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

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

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.

Study Overview

• Status: Completed
• Conditions: Iron Overload; Sickle Cell Disease; Hemolytic Anemia
• Intervention / Treatment: Drug: Deferasirox (ICL670); Drug: Deferoxamine (DFO)

• Study Type: Interventional
• Enrollment (Actual): 212
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2H7
      • University of Alberta
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • Hôpital Ste-Justine
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama Medical Center
    • Birmingham, Alabama, United States, 35233
      • University of Alabama Pediatric Hematology/Oncology
    • Mobile, Alabama, United States, 36604
      • University of South Alabama Medical Center
    • Mobile, Alabama, United States, 36617
      • University of South Alabama
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Medical Center
    • Oakland, California, United States, 94609
      • Children's Hospital Oakland
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
    • Washington, District of Columbia, United States, 20010-2970
      • Center for Cancer and Blood Disorders
    • Washington, District of Columbia, United States, 20059
      • Howard University Hospital
  • Florida
    • Miami, Florida, United States, 33155
      • Miami Children's Hospital
    • Tampa, Florida, United States, 33607-6387
      • Tampa Children's Hospital at St Joseph's
    • Tampa, Florida, United States, 33607-6387
      • Tampa Children's Hospital at St. Joseph's
    • Tampa, Florida, United States, 33612
      • H. Lee Muffit Cancer Center and Research Institute/James A. Haley Veterans Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Children's Healthcare of Atlanta at Scottish Rite
    • Atlanta, Georgia, United States, 30303
      • Emory University School of Medicine
    • Augusta, Georgia, United States, 30912-3128
      • Adult Sickle Cell Clinic
    • Savannah, Georgia, United States, 31403
      • Backus Children's Hospital
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
    • Chicago, Illinois, United States, 60614-3394
      • Children's Memorial Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Pediatric Sickle Cell Program/James Whitcomb Riley Hospital for Children
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • St. Jude Children's Hospital Affiliate
    • New Orleans, Louisiana, United States, 70118
      • Children's Hospital
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Sickle Cell Center
    • Shreveport, Louisiana, United States, 71130
      • LSU Health Sciences Center/Carroll W. Feist Professor of Cancer Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Children's Hospital Boston
    • Boston, Massachusetts, United States, 02115
      • Children's Hospital
    • Boston, Massachusetts, United States, 02115
      • Brigham and Woman's Hospital/Harvard Medical School
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0238
      • University of Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • Bronx, New York, United States, 10467-2490
      • Sickle Cell Center, Montefiore Hospital
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate Medical Center
    • Brooklyn, New York, United States, 11215
      • New York Methodist Hospital
    • New York, New York, United States, 10032
      • Columbia University
    • New York, New York, United States, 10021
      • Weill Medical College of Cornell University
  • North Carolina
    • Charlotte, North Carolina, United States, 28232
      • Carolinas Medical Transplant Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
    • Cincinnati, Ohio, United States, 72764
      • Children's Hospital Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • The University of Oklahoma
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-4399
      • Children's Hospital of Philadelphia
    • Philadelphia, Pennsylvania, United States, 19106
      • Pennsylvania Oncology/Hematology
    • Philadelphia, Pennsylvania, United States, 19107
      • Jefferson University
    • Philadelphia, Pennsylvania, United States, 19134-1095
      • Drexel University College of Medicine
    • Pittsburgh, Pennsylvania, United States, 15213
      • Children's Hospital of Pittsburgh
    • Pittsburgh, Pennsylvania, United States, 15232
      • Hillman Cancer Center
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Liberty Hematology Oncology Center
    • Columbia, South Carolina, United States, 29203
      • Palmetto Health Clinical Trials
    • Sumter, South Carolina, United States, 29150
      • Santee Hematology/Oncology
  • Tennessee
    • Memphis, Tennessee, United States, 38105-2794
      • St Jude's Children's Research Hospital
    • Memphis, Tennessee, United States, 38105
      • St. Jude's Children Research Hospital
  • Texas
    • Fort Worth, Texas, United States, 76104-2724
      • Cooks Children's Hospital
    • Houston, Texas, United States, 77030-2399
      • Texas Children's Hospital/Baylor College of Medicine
    • Temple, Texas, United States, 76508
      • Scott and White Memorial Hospital & Clinics
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Children's Hospital of The King's Daughter
    • Richmond, Virginia, United States, 23298-0306
      • Medical College of Virginia
    • Richmond, Virginia, United States, 23298-0646
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Deferasirox (ICL670); Deferasirox (ICL670) 20 mg/kg orally once daily for 104 weeks.	Drug: Deferasirox (ICL670); Deferasirox was provided in 125 mg, 250 mg, and 500 mg dispersible tablets and was administered orally at an initial dose of 20 mg/kg/day.
Experimental: Deferoxamine (DFO) then 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.	Drug: Deferasirox (ICL670); Deferasirox was provided in 125 mg, 250 mg, and 500 mg dispersible tablets and was administered orally at an initial dose of 20 mg/kg/day.; Drug: Deferoxamine (DFO); Deferoxamine was supplied in vials of 500 mg and 2000 mg administered subcutaneously for a weekly dose of 175 mg/kg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Participants With Adverse Events (AEs) in the First 24 Weeks of Treatment	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.	24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change in Serum Ferritin From Baseline to Week 24	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.	Baseline, 24 Weeks
Absolute Change in Serum Ferritin After Start of Treatment With Deferasirox (ICL670) to Week 24 and to Week 52	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.	Start of Deferasirox (ICL670) treatment, 24 Weeks, 52 Weeks
Absolute Change in Serum Ferritin After Start of Treatment With Deferasirox (ICL670) to Week 104	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.	Start of Deferasirox (ICL670) treatment, 104 Weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: May 10, 2005
• First Submitted That Met QC Criteria: May 10, 2005
• First Posted (Estimate): May 11, 2005

Study Record Updates

• Last Update Posted (Estimate): May 26, 2011
• Last Update Submitted That Met QC Criteria: May 23, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: Sickle Cell Disease; Iron Overload; Blood Transfusions; Iron Overload from Repeated Blood Transfusions
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Iron Metabolism Disorders; Anemia, Hemolytic, Congenital; Hemoglobinopathies; Iron Overload; Anemia, Sickle Cell; Anemia, Hemolytic; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Siderophores; Deferasirox; Deferoxamine
• Other Study ID Numbers: CICL670A2201