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

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

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.

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