for Cancer and Blood Disorders
state: District of Columbia
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Howard University Hospital
state: District of Columbia
city: Miami
country: United States
facility: Miami Children's Hospital
state: Florida
city: Tampa
country: United States
facility: Tampa Children's Hospital at St Joseph's
state: Florida
city: Tampa
country: United States
facility: Tampa Children's Hospital at St. Joseph's
state: Florida
city: Tampa
country: United States
facility: H. Lee Muffit Cancer Center and Research Institute/James A. Haley Veterans Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta at Scottish Rite
state: Georgia
city: Augusta
country: United States
facility: Adult Sickle Cell Clinic
state: Georgia
city: Savannah
country: United States
facility: Backus Children's Hospital
state: Georgia
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Pediatric Sickle Cell Program/James Whitcomb Riley Hospital for Children
state: Indiana
city: Baton Rouge
country: United States
facility: St. Jude Children's Hospital Affiliate
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University Sickle Cell Center
state: Louisiana
city: New Orleans
country: United States
facility: Children's Hospital
state: Louisiana
city: Shreveport
country: United States
facility: LSU Health Sciences Center/Carroll W. Feist Professor of Cancer Research
state: Louisiana
city: Boston
country: United States
facility: Brigham and Woman's Hospital/Harvard Medical School
state: Massachusetts
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Boston
country: United States
facility: Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Bronx
country: United States
facility: Sickle Cell Center, Montefiore Hospital
state: New York
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center
state: New York
city: Brooklyn
country: United States
facility: New York Methodist Hospital
state: New York
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Transplant Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cincinnati
country: United States
facility: Children's Hospital Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: The University of Oklahoma
state: Oklahoma
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pennsylvania Oncology/Hematology
state: Pennsylvania
city: Philadelphia
country: United States
facility: Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Drexel University College of Medicine
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Hillman Cancer Center
state: Pennsylvania
city: Columbia
country: United States
facility: Liberty Hematology Oncology Center
state: South Carolina
city: Columbia
country: United States
facility: Palmetto Health Clinical Trials
state: South Carolina
city: Sumter
country: United States
facility: Santee Hematology/Oncology
state: South Carolina
city: Memphis
country: United States
facility: St Jude's Children's Research Hospital
state: Tennessee
city: Memphis
country: United States
facility: St. Jude's Children Research Hospital
state: Tennessee
city: Fort Worth
country: United States
facility: Cooks Children's Hospital
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital/Baylor College of Medicine
state: Texas
city: Temple
country: United States
facility: Scott and White Memorial Hospital & Clinics
state: Texas
city: Norfolk
country: United States
facility: Children's Hospital of the King's Daughter
state: Virginia
city: Richmond
country: United States
facility: Medical College of Virginia
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Montreal
country: Canada
facility: Hopital Ste-Justine
state: Quebec
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: