Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Prospective Randomized Comparative Study of Efficacy and Safety of Combined Deferiprone (DFP) and Deferasirox Versus DFP and Desferrioxamine (DFO) Therapy in Diseases With Severe Iron Overload
Brief Summary: Interventional Allocation: Randomized Endpoint Classification: Safety/Efficacy Study of combined chelation therapy Masking: Open Label Primary Purpose: Treatment of transfusional iron overload

Primary Outcome Measures:

• The primary outcome measure is to assess efficacy in lowering serum ferritin level(the change in serum ferritin compared to baseline) with combining DFP and deferasirox compared to combined DFP and DFO in conditions with severe chronic iron overload; showing an up-trend of SF over previous 12 months on single chelator.

Secondary Outcome Measures:

• The secondary outcome measure is to determine the number of patients who will develop adverse events in order to assess safety upon administering the drugs in combination (DFP and DFX) compared to the combination of DFO and DFP.


Options:
A: Inclusion Criteria for People with Thalassemia:

* Thalassemia, as documented by clinical diagnosis, including the following types:

  1. Beta-thalassemia (intermedia or major)
  2. Hemoglobin H (HbH) disease
  3. HbH with non-deletional mutations (e.g., HbH Constant Spring)
  4. E-beta-thalassemia
  5. Homozygous alpha-thalassemia (i.e., 4-gene alpha deletion or equivalent null alpha mutation)
  6. Other thalassemic conditions not explicitly excluded
  7. Thalassemia intermedia due to heterozygous beta mutation with alpha-gene excess
* Requires at least annual monitoring for end-organ injury related to thalassemia, including all clinical measures specified in this study

Inclusion Criteria for People who Have Received a Successful Stem Cell Transplant:

* Received a successful hematopoietic stem cell transplant, defined as engraftment of all three cell lines and transfusion independence by 100 days post-transplant, for any of the thalassemia disorders listed above
* Monitored for end-organ injury related to thalassemia before their successful stem cell transplant, including all clinical measures specified in this study

Exclusion Criteria for People with Thalassemia:

* Has any of the following mild or mixed diagnoses:

  1. Thalassemia trait (i.e., single recessive beta-gene mutation, two-gene alpha-gene mutation)
  2. Thalassemia/Hb S, C, or D compound heterozygotes
  3. HbH with steady state hemoglobin above 9.0 g/dL and no history of significant thalassemia complications (e.g., endocrinopathies, cardiac dysfunction, growth impairment, pulmonary hypertension)
* Unable or unwilling to be followed annually
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:

* Thalassemia major patients with serum ferritin concentration between 800 to 3,000 ng/ml and were over 13 years of age

Exclusion Criteria:

* Known intolerance to one of the trial treatments
* Platelet count \< 100,000/mm3 or or leukocyte count \< 3,000/mm3
* Severe liver damage indicated by ascites
* Heart failure
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: B