Deferasirox for Treating Patients Who Have Undergone Allogeneic Stem Cell Transplant and Have Iron Overload

Deferasirox Treatment and Labile Plasma Iron in Iron Overloaded Patients Who Have Undergone Allogeneic Hematopoietic Stem Cell Transplantation

RATIONALE: Low dose deferasirox may be safe and effective in treating patients who have undergone hematopoietic stem cell transplant and have iron overload.

PURPOSE: This pilot clinical trial studies safety and tolerability of deferasirox in hematopoietic stem cell transplant recipients who have iron overload. Effect of low dose deferasirox on labile plasma iron is also examined.

PRIMARY OBJECTIVES:

I. To determine labile plasma iron (LPI) levels in iron overloaded patients after allogeneic Hematopoietic Stem Cell Transplantation (HSCT).

II. To determine safety and tolerability of low dose deferasirox in the post allogeneic HSCT setting.

SECONDARY OBJECTIVES:

I. To determine ability of deferasirox to suppress LPI in allogeneic HSCT patients with serum ferritin over 1500 ng/ml.

II. To determine prevalence of elevated LPI in allogeneic HSCT recipients with serum ferritin over 1500 ng/ml.

III. To determine ability of low dose deferasirox to lower serum ferritin during the treatment period.

IV. To correlate LPI with serum ferritin in allogeneic HSCT recipients with serum ferritin over 1500 ng/ml.

OUTLINE: Patients receive deferasirox at 10 mg/kg once daily for 6 months in the absence of unacceptable toxicity. Labile plasma iron will be measured at baseline and at weeks 4, 12, and 24. Side effects of deferasirox will be recorded.

Inclusion

• Patients must have undergone a matched related donor, matched unrelated donor or cord blood Hematopoietic Stem Cell Transplant (HSCT) over 6 months ago
• Patients currently on Desferal (desferrioxamine) therapy will require a one day wash out prior to the first dose of study drug
• Serum ferritin >= 1500 ng/mL on two occasions two weeks apart at screening; samples must be obtained in the absence of concomitant infection
• Normal C-reactive protein level at screening
• Patients must be red cell transfusion independent for 2 months prior to enrollment
• Sexually active women must use an effective method of contraception, or must have undergone clinical documented total hysterectomy and/or oophorectomy, or tubal ligation or be postmenopausal (defined as amenorrhea for at least 12 months)
• Written informed consent by the patient

Exclusion

• Chronic hepatic GVHD with serum total bilirubin over 2 mg/dL
• Known hypersensitivity to deferasirox
• Serum creatinine above the upper limit of normal
• AST or ALT > 200 U/L during screening
• Clinical or laboratory evidence of active Hepatitis B or Hepatitis C (HBsAg in the absence of HBsAb OR HCV Ab positive with HCV RNA positive and ALT above the normal range)
• History of HIV positive test result (ELISA or Western blot)
• History of drug or alcohol abuse within the 12 months prior to enrollment
• ECOG Performance Status > 2
• Patients with a diagnosis of or history of clinically relevant ocular toxicity related to iron chelation
• Systemic diseases (cardiovascular, renal, hepatic, etc.) which would prevent study treatment
• Pregnancy (as documented in required screening laboratory test) or breast feeding
• 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
• Other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of study drug
• History of non-compliance to medical regimens or patients who are considered potentially unreliable and/or not cooperative