Please select the eligibility criteria that correspond to the clinical trial below.
Title: An Extension Study of Iron Chelation Therapy With Deferasirox (ICL670)in β-thalassemia Patients With Transfusional Iron Overload
Brief Summary: A 1-year randomized Phase III core trial (NCT00061750) using deferoxamine as the comparator was conducted to investigate the efficacy of deferasirox in regularly transfused patients with β-thalassemia 2 years of age and older. Patients who successfully completed this main trial may continue in this extension trial to receive chelation therapy with deferasirox for an additional 4 years.

The objective of this study is to assess the efficacy and long-term safety of deferasirox in regularly transfused patients with β-thalassemia 2 years of age and older.


Options:
A: Inclusion Criteria:

1. Male or female ≥ 2 years of age;
2. Have sickle cell disease (confirmed by Hb electrophoresis or more specific tests) or other conditions with iron overload from repeated blood transfusions (see exclusion criteria for exceptions);
3. Baseline LIC \>7 mg/g dw (measured by MRI);
4. Patients who have received no less than 20 transfusions of RBCs;
5. Patients who have received at least 1 transfusion per year in the last 2 years and who are expected to have a continuing requirement (based on Investigator's judgement) during the duration of the trial

Exclusion Criteria:

1. Thalassemia syndromes;
2. Myelodysplastic syndrome (MDS) or myelofibrosis;
3. Diamond Blackfan anemia;
4. Primary bone marrow failure;
5. Baseline LIC \>30 mg/g dw (measured by MRI);
6. Unable or unwilling to undergo a 7 day washout period if currently being treated with deferiprone or deferoxamine or deferasirox;
7. Previous discontinuation of treatment with deferiprone or deferoxamine due to adverse events;
8. History or presence of hypersensitivity or idiosyncratic reaction to deferiprone or deferoxamine;
9. Treated with hydroxyurea within 30 days;
10. History of malignancy;
11. Evidence of abnormal liver function (serum ALT level(s) \> 5 times upper limit of normal at screening or creatinine levels \>2 times upper limit of normal at screening);
12. A serious, unstable illness, as judged by the Investigator, during the past 3 months before screening/baseline visit including but not limited to: hepatic, renal, gastro-enterologic, respiratory, cardiovascular, endocrinologic, neurologic or immunologic disease;
13. Clinically significant abnormal 12-lead ECG findings;
14. Cardiac MRI T2\* \<10ms;
15. Myocardial infarction, cardiac arrest or cardiac failure within 1 year before screening/baseline visit;
16. Unable to undergo MRI
17. Presence of metallic objects such as artificial joints, inner ear (cochlear) implants, brain aneurysm clips, pacemakers, and metallic foreign bodies in the eye or other body areas that would prevent use of MRI imaging
B: Inclusion Criteria:

* Patients presenting with transfusion-dependent anemias (independent of underlying condition) with transfusional iron overload as shown by a serum ferritin level of ≥ 1000 ng/ml
* Patients of either gender and aged ≥ 2 years
* Female patients who have reached menarche and who are sexually active must use an effective method of contraception, or must have undergone clinically documented total hysterectomy and/or ovariectomy, or tubal ligation.

Additional Inclusion Criteria for Adult Patients:

* Written informed consent by the patient

Additional Inclusion Criteria for Pediatric Patients:

* The definition of the term "pediatric" will be in accordance with local legislation. Parents or legal guardians will be fully informed by the investigator as to the requirements of the study. The pediatric patients themselves will be informed according to their capabilities in a language and terms that they are able to understand. Written informed consent will be obtained from their parents or legal guardians on the patient's behalf in accordance with the national legislation. If capable, all patients should also personally sign their written informed assent.

Exclusion Criteria:

* Non-transfusional hemosiderosis
* Patients with clinical evidence supporting the need for intensive chelation, based on the investigator's judgment
* Patients with mean levels of alanine aminotransferase (ALT) \> 300 U/l
* Patients with uncontrolled systemic hypertension
* Patients with serum creatinine above the upper limit of normal (ULN)
* Significant proteinuria as indicated by a urinary protein/creatinine ratio \> 0.5 (mg/mg) in second-voiding urine samples taken at both visits 1 and 2. A third sample is to be taken from patients in whom one ratio is \> 0.5 (mg/mg) and one is ≤ 0.5 (mg/mg) and patients in whom the urinary protein/creatinine ratio is \> 0.5 (mg/mg) in two of the three determinations are also to be excluded.
* History of nephrotic syndrome
* Patients with 3rd atrioventricular (A-V) block, clinically relevant Q-T interval prolongation as well as patients requiring treatment with digoxin and similar compounds or drugs which may induce prolongation of the Q-T interval
* Patients with a previous history of clinically relevant ocular toxicity related to iron chelation
* Systemic diseases (cardiovascular, renal, hepatic, etc.) which would prevent the patient from undergoing study treatment
* Patients with psychiatric or addictive disorders which prevent them from giving their informed consent or undergoing study treatment
* Pregnant or breast feeding patients
* Patients treated with systemic investigational drugs within the past 4 weeks or topical investigational drugs within the past 7 days
* Any other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug. The investigator should be guided by evidence of any of the following:

  * history of inflammatory bowel syndrome, gastritis, ulcers, gastrointestinal or rectal bleeding;
  * history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
  * history of pancreatic injury or pancreatitis; indications of impaired pancreatic function/injury as indicated by abnormal lipase or amylase;
  * history or presence of impaired renal function as indicated by creatinine or blood urea nitrogen (BUN) values equal or above ULN;
  * history of urinary obstruction or difficulty in voiding.
* History of non-compliance to medical regimens and patients who are considered potentially unreliable and/or not cooperative
* History of drug or alcohol abuse within the 12 months prior to dosing or evidence of such abuse as indicated by the laboratory assays conducted during the run-in period
* Patients with positive test to HIV
* Life expectancy of \< 1 year

Exclusion Criteria for Pediatric Patients:

* Patient body weight which prevents the use of the smallest tablet strength (i.e. 125 mg) for proper dosing

Other protocol-defined inclusion/exclusion criteria may apply.
C: Inclusion criteria

* Patients who completed the 12-month core study (NCT00061750)
* Female patients after menarche and who were sexually active, if they used double-barrier contraception, oral contraceptive plus barrier contraceptive, or had undergone clinically documented total hysterectomy and/or ovariectomy, or tubal ligation
* Written informed consent obtained from the patient and/or legal guardian on the patient's behalf in accordance with the national legislation

Exclusion criteria

* Pregnant or breast feeding patients
* Patients with a history of non-compliance to medical regimens or those considered to be potentially unreliable
D: Inclusion Criteria:

* Iron-overloaded patients without prior iron chelation therapy as well as pretreated patients
* Age: 4 years and older
* Sex: male and female
* Written informed consent

Exclusion Criteria:

* Children \< 4 years of age
* Patients non-compliant to DFO or L1
* Patients with known DFO or L1 toxicity/intolerance
* Neutropenia (neutrophils \< 1.5 x 10exp9/L)
* Thrombocytopenia (platelets \< 100 x 10exp9/L)
* Renal, hepatic (liver enzymes 2.5x of upper normal level and higher) or decompensated heart failure
* Active viral illness currently treated with interferon-alpha/ribavirin
* Patients with repeated Yersinia infections
* HIV-positivity
* Pregnancy and nursing
* Female and male of reproductive age planning for family, sexually active but not taking adequate contraceptive precaution

Answer: C