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

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.

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