Please select the eligibility criteria that correspond to the clinical trial below.
Title: The Efficacy and Safety of Ferriprox® for the Treatment of Transfusional Iron Overload in Patients With Sickle Cell Disease or Other Anemias
Brief Summary: This research is being done so that we can look at the safety and efficacy of deferiprone in people with sickle cell disease or other anemias. Deferiprone is a drug that removes iron from the body. We will be comparing deferiprone with deferoxamine, another drug that removes iron from the body.


Options:
A: Key Inclusion Criteria:

* Male and female patients aged ≥ 10 years
* Patients with transfusion-dependent thalassemia and iron overload, requiring deferasirox DT at doses of ≥ 30 mg/kg/day as per the investigator's decision OR Patients with very low, low or intermediate (int) risk myelodysplastic syndrome (MDS) and iron overload, requiring deferasirox DT at doses of ≥ 20 mg/kg/day as per the investigator's decision.
* History of transfusion of at least 20 PRBC units and anticipated to be transfused with at least 8 units of PRBCs annually during the study
* Serum ferritin \> 1000 ng/mL, measured at screening Visit 1 and screening Visit 2 (the mean value will be used for eligibility criteria).

Key Exclusion Criteria:

* Creatinine clearance below the contraindication limit in the locally approved prescribing information. Creatinine clearance will be estimated from serum creatinine at screening Visit 1 and screening Visit 2 and the mean value will be used for eligibility criteria.
* Serum creatinine \> 1.5 xULN at screening measured at screening Visit 1 and screening Visit 2 (the mean value will be used for eligibility criteria).
* ALT (SGPT) \> 5xULN, unless LIC confirmed as \>10 mg Fe/dw within 6 months prior to screening visit 1.
* Significant proteinuria as indicated by a urinary protein/creatinine ratio \> 0.5 mg/mg in a non-first void urine sample at screening Visit 1 or screening Visit 2.
* Patients with significant impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral deferasirox (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
* Liver disease with severity of Child-Pugh Class B or C
B: 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
C: Inclusion Criteria:

* Beta-thalassemia patients already treated with or suitable for treatment with deferoxamine 20 to 40 mg/kg/day
* Liver iron content greater than 2 mg iron/g dw as measured by liver biopsy
* Need for regular transfusions 8 or more times per year

Exclusion Criteria:

* Non-transfusional iron overload or transfusion-dependent anemias other than beta-thalassemia.
* Documented toxicity to deferoxamine
* Elevated liver enzymes in the year preceeding enrollment
* Active hepatitis B or hepatitis C
* HIV seropositivity
* Elevated serum creatinine or significant proteinuria
* History of nephrotic syndrome
* Uncontrolled systemic hypertension
* Fever and other signs/symptoms of infection within 10 days prior to start of the study
* Presence of clinically relevant cataract or previous history of clinically relevant ocular toxicity related to iron chelation
* Second or third degree AV block, clinically relevant Q-T interval prolongation, or patients requiring digoxin or other drugs that prolong the Q-T interval
* Diseases (cardiovascular, renal, hepatic, etc.)that would prevent the patient from undergoing any of the treatment options
* Psychiatric or additive disorders that would prevent the patient from giving informed consent
* History of drug or alcohol abuse within the 12 months prior to the study
* Pregnant or breast feeding patients
* Patients treated with systemic investigational drugs within 4 weeks or topical investigational drugs within 7 days before the start of the study
* Any surgical or medical condition that might significantly alter the absorption, distribution, metabolism or excretion of any drug, such as gastrointestinal disease or major surgery, renal disease, difficulty voiding or urinary obstruction, or impaired pancreatic function.
* Non-compliant or unreliable patients.
* Patients unable to undergo any study procedures such as the hearing or eye tests, or the liver echocardiography.
* Inability to undergo a liver biopsy.
* Patients that would need a dose of ICL670 less than 125 mg per day.
D: Inclusion Criteria:

1. Young beta thalassemia major patients (diagnosed by HPLC, CBC) who started transfusion therapy who received 5-7transfusions or less, aged more than 6 months.
2. Pre-transfusional Hb should be \>9 g/dL.
3. Serum ferritin should be ≤ 500ng/ml, transferrin saturation ≤ 50%.

Exclusion Criteria:

* 1. Beta thalassemia intermedia patients, patients with other transfusion dependent anemias (myelodysplasia, other chronic hemolytic anemias , pure red cell aplasia , aplastic anemia ) 2. Patients with levels of ALT \>5 the upper limit of normal (ULN), serum creatinine \> ULN on 2 measurements.

  3. Patients with history of agranulocytosis \[absolute neutrophil count (ANC) \<0.5×109/L\].

  4. Non complaint patients acknowledged by reviewing the patient's records.

Answer: B