Please select the eligibility criteria that correspond to the clinical trial below.
Title: Multicentre, Randomised, Open Label, Non-inferiority Trial to Evaluate the Efficacy and Safety of Deferiprone Compared to Deferasirox in Patients Aged From 1 Month to Less Than 18 Years Affected by Transfusion Dependent Haemoglobinopathies
Brief Summary: Multicentre, randomised, open label, non-inferiority active-controlled trial to evaluate efficacy and safety of a 12-months treatment with deferiprone (DFP) at dose of 75-100 mg/kg/day versus deferasirox (DFX) at dose of 20-40 mg/kg/day in paediatric patients (1 month \< 18 years old) affected by hereditary haemoglobinopathies and requiring frequent transfusions and chelation.


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 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
C: 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
D: Inclusion Criteria:

* Patients of both genders aged from 1 month up to less than 18 years at the time of enrolment
* Patients affected by any hereditary haemoglobinopathy requiring chronic transfusion therapy and chelation, including but not limited to thalassemia syndromes and sickle cell disease
* Patients on current treatment with deferoxamine (DFO) or DFX or DFP in a chronic transfusion program receiving at least 150 mL/kg/year of packed red blood cells (corresponding approximately to 12 transfusions);
* For patients naïve to chelation treatment: patients that have received at least 150 mL/kg of packed red blood cells (corresponding to approximately 12 transfusions) in a chronic transfusion program and with serum ferritin levels ≥ 800 ng/mL;
* Until availability of results from the PK Study (Study DEEP-1, EudraCT n. 2012-000658-67) for patients aged from 1 month to less than 6 years: known intolerance or contraindication to DFO;
* Written informed consent and patient's informed assent, relating to his/her comprehension abilities and level of maturity

Exclusion Criteria:

* Patients with intolerance or known contraindication to either DFP or DFX
* Patients receiving DFX at a dose \> 40 mg/kg/day or DFP at a dose \> 100 mg/kg/day at screening
* Platelet count \<100.000/mm3 during the run-in phase
* Absolute neutrophils count \<1.500/mm3 during the run-in phase
* Hb levels lower than 8g/dL during the run-in phase
* Evidence of abnormal liver function
* Iron overload from causes other than transfusional haemosiderosis
* Severe heart dysfunction secondary to iron overload
* Serum creatinine level \> ULN (Upper Limit of Normal) for age during the run-in phase
* History of significant medical or psychiatric disorder
* The patient has received another investigational drug within 30 days prior to this clinical trial
* Fever and other signs/symptoms of infection in the 10 days before baseline assessment
* Concomitant use of trivalent cation-dependent medicinal products such as aluminium-based antacids
* Positive test for β-HCG (Human chorionic gonadotropin) and lactating female patients

Answer: D