Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-blind, Placebo-controlled, Phase II Study to Evaluate Efficacy and Safety of Deferasirox in Non-transfusion-dependent Thalassemia Patients With Iron Overload
Brief Summary: CICL670A2209: This study will evaluate the safety and efficacy of deferasirox in non-transfusion dependent thalassemia patients with iron overload. Patients will be treated either with active treatment (deferasirox) or placebo for 12 months (core study phase). Patients who complete the core study phase will be offered to continue their study with the active treatment (deferasirox) in a 12 months extension phase. During the core and extension, the effects of treatment on iron overload in the liver will be evaluated using magnetic resonance imaging (MRI) assessments.

CICL670A2209E1: A one-year open-label extension to a randomized, double-blind, placebo-controlled, phase II study to evaluate efficacy and safety of deferasirox in non-transfusion dependent thalassemia patients with iron overload (Thalassa).


Options:
A: 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
B: Core Inclusion Criteria:

* Male or female aged ≥ 10 years with non-transfusion dependent syndromes, not requiring transfusion within 6 months prior to study start. Note: there was a local country amendment for Greece only to change the age specific inclusion criteria to ≥ 18 years old
* Liver iron concentration ≥ 5 mg/g dry weight measured by Magnetic resonance imaging (MRI) before study start
* Serum ferritin \>300 ng/mL at screening

Core Exclusion Criteria:

* Hemoglobin S (HbS)-variants of thalassemia syndromes
* Anticipated regular transfusion program during the study. Patients having a sporadic transfusion (e.g. in case of infection) throughout the study course will not be excluded
* Any blood transfusion 6 months prior to study start
* Creatinine clearance ≤ 60 mL/min at screening
* Serum creatinine above the upper limit of normal at both screening visits
* Significant proteinuria as indicated by a urine protein/urine creatinine ratio \> 1.0 mg/mg
* Alanine aminotransferase (ALT) of \> 5 x the upper limit of normal at both screening visits
* Concomitant therapy with hydroxyurea, erythropoietin, butyrate
* History of deferasirox treatment
* Pediatric patients: a patient's weight of below 20 kg

Extension Inclusion Criteria:

* Patients who completed the core CICL670A2209 clinical trial
* Written informed consent obtained prior entry to one year extension study CICL670A2209

Extension Exclusion Criteria:

* Patients with a continuous increase in serum creatinine ≥ 33% above the baseline value and \> ULN who did not improve after drug interruption or dose reduction in the core study
* Patients with a continuous increase in ALT greater than 2 times the baseline value and \> 5 times ULN who did not improve after drug interruption or dose reduction in the core study
* Patients with progressive proteinuria, as assessed by the investigator, who did not improve after drug interruption or dose reduction in the core study
* Significant medical condition interfering with the ability to partake in this study (e.g.systemic uncontrolled hypertension, unstable cardiac disease not controlled by standard medical therapy, systemic disease (cardiovascular, renal, hepatic, etc.)

Other protocol-defined inclusion/exclusion criteria may apply
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: 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

Answer: B