Please select the eligibility criteria that correspond to the clinical trial below.
Title: An Extension Study of Iron Chelation Therapy With Deferasirox (ICL670)in β-thalassemia Patients With Transfusional Iron Overload
Brief Summary: A 1-year randomized Phase III core trial (NCT00061750) using deferoxamine as the comparator was conducted to investigate the efficacy of deferasirox in regularly transfused patients with β-thalassemia 2 years of age and older. Patients who successfully completed this main trial may continue in this extension trial to receive chelation therapy with deferasirox for an additional 4 years.

The objective of this study is to assess the efficacy and long-term safety of deferasirox in regularly transfused patients with β-thalassemia 2 years of age and older.


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: Inclusion Criteria:

* Patients presenting with transfusion-dependent anemias (independent of underlying condition) with transfusional iron overload as shown by a serum ferritin level of ≥ 1000 ng/ml
* Patients of either gender and aged ≥ 2 years
* Female patients who have reached menarche and who are sexually active must use an effective method of contraception, or must have undergone clinically documented total hysterectomy and/or ovariectomy, or tubal ligation.

Additional Inclusion Criteria for Adult Patients:

* Written informed consent by the patient

Additional Inclusion Criteria for Pediatric Patients:

* The definition of the term "pediatric" will be in accordance with local legislation. Parents or legal guardians will be fully informed by the investigator as to the requirements of the study. The pediatric patients themselves will be informed according to their capabilities in a language and terms that they are able to understand. Written informed consent will be obtained from their parents or legal guardians on the patient's behalf in accordance with the national legislation. If capable, all patients should also personally sign their written informed assent.

Exclusion Criteria:

* Non-transfusional hemosiderosis
* Patients with clinical evidence supporting the need for intensive chelation, based on the investigator's judgment
* Patients with mean levels of alanine aminotransferase (ALT) \> 300 U/l
* Patients with uncontrolled systemic hypertension
* Patients with serum creatinine above the upper limit of normal (ULN)
* Significant proteinuria as indicated by a urinary protein/creatinine ratio \> 0.5 (mg/mg) in second-voiding urine samples taken at both visits 1 and 2. A third sample is to be taken from patients in whom one ratio is \> 0.5 (mg/mg) and one is ≤ 0.5 (mg/mg) and patients in whom the urinary protein/creatinine ratio is \> 0.5 (mg/mg) in two of the three determinations are also to be excluded.
* History of nephrotic syndrome
* Patients with 3rd atrioventricular (A-V) block, clinically relevant Q-T interval prolongation as well as patients requiring treatment with digoxin and similar compounds or drugs which may induce prolongation of the Q-T interval
* Patients with a previous history of clinically relevant ocular toxicity related to iron chelation
* Systemic diseases (cardiovascular, renal, hepatic, etc.) which would prevent the patient from undergoing study treatment
* Patients with psychiatric or addictive disorders which prevent them from giving their informed consent or undergoing study treatment
* Pregnant or breast feeding patients
* Patients treated with systemic investigational drugs within the past 4 weeks or topical investigational drugs within the past 7 days
* Any other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug. The investigator should be guided by evidence of any of the following:

  * history of inflammatory bowel syndrome, gastritis, ulcers, gastrointestinal or rectal bleeding;
  * history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
  * history of pancreatic injury or pancreatitis; indications of impaired pancreatic function/injury as indicated by abnormal lipase or amylase;
  * history or presence of impaired renal function as indicated by creatinine or blood urea nitrogen (BUN) values equal or above ULN;
  * history of urinary obstruction or difficulty in voiding.
* History of non-compliance to medical regimens and patients who are considered potentially unreliable and/or not cooperative
* History of drug or alcohol abuse within the 12 months prior to dosing or evidence of such abuse as indicated by the laboratory assays conducted during the run-in period
* Patients with positive test to HIV
* Life expectancy of \< 1 year

Exclusion Criteria for Pediatric Patients:

* Patient body weight which prevents the use of the smallest tablet strength (i.e. 125 mg) for proper dosing

Other protocol-defined inclusion/exclusion criteria may apply.
C: 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
D: Inclusion Criteria:

* Subjects with transfusional iron overload secondary to thalassemia major, aged 18 or older, may participate after giving written informed consent. Subjects must have no clinically significant finding in their medical history, on physical examination or as a result of laboratory assessments other than those consistent with thalassemia major and its complications, such as compensated cirrhosis, endocrine insufficiency and diabetes.
* Subjects must have a serum ferritin greater than 1000 ng/mL, a platelet count greater than 100,000/mm3, and a serum creatinine within the normal range.
* Subjects must be willing and able to discontinue their usual regimen of DFO, deferiprone (L1, Ferriprox) or Exjade for the duration of the study.
* 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. Acceptable birth control measures include: abstinence, oral contraceptives, hormonal contraceptive implants, barrier contraceptives (condom, diaphragm with spermicide), IUD, and/or a vasectomized partner. Male subjects must also use barrier contraceptives during the study and for 1 month thereafter.
* 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.
* Subjects must weigh at least 40 kg.

Exclusion Criteria:

* Subjects can not have a history of clinically significant gastrointestinal, renal, hepatic, endocrine, oncologic, infectious, pulmonary or cardiovascular disease, other than conditions associated with thalassemia and iron overload, such as compensated cirrhosis, endocrine insufficiency and diabetes, or 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 can not be 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. A chelation regimen including deferiprone or Exjade within 30 days of screening would not exclude subjects coming from regions where these drugs are an approved medication.
* 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 with abnormal or irregular bowel function (defined as more than 3 bowel movements/day or less than 1 bowel movement every other day).
* Subjects receiving warfarin, digoxin, or anti-arrhythmic or anti-seizure medications.
* Subjects with a known allergy to Exjade or DFO that prevents chronic administration.

Answer: A