Iron Balance Study of Deferasirox, Deferoxamine and the Combination of Both

• Status: Unknown status
• Trial end date: 2009-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Subjects with thalassemia major require regular transfusion therapy to sustain life. The iron present in the transfused blood remains in the body where it can cause a variety of organ dysfunctions. Lifelong iron chelation therapy is needed to maintain iron balance but its effectiveness varies greatly. Like that of deferoxamine (Desferal, DFO) the mainstay of chelation therapy for 30 years, the effectiveness of deferasirox (Exjade, ICL670), the newly approved, orally effective iron chelating drug, is not satisfactory in all subjects. Even with good compliance, the iron excretion induced by a given drug exhibits wide subject-to-subject variability. There is often persistent iron overload of extra hepatic tissues such as the heart and pancreas leading to cardiac disease and diabetes. Combining the drugs may be a better approach in those subjects at increased risk. The iron balance studies proposed will permit an assessment of the potential of such a combination to place subjects in net negative iron balance and the relative effectiveness of the combination in relation to that of the individual drugs, an additive effect being expected. With such information, physicians will be able to design individualized chelation regimens that maximize effectiveness while minimizing side effects by adjusting the ratio and/or the dosing schedule of the two drugs.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Weill Medical College of Cornell University
• Treatments: Deferasirox; Deferoxamine; Iron

Criteria

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.