Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 2, 24 Week, Randomized, Open Label, Multi-Center Study to Assess the Safety, Tolerability, and Pharmacodynamics of FBS0701 in the Treatment of Chronic Iron Overload Requiring Chelation Therapy, With a 72 Week Dosing Extension
Brief Summary: The purpose of this research study is to evaluate the safety of two doses of FBS0701, a new oral iron chelator, and its effectiveness in clearing iron from the liver. FBS0701 is a medication taken by mouth that causes the body to get rid of iron. Iron chelators are used in patients with β-thalassemia and other forms of anemia who experience iron overload - iron increases in the body as a result of regularly required blood transfusions. Patients who qualify will be randomized to receive one of two doses of FBS0701 for up to 24 weeks (6 months) with a total study duration of up to 33 weeks. These patients will be eligible to participate in a dosing extension for up to 72 weeks. The maximum duration of dosing will be up to 96 weeks. The safety of patients will be monitored frequently during the study by physical exams, ECGs, and blood tests. To assess the amount of iron in the liver and heart, each patient must undergo 6 MRI scans during the study. Patients will not need to stay in the hospital for this study but will need to visit the outpatient clinic up to 28 times over the 96 week period. Patients currently taking an iron chelator will be required to stop for a total of up to 26 weeks. The results of this study will help to determine if FBS0701 may be effective as an iron chelator.


Options:
A: Inclusion Criteria:

1. Patients with thalassemia major with at least 6 years of age undergoing iron chelation therapy.
2. No anticipated changes in chelation regimen for the next 12 months
3. Completed and signed Informed Consent

Exclusion Criteria:

1. Pregnancy
2. Advanced class III/IV heart failure or LVEF \< 0.35% (by MRI)
3. Formal contra-indications to MRI (pacemakers, cerebral aneurysm metal clips, etc).
4. Advanced heart AV block
B: Part I: Inclusion criteria for Inadequate responders

* Male or female patients with transfusion dependent iron overload including patients with thalassemia syndromes, sickle cell disease and bone marrow failure.
* Patients currently on Desferal (desferrioxamine) therapy will require a one day wash out prior to the first dose of study drug.
* Dose of deferasirox: \>30 mg/kg/day of deferasirox for at least 3 months
* No improvement or worsening of liver iron content (LIC) if this has been evaluated on deferasirox in the 3 months preceding the baseline studies.
* Age greater than 6 years
* Serum Ferritin: Ferritin \>1500 ng/ml and rising over three month period while on deferasirox.
* Patients had to achieve 'failure' as described above previously and may or may not currently be on deferasirox and may currently be having adequate responses on doses greater than or equal to 35 mg/kg/day of deferasirox.
* Life expectancy ≥ 6 months
* Written informed consent by the patient or for pediatric patients consent of the patient's legal guardian. The definition of the term 'pediatric' for enrollment and study conduct will be in accordance with Children's Hospital IRB. Parents or the legal guardians will be fully informed by the investigator as to the requirements of the study. Pediatric patients themselves will be informed according to their capabilities in a language and in terms that they are able to understand. Written informed consent will be obtained from their legal guardian on the patient's behalf in accordance with national legislation. If capable, all patients should also personally sign their written informed consent.

Part I: Inclusion criteria for good responders:

* Male or female patients with transfusion dependent iron overload including patients with thalassemia syndromes, sickle cell disease and bone marrow failure.
* Patients currently on Desferal (desferrioxamine) therapy will require a one day wash out prior to the first dose of study drug.
* Serum ferritin less than or equal to 1000 ng/ml or declining over a 3 month period on a dose of less than 30 mg/kg of deferasirox.
* Age greater than 6 years
* Life expectancy ≥ 6 months
* Written informed consent by the patient or for pediatric patients consent of the patient's legal guardian. The definition of the term 'pediatric' for enrollment and study conduct will be in accordance with Children's Hospital IRB. Parents or the legal guardians will be fully informed by the investigator as to the requirements of the study. Pediatric patients themselves will be informed according to their capabilities in a language and in terms that they are able to understand. Written informed consent will be obtained from their legal guardian on the patient's behalf in accordance with national legislation. If capable, all patients should also personally sign their written informed consent.

Exclusion criteria for Part I:

* Pregnancy (as documented in required screening laboratory test) or breast feeding
* History of non-compliance to medical regimens or patients who are considered potentially unreliable and/or not cooperative
* Patients with transfusion requirements equal to or more frequent than every three weeks.
* AST or ALT \> 400 U/L during screening
* Patients with uncontrolled systemic hypertension
* Severe cardiac insufficiency (NYHA III or IV), with uncontrolled and/or unstable cardiac or coronary artery disease not controlled by standard medical therapy
* Patients who received treatment with systemic investigational drug within the past 4 weeks or topical investigational drug within the past 7 days or are planning to receive other investigational drugs while participating in the study
* Allergy to deferoxamine
* Known contraindication to having a nuclear medicine study
* Any other condition which in the opinion of the investigator would prevent completion of the trial.
* Prior possible toxicity is not an exclusion criteria for Part I because patients require a chelating agent of which there are only two Patients who are found to be ineligible after screening procedures will have this documented on the screening log. No further data will be collected in the CRF for these patients.

Exclusion criteria for Part II:

* Patients with unacceptable toxicity to deferasirox such as renal failure or worsening cardiac function
* Patients who have failed to achieve negative iron balance at the maximum tolerated dose of deferasirox
* Patients who require an alternative chelator for specific reasons
* Patients who are currently enrolled on conflicting therapeutic trials
* Patients with serum ferritin less than 500 ng/ml at screening
* Any other condition which in the opinion of the investigator would prevent completion of the trial
C: Inclusion Criteria:

* Transfusional iron overload due to: hereditary anemias such as sickle cell disease, β-thalassemia and Diamond-Blackfan anemia; acquired anemias such as Myelodysplastic Syndrome and other forms of bone marrow failure. Patients must also be transfusion-dependent and require chronic treatment with deferoxamine, deferasirox, and/or deferiprone.
* Willing to discontinue all existing iron chelation therapies throughout study period.
* Serum ferritin greater than 500 ng/mL at Screening.
* Baseline liver iron concentration and cardiac MRI T2\* per protocol requirements.
* Mean of the previous three pre-transfusion hemoglobin concentrations greater than or equal to 7.5 g/dL.
* Agrees to use an approved method of contraception throughout study period.

Exclusion Criteria:

* As a result of medical review, physical examination or Screening investigations, the Principal Investigator considers the patient unfit for the study.
* Non-elective hospitalization within the 30 days prior to Baseline testing. (Patients with sickle cell anemia who are admitted to the hospital for management of sickle crisis pain whose uncomplicated hospital course was four days or less and who, 14 days prior to Baseline testing, have returned to their previous health status are acceptable.)
* Evidence of clinically relevant oral, cardiovascular, gastrointestinal, hepatic, renal, endocrine, pulmonary, neurologic, psychiatric, immunologic, bone marrow or skin disorder as determined by the Investigator.
* Evidence of significant renal insufficiency; possible examples include: serum creatinine above the upper limit of normal, proteinuria greater than 2 gm per day or calculated creatinine clearance of less than 60 mL/minute.
* Cardiac left ventricular ejection fraction outside of protocol requirements.
* Known sensitivity to magnesium stearate, croscarmellose sodium or FBS0701.
* Platelet count below 100,000/µL and/or absolute neutrophil count less than 1500/mm3 at Screening and \<50% at Baseline testing by MRI
* Alkaline phosphatase, AST or ALT outside of protocol requirements.
* Liver Function Tests: ALT \>5 times the local upper limit of normal on two occasions in the previous 12 months or ALT at Screening \>200 IU/L
* Use of any investigational agent within the 30 days prior to the Baseline testing.
D: Inclusion Criteria:

* Thalassaemia Major
* Patient must have had a cardiac MRI scan between 1999 and 2006

Exclusion Criteria:

* Other structural heart disease such as valvular abnormalities, MI, congenital heart disease

Answer: C