Combined Chelation Therapy in Patients With Transfusion Dependent Thalassemia and Iron Overload

• Sponsor: Elliott Vichinsky (Other)
• Overall Status: Completed
• CT.gov ID: NCT00901199
• Collaborator: (none)
• Enrollment: 22
• Location: 1
• Arm: 1
• Duration (Months): 61
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This is a pilot study looking at the safety and efficacy of giving combination chelation with deferasirox and deferoxamine. The hypothesis is that combination chelation is safe in decreasing overall iron in patients with thalassemia.

Condition or Disease	Intervention/Treatment	Phase
Thalassemia; Iron Overload	Drug: Combo Chelation with Deferasirox (Exjade) and Deferoxamine (DFO)	Phase 2

Detailed Description

This was a phase two pilot clinical trial designed to evaluate the safety and efficacy of the combination of deferasirox and deferoxamine in transfusion dependent thalassemia with a range of systemic iron burden. The duration of combined therapy was 12 months. Changes in liver iron concentration, ferritin, myocardial iron, and serum creatinine was monitored.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety of Deferasirox (ICL670) and Deferoxamine (Desferal or DFO) Combined Chelation Therapy in Patients With Transfusion Dependent Thalassemia and Iron Overload
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Oct 1, 2012
• Actual Study Completion Date: Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Deferasirox (Exjade) and Deferoxamine (DFO) All subjects received Deferasirox (Exjade) and Deferoxamine (DFO) dosing based on the iron overload at baseline.	Drug: Combo Chelation with Deferasirox (Exjade) and Deferoxamine (DFO); All subjects will be given Deferasirox 20-30 mg/kg for 7 days per week. All subject will be given Deferoxamine 50 mg/kg for 3-7 days per week. The number of days for Deferoxamine will be determined by liver iron concentration at baseline.; Other Names: Deferasirox, (Exjade) Deferoxamine (DFO)

Outcome Measures

Primary Outcome Measures

1. Efficacy of Combined Treatment With Deferasirox and Deferoxamine Over 12 Months [12 months]

   Change in liver iron concentration from baseline to 12 months with the use of combined chelation therapy. The change was calculated as the liver iron concentration at 12 months minus the value at baseline.

2. Change in Serum Creatinine During 12 Months Combined Chelation Therapy [12 months]

   Comparison of average serum creatinine over 12 months of combined chelation therapy compared with baseline serum creatinine.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Transfusion Dependent Thalassemia

• If iron between 5-15 mg/g dry liver by SQUID, subject must have a documented endocrinopathy or cardiac finding

• Older than 8 years

Exclusion Criteria:

• Participating on another interventional clinical trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CHRCO	Oakland	California	United States	94609

Sponsors and Collaborators

• Elliott Vichinsky

Investigators

• Principal Investigator: Elliot Vichinsky, MD, UCSF Benioff Children's Hospital Oakland

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Elliott Vichinsky, Director, Hematology/Oncology, UCSF Benioff Children's Hospital Oakland
• ClinicalTrials.gov Identifier: NCT00901199
• Other Study ID Numbers: CICL670AUS24T
• First Posted: May 13, 2009
• Last Update Posted: Aug 12, 2021
• Last Verified: Jul 1, 2021

• Keywords provided by Elliott Vichinsky, Director, Hematology/Oncology, UCSF Benioff Children's Hospital Oakland: Thalassemia; Chelation; Iron Overload; Thalassemia patients with Iron overload
• Additional relevant MeSH terms: Thalassemia; Iron Overload; Deferasirox; Deferoxamine

Study Results

Participant Flow

Arm/Group Title	Deferasirox (Exjade) and Deferoxamine (DFO)
Arm/Group Description	Patients will receive combined chelation therapy using Deferasirox (Exjade) and Deferoxamine (DFO) with dosing based on liver iron concentration at baseline. Patients with moderate iron overload,defined as liver iron concentration of 5-15mg/g plus a documented endocrinopathy or cardiac iron (low MRI T2*), will receive 7 days per week of Deferasirox (Exjade) 20-30 mg/kg and Deferoxamine (DFO) 50 mg/kg 3-5 days per week. Patients with high iron overload, defined as liver iron concentration over 15mg/g will receive Deferasirox (Exjade) 20-30 mg/kg 7 days per week and Deferoxamine (DFO) 50 mg/kg 5-7 days per week.
Period Title: Overall Study
STARTED	22
COMPLETED	18
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Deferasirox (Exjade) and Deferoxamine (DFO)
Arm/Group Description	Patients will receive combined chelation therapy using Deferasirox (Exjade) and Deferoxamine (DFO) with dosing based on liver iron concentration at baseline. Patients with moderate iron overload,defined as liver iron concentration of 5-15mg/g plus a documented endocrinopathy or cardiac iron (low MRI T2*), will receive 7 days per week of Deferasirox (Exjade) 20-30 mg/kg and Deferoxamine (DFO) 50 mg/kg 3-5 days per week. Patients with high iron overload, defined as liver iron concentration over 15mg/g will receive Deferasirox (Exjade) 20-30 mg/kg 7 days per week and Deferoxamine (DFO) 50 mg/kg 5-7 days per week.
Overall Participants	22
Age (Count of Participants)
<=18 years	6 27.3%
Between 18 and 65 years	16 72.7%
>=65 years	0 0%
Sex/Gender, Customized (Count of Participants)
Sex/Gender Not Collected	22 100%

Outcome Measures

1. Primary Outcome

Title	Efficacy of Combined Treatment With Deferasirox and Deferoxamine Over 12 Months
Description	Change in liver iron concentration from baseline to 12 months with the use of combined chelation therapy. The change was calculated as the liver iron concentration at 12 months minus the value at baseline.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Eighteen subjects completed one year of therapy. Four subjects did not complete the study for the following reasons: lost to follow-up (1), abdominal pain (1), death (1), and non-compliance (1).

Arm/Group Title	Deferasirox (Exjade) and Desferal (DFO)
Arm/Group Description	Subjects were treated with Deferasirox (Exjade) and Desferal (DFO) with dosing based on baseline iron overload.
Measure Participants	18
Median (Full Range) [mg/g]	-6.2

2. Primary Outcome

Title	Change in Serum Creatinine During 12 Months Combined Chelation Therapy
Description	Comparison of average serum creatinine over 12 months of combined chelation therapy compared with baseline serum creatinine.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deferasirox (Exjade) and Desferal (DFO)
Arm/Group Description	Subjects were treated with Deferasirox (Exjade) and Desferal (DFO) with dosing based on baseline iron overload.
Measure Participants	22
Mean (95% Confidence Interval) [mg/dl]	0.09

Adverse Events

Time Frame	1 year
Arm/Group Title	Deferasirox (Exjade) and Deferoxamine (DFO)
Arm/Group Description	Treatment with Deferasirox (Exjade) and Deferoxamine (DFO) with dosing based on baseline iron overload.
All Cause Mortality
	Deferasirox (Exjade) and Deferoxamine (DFO)
	Affected / at Risk (%)	# Events
Total	1/22 (4.5%)
Serious Adverse Events
	Deferasirox (Exjade) and Deferoxamine (DFO)
	Affected / at Risk (%)	# Events
Total	2/22 (9.1%)
Cardiac disorders
Death	1/22 (4.5%)	1
Hepatobiliary disorders
Cholelithiasis	1/22 (4.5%)	1
Infections and infestations
Central venous line infection	1/22 (4.5%)	1
Other (Not Including Serious) Adverse Events
	Deferasirox (Exjade) and Deferoxamine (DFO)
	Affected / at Risk (%)	# Events
Total	1/22 (4.5%)
Blood and lymphatic system disorders
Transfusion reaction	1/22 (4.5%)	1

Limitations/Caveats

[Not Specified]

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.