Breast Cancer, Iron Overload, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Neuroblastoma, Ovarian Cancer
Conditions
Keywords
iron overload
Brief summary
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
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.
Interventions
DRUGdeferasirox
20 mg/kg once daily orally for 6 months
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Not Completing Treatment | 6 Months | Number of patients who discontinued deferasirox during 6 month daily treatment due to drug related toxicity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reduction in Liver Iron Concentration After Study Drug | 6 Months | 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. |
Countries
United States
Participant flow
Recruitment details
Only one site (Masonic Cancer Center) enrolled patients in this study.
Pre-assignment details
4 patients were consented, however, one withdrew consent before receiving treatment.
Participants by arm
| Arm | Count |
|---|---|
| Deferasirox Treated Includes patients that were treated with deferasirox for 6 months. | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | Deferasirox Treated |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Age, Continuous | 45.7 years STANDARD_DEVIATION 5 |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Number of Patients Not Completing Treatment
Number of patients who discontinued deferasirox during 6 month daily treatment due to drug related toxicity
Time frame: 6 Months
Population: Note: 1 patient had a transient decrease in hemoglobin that required discontinuation of treatment for 2 weeks; subsequently restarted at same dose and completed therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Deferasirox Treated | Number of Patients Not Completing Treatment | 0 Participants |
Secondary
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.
Time frame: 6 Months
Population: All patients included in count.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deferasirox Treated | Reduction in Liver Iron Concentration After Study Drug | 5.6 milligrams/gram | Standard Deviation 4.8 |