Deferoxamine for Iron Overload Before Allogeneic Stem Cell Transplantation

• Sponsor: Dana-Farber Cancer Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00658411
• Collaborator: Brigham and Women's Hospital (Other)
• Enrollment: 5
• Locations: 2
• Arm: 1
• Duration (Months): 40
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndrome	Drug: deferoxamine	N/A

Detailed Description

See above

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Pilot Study of Deferoxamine Before and During Myeloablative Allogeneic Stem Cell Transplantation for Patients With Myelodysplastic Syndromes or Acute Leukemia and Iron Overload
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: All patients Deferoxamine for >=2 weeks prior to stem cells	Drug: deferoxamine; 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.; Other Names: Desferal deferoxamine mesylate

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
2	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Dana-Farber Cancer Institute
• Brigham and Women's Hospital

Investigators

• Principal Investigator: Philippe Armand, MD, PhD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Philippe Armand, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT00658411
• Other Study ID Numbers: 07-411
• First Posted: Apr 15, 2008
• Last Update Posted: Apr 9, 2013
• Last Verified: Apr 1, 2013

• Keywords provided by Philippe Armand, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute: AML; ALL; MDS; iron overload; deferoxamine
• Additional relevant MeSH terms: Leukemia; Preleukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Iron Overload; Deferoxamine

Study Results

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.

Arm/Group Title	All Patients
Arm/Group Description	Deferoxamine for >= 2 weeks prior to stem cells
Period Title: Overall Study
STARTED	5
COMPLETED	5
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Patients
Arm/Group Description	Deferoxamine prior to stem cells
Overall Participants	5
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	5 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48 (9.8)
Sex: Female, Male (Count of Participants)
Female	2 40%
Male	3 60%
Region of Enrollment (participants) [Number]
United States	5 100%

Outcome Measures

1. Primary Outcome

Title	Safety of Deferoxamine Therapy Determined by the Number of Participants With Grade 3 or Higher Toxicities.
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Deferoxamine
Arm/Group Description	All patients received a maximum dose of 50mg/kg/d of deferoxamine as chelation therapy for at least 2 weeks prior to receiving myeloablative transplant.
Measure Participants	5
Baseline	5 (9.8) 100%
6 month	0 0%
1 year	0 0%

2. Secondary Outcome

Title	1-year Post-Transplant Survival
Description	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

Outcome Measure Data

Analysis Population Description

Stopped early for poor accrual

Arm/Group Title	Transplant-Related Mortality (Deferoxamine)	Relapse (Deferoxamine)	Disease-Free Survival (Deferoxamine)	Overall Survival (Deferoxamine)
Arm/Group Description	Patients who received Deferoxamine and passed away as a result of transplant or study treatment without prior relapse at 1 year.	Patients who received Deferoxamine and relapsed post transplant at 1 year.	Patients who received Deferoxamine and are currently alive without incidence of relapse at 1 year.	Patients who received Deferoxamine and have relapsed and is alive at 1 year.
Measure Participants	5	5	5	5
Number [participants]	0 0%	0 NaN	5 NaN	0 NaN

Adverse Events

Time Frame	All patients were monitored for toxicities from the time of chelation to study completion (1 year post transplant).
Arm/Group Title	Deferoxamine
Arm/Group Description	All patients received a maximum dose of 50mg/kg/d of deferoxamine as chelation therapy for at least 2 weeks prior to receiving myeloablative transplant.
All Cause Mortality
	Deferoxamine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Deferoxamine
	Affected / at Risk (%)	# Events
Total	1/5 (20%)
Vascular disorders
Hypotension	1/5 (20%)	5
Other (Not Including Serious) Adverse Events
	Deferoxamine
	Affected / at Risk (%)	# Events
Total	0/5 (0%)

Limitations/Caveats

The number of patients enrolled on this study is far too small to draw reliable conclusions.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.