Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Myelodysplastic Syndrome
Conditions
Keywords
AML, ALL, MDS, iron overload, deferoxamine
Brief summary
The objective of this research study is to determine the safety and feasibility of chelation therapy with deferoxamine for patients with iron overload who are receiving a stem cell transplant. Patients who have iron overload prior to stem cell transplantation may have more toxicity from the transplantation procedure, and thus may benefit from an attempt at iron chelation pre- and peri-transplantation. In this study we are examining the use of deferoxamine starting 2 weeks to 3 months prior to transplantation and continuing through the preparative regimen.
Detailed description
See above
Interventions
DRUGdeferoxamine
Given intravenously or subcutaneously over 8-12 hours daily for at least three weeks prior to transplantation date and continue until the day before the participant receives their donor's stem cells.
Sponsors
Brigham and Women's Hospital
Dana-Farber Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age or older * Histologically confirmed acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome * Planned allogeneic stem cell transplantation with myeloablative conditioning regimen; the planned date of transplantation must be at least 4 weeks from time of enrollment * Severe iron overload as defined by BOTH: Ferritin greater than 1000ng/ml (at the time of donor availability) and Liver iron content estimated greater than or equal to 5mg/g dry weight by MRI (at the time of donor availability) * Patients with a history of prior autologous transplantation will be eligible for this study
Exclusion criteria
* Contraindication to magnetic resonance imaging (MRI) * Creatinine \>2.0mg/dl or creatinine clearance \<50ml/min * Active uncontrolled bacterial or fungal infection * History of mucormycosis * Pre-existing clinically apparent retinal neuropathy. If patients have clinically apparent visual loss at the time of screening, they will be excluded if either they have known retinal neuropathy or if this cannot be excluded by further testing * Pre-existing clinically apparent sensorineural hearing loss. If patients have auditory loss at the time of screening, they will be excluded if either they have known sensorineural hearing loss, or if this cannot be excluded by further testing * Pregnancy or inability or unwillingness to use contraception during the time of the study * Lactating patients * Inability to provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of Deferoxamine Therapy Determined by the Number of Participants With Grade 3 or Higher Toxicities. | Baseline , 6 month, 1 year | All patients meeting the criteria for Severe iron overload as defined by BOTH: ferritin ≥ 1000 ng/ml and liver iron content(LIC) ≥ 5 mg/gdw were enrolled and received chelation therapy with Deferoxamine. All patients who received chelation therapy were monitored for grade 3 or above toxicity Attributable to Deferoxamine(grades defined by the CTCAE Version 3). The number of participants with grade 3 or higher toxicities were measured and used to determine the safety of chelation therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 1-year Post-Transplant Survival | 1 year | Survival information for the 5 patients who were treated with deferoxamine was collected. This information was used to determine transplant-related mortality, relapse, disease-free and overall survival. |
Countries
United States
Participant flow
Recruitment details
Adult patients with AML, ALL, MDS scheduled for HSCT with myeloablative conditioning, who in addition were found to have both a serum ferritin ≥ 1000 ng/ml and a liver iron content (LIC) \> 5 mg/g dry weight (mg/gdw) based on hepatic T2\* measurement, were offered enrollment on the chelation study.
Participants by arm
| Arm | Count |
|---|---|
| All Patients Deferoxamine prior to stem cells | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | All Patients |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age Continuous | 48 years STANDARD_DEVIATION 9.8 |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 2 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 | 0 / 5 |
| serious Total, serious adverse events | 1 / 5 |
Outcome results
Primary
Safety of Deferoxamine Therapy Determined by the Number of Participants With Grade 3 or Higher Toxicities.
All patients meeting the criteria for Severe iron overload as defined by BOTH: ferritin ≥ 1000 ng/ml and liver iron content(LIC) ≥ 5 mg/gdw were enrolled and received chelation therapy with Deferoxamine. All patients who received chelation therapy were monitored for grade 3 or above toxicity Attributable to Deferoxamine(grades defined by the CTCAE Version 3). The number of participants with grade 3 or higher toxicities were measured and used to determine the safety of chelation therapy.
Time frame: Baseline , 6 month, 1 year
Population: Patients who met criteria for iron overload pre-transplant, as defined by the protocol, were enrolled on study for chelation therapy. Those patients who received therapy were monitored for toxicities using the CTCAE version 3.0.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Deferoxamine | Safety of Deferoxamine Therapy Determined by the Number of Participants With Grade 3 or Higher Toxicities. | Baseline | 5 Participants | 9.8 |
| Deferoxamine | Safety of Deferoxamine Therapy Determined by the Number of Participants With Grade 3 or Higher Toxicities. | 6 month | 0 Participants | — |
| Deferoxamine | Safety of Deferoxamine Therapy Determined by the Number of Participants With Grade 3 or Higher Toxicities. | 1 year | 0 Participants | — |
Secondary
1-year Post-Transplant Survival
Survival information for the 5 patients who were treated with deferoxamine was collected. This information was used to determine transplant-related mortality, relapse, disease-free and overall survival.
Time frame: 1 year
Population: Stopped early for poor accrual
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Deferoxamine | 1-year Post-Transplant Survival | 0 participants |
| Relapse (Deferoxamine) | 1-year Post-Transplant Survival | 0 participants |
| Disease-Free Survival (Deferoxamine) | 1-year Post-Transplant Survival | 5 participants |
| Overall Survival (Deferoxamine) | 1-year Post-Transplant Survival | 0 participants |