Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized Open-label Phase III Study With Deferiprone and/or Desferrioxamine in Iron Overloaded Patients
Brief Summary: Comparison of efficacy and toxicity of the combination treatment of deferiprone and desferrioxamine with the single agent treatment of either drug


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:

* Subjects with transfusional iron overload secondary to thalassemia major , sickle cell disease showing up-trend in SF aged 6 Years or older, may participate after Approval of Ethical committee giving written informed consent.
* Subjects must have a serum ferritin greater than \>2500 ng/mL, a platelet count greater than 100,000/mm3, and a serum creatinine within the normal range.
* A woman of childbearing potential must have a negative serum pregnancy test at screening. She must use a medically acceptable form of birth control during the study and for 1 month afterward.
* The subjects must also have a level of understanding and willingness to cooperate with the confinement and procedures described in the consent form and scheduled by the study site. In addition, he/she must be able to provide voluntary written informed consent.

Exclusion Criteria:

* Subjects with a past history of agranulocytosis, history of clinically significant gastrointestinal, renal, hepatic ALT \> 10 times high normal, OR \> 50% increase of serum creatinine from basal value, pulmonary or cardiovascular disease. Patients with a history of tuberculosis, epilepsy, psychosis, glaucoma or any other condition, which in the opinion of the investigators, would jeopardize the safety of the subject or impact the validity of the study results.
* Subjects with HIV positive or have active HCV.
* A history of serious immunologic hypersensitivity to any medication, such as anaphylaxis or angioedema.
* Participation in a previous investigational drug study within the 30 days preceding screening..
* Women who are pregnant, or breast-feeding.
* Current alcohol or drug abuse.
* An inability to adhere to the designated procedures and restrictions of this protocol.
* Subjects receiving warfarin, digoxin, or anti-arrhythmic or anti-seizure medications.
* Subjects with a known allergy to Exjade or DFP that prevents chronic administration.
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 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

Answer: C