Deferasirox in Treating Patients With Iron Overload After Undergoing a Donor Stem Cell Transplant

Study Overview
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Brief Summary
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RATIONALE: Deferasirox may be effective in treating iron overload caused by blood transfusions in patients who have undergone donor stem cell transplant. PURPOSE: This phase II trial is studying the side effects and how well deferasirox works in treating patients with iron overload after donor stem cell transplant.

Detailed Description
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OBJECTIVES: Primary To evaluate the safety of deferasirox given over 6 months in reducing liver iron concentration in patients with transfusional iron overload after undergoing allogeneic hematopoietic stem cell transplantation. Secondary To evaluate the efficacy of deferasirox in reducing liver iron overload in these patients. OUTLINE: This is a multicenter study. Patients receive oral deferasirox once daily for 6 months in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed at 4 weeks.

Official Title
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Open-Label Single-Arm Pilot Study of Deferasirox (Exjade®) in Adult Allogeneic Hematopoietic Stem Cell Transplant Recipients With Transfusional Iron Overload

Conditions
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Breast Cancer, Iron Overload, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Neuroblastoma, Ovarian Cancer

Intervention / Treatment
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* Drug: deferasirox


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of iron overload, defined as serum ferritin > 1,000 ng/mL and liver iron concentration ≥ 5 mg iron/g on tissue proton transverse relaxation rates Magnetic Resonance Imaging (MRI) Underwent prior allogeneic hematopoietic stem cell transplantation (HSCT) using either myeloablative or reduced-intensity conditioning at least 12 months ago No evidence of relapse or progression of the primary disease for which allogeneic HSCT was performed Patients who have become red-cell transfusion independent (i.e., no red cell transfusions within the past 3 months) as well as patients who require red cell transfusions are eligible Meets one of the following criteria: Ineligible for phlebotomy (hemoglobin < 11 g/dL, poor intravenous access, or unable to undergo phlebotomy every 4 weeks) Have failed treatment with phlebotomy (serum ferritin > 50% of baseline after 3 months of phlebotomy) Refused phlebotomy ECOG performance status of 0-2 Life expectancy ≥ 6 months Adequate renal function defined as serum creatinine < or = 1.6 mg/dL and creatinine clearance of > or = 60 ml/min calculated using the Crockcroft-Gault formula on 2 occasions within 30 days of enrollment Sexually active men and women must use an effective method of contraception. Alternatively, women must have undergone clinically documented total hysterectomy and/or oophorectomy, or tubal ligation or be postmenopausal. Must be able to give written informed consent. Prior therapy with deferoxamine allowed provided it was completed ≥ 12 months ago Exclusion Criteria: Contraindication for performing MRI or inability to undergo MRI because of claustrophobia or weight (>350 pounds). Inability to take medications orally. Uncontrolled bacterial, viral, or fungal infection ANC ≥ 1,000/mm³ Hemoglobin ≥ 8.0 g/dL Platelet count ≥ 50,000/mm³ Aspartate aminotransferance (AST) and alanine aminotransferase (ALT) ≤ 5 times the upper limit of normal Less than 4 weeks since prior and no concurrent systemic investigational drug Less than 7 days since prior and no concurrent topical investigational drug. Concurrent non-investigational medications needed to treat concomitant medical conditions are allowed, with the exception of other chelating agents. Concurrent growth factors such as epoetin alfa, darbepoetin alfa, filgrastim (G-CSF), and sargramostim (GM-CSF) allowed. Concurrent irradiated packed red-cell and platelet transfusions allowed as clinically indicated. Concurrent low-doses of vitamin C supplements (≤ 200 mg/day) allowed. Concurrent iron supplements or multivitamins with iron. Aluminum-containing antacid therapies may not be taken simultaneously with deferasirox, but may be taken 2 hours before or after administration of deferasirox On dialysis or status post-renal transplantation Pregnant or nursing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Deferasirox Treated<br>Includes patients that were treated with deferasirox for 6 months. | Drug: deferasirox<br>* 20 mg/kg once daily orally for 6 months<br>* Other names: Exjade;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Not Completing Treatment | Number of patients who discontinued deferasirox during 6 month daily treatment due to drug related toxicity | 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in Liver Iron Concentration After Study Drug | Efficacy as measured by reduction in liver iron concentration (LIC) after 6 months of the study drug compared to baseline (LIC at baseline minus LIC at 6 months). This shows the mean reduction for the 3 subjects treated in this study. | 6 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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iron overload