Trial Outcomes & Findings for Pilot Study for Patients With Poor Response to Deferasirox (NCT NCT00749515)
NCT ID: NCT00749515
Last Updated: 2024-02-12
Results Overview
Area Under the Curve (AUC) 0 to 24 hours post dose
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
15 participants
Primary outcome timeframe
0, 1, 2, 4, 6, 8, 12, and 24 hours post dose
Results posted on
2024-02-12
Participant Flow
Between March 2008 and June 2008, 15 patients were recruited who had transfusional iron overload, and had been on deferasirox for at least 6 months at some point in their chelation history. Ten (10) patients were recruited as inadequate responders and 5 were recruited as control patients with adequate response to deferasirox therapy.
Participant milestones
| Measure |
Inadequate Responders
Patients having a rising ferritin trend over 3 consecutive months, at least one higher than 1500ng/mL (1500 µg/L) or rising liver iron documented by biopsy or change in T2 or Ferriscan magnetic resonance imaging (MRI) and on a dose of more than 30img/kg per day of deferasirox.
|
Adequate Responders (Control)
Patients having a ferritin trend below 1000 ng/mL (1000 µg/L) or documented declining liver iron burden by MRI or biopsy and on a dose of 30img/kg per day or less of deferasirox.
|
|---|---|---|
|
Overall Study
STARTED
|
10
|
5
|
|
Overall Study
COMPLETED
|
10
|
5
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pilot Study for Patients With Poor Response to Deferasirox
Baseline characteristics by cohort
| Measure |
Inadequate Responders
n=10 Participants
Patients having a rising ferritin trend over 3 consecutive months, at least one higher than 1500ng/mL (1500 µg/L) or rising liver iron documented by biopsy or change in T2 or Ferriscan magnetic resonance imaging (MRI) and on a dose of more than 30img/kg per day of deferasirox.
|
Adequate Responders (Control)
n=5 Participants
Patients having a ferritin trend below 1000 ng/mL (1000 µg/L) or documented declining liver iron burden by MRI or biopsy and on a dose of 30img/kg per day or less of deferasirox.
|
Total
n=15 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
7 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=5 Participants
|
5 participants
n=7 Participants
|
15 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 0, 1, 2, 4, 6, 8, 12, and 24 hours post doseArea Under the Curve (AUC) 0 to 24 hours post dose
Outcome measures
| Measure |
Inadequate Responders
n=10 Participants
Patients having a rising ferritin trend over 3 consecutive months, at least one higher than 1500ng/mL (1500 µg/L) or rising liver iron documented by biopsy or change in T2 or Ferriscan magnetic resonance imaging (MRI) and on a dose of more than 30img/kg per day of deferasirox.
|
Adequate Responders (Control)
n=5 Participants
Patients having a ferritin trend below 1000 ng/mL (1000 µg/L) or documented declining liver iron burden by MRI or biopsy and on a dose of 30img/kg per day or less of deferasirox.
|
|---|---|---|
|
Area Under the Curve of Deferasirox After a Dose of 35 mg/kg
|
479.59 micromole/liter*hour
Standard Deviation 259.42
|
1123.11 micromole/liter*hour
Standard Deviation 63.4
|
PRIMARY outcome
Timeframe: 0, 1, 2, 4, 6, 8, 12, and 24 hours post dose.All patients received the same interventions of deferoxamine challenge, deferasirox dose with pharmacokinetic monitoring. Then we compared responses between patients who were known to be slow responders to deferasirox and those who were known to be rapid responders (chelated well). Deferoxamine: After a 3-day washout period from all chelation, all patients have a 12 hour infusion of 50mg/kg of deferoxamine with urine collection and pre and post blood sampling to assess iron and Total Iron Binding Capacity (TIBC) by atomic absorption.
Outcome measures
| Measure |
Inadequate Responders
n=10 Participants
Patients having a rising ferritin trend over 3 consecutive months, at least one higher than 1500ng/mL (1500 µg/L) or rising liver iron documented by biopsy or change in T2 or Ferriscan magnetic resonance imaging (MRI) and on a dose of more than 30img/kg per day of deferasirox.
|
Adequate Responders (Control)
n=5 Participants
Patients having a ferritin trend below 1000 ng/mL (1000 µg/L) or documented declining liver iron burden by MRI or biopsy and on a dose of 30img/kg per day or less of deferasirox.
|
|---|---|---|
|
Half-Life of Deferasirox
|
6.08 hour
Standard Deviation 2.01
|
7.83 hour
Standard Deviation 2.95
|
PRIMARY outcome
Timeframe: 0, 1, 2, 4, 6, 8, 12, and 24 hours post doseVolume of distribution/bioavailability (Vd/F)
Outcome measures
| Measure |
Inadequate Responders
n=10 Participants
Patients having a rising ferritin trend over 3 consecutive months, at least one higher than 1500ng/mL (1500 µg/L) or rising liver iron documented by biopsy or change in T2 or Ferriscan magnetic resonance imaging (MRI) and on a dose of more than 30img/kg per day of deferasirox.
|
Adequate Responders (Control)
n=5 Participants
Patients having a ferritin trend below 1000 ng/mL (1000 µg/L) or documented declining liver iron burden by MRI or biopsy and on a dose of 30img/kg per day or less of deferasirox.
|
|---|---|---|
|
Volume of Distribution/Bioavailability of Deferasirox After a Dose of 35 mg/kg
|
10.33 liter
Standard Deviation 7.42
|
6.5 liter
Standard Deviation 2.67
|
PRIMARY outcome
Timeframe: 0, 1, 2, 4, 6, 8, 12, and 24 hours post doseVolume of distribution/bioavailability (Vd/F), adjusted per kilogram body weight
Outcome measures
| Measure |
Inadequate Responders
n=10 Participants
Patients having a rising ferritin trend over 3 consecutive months, at least one higher than 1500ng/mL (1500 µg/L) or rising liver iron documented by biopsy or change in T2 or Ferriscan magnetic resonance imaging (MRI) and on a dose of more than 30img/kg per day of deferasirox.
|
Adequate Responders (Control)
n=5 Participants
Patients having a ferritin trend below 1000 ng/mL (1000 µg/L) or documented declining liver iron burden by MRI or biopsy and on a dose of 30img/kg per day or less of deferasirox.
|
|---|---|---|
|
Volume of Distribution/Bioavailability of Deferasirox After a Dose of 35 mg/kg
|
0.32 liter/kilogram
Standard Deviation 0.25
|
0.13 liter/kilogram
Standard Deviation 0.05
|
PRIMARY outcome
Timeframe: 0, 1, 2, 4, 6, 8, 12, and 24 hours post dose.Clearance/bioavailability (CL/F)
Outcome measures
| Measure |
Inadequate Responders
n=10 Participants
Patients having a rising ferritin trend over 3 consecutive months, at least one higher than 1500ng/mL (1500 µg/L) or rising liver iron documented by biopsy or change in T2 or Ferriscan magnetic resonance imaging (MRI) and on a dose of more than 30img/kg per day of deferasirox.
|
Adequate Responders (Control)
n=5 Participants
Patients having a ferritin trend below 1000 ng/mL (1000 µg/L) or documented declining liver iron burden by MRI or biopsy and on a dose of 30img/kg per day or less of deferasirox.
|
|---|---|---|
|
Clearance/Bioavailability of Deferasirox in Patients With Poor Response to Deferasirox Compared to Patients With Good Response After a Dose of 35 mg/kg
|
1.30 liter/hour
Standard Deviation .18
|
0.61 liter/hour
Standard Deviation 0.22
|
SECONDARY outcome
Timeframe: 3 monthsPolymorphisms in genes known to be, or potentially involved, in deferasirox disposition: UGT1a1 (including the Gilbert syndrome promoter polymorphism, (TA)nTAA),UGT1a3, BRCP/ABCG2, MRP2/ABCC2. These genes were chosen because deferasirox is primarily eliminated by glucuronidation and subsequent biliary excretion.
Outcome measures
| Measure |
Inadequate Responders
n=10 Participants
Patients having a rising ferritin trend over 3 consecutive months, at least one higher than 1500ng/mL (1500 µg/L) or rising liver iron documented by biopsy or change in T2 or Ferriscan magnetic resonance imaging (MRI) and on a dose of more than 30img/kg per day of deferasirox.
|
Adequate Responders (Control)
n=5 Participants
Patients having a ferritin trend below 1000 ng/mL (1000 µg/L) or documented declining liver iron burden by MRI or biopsy and on a dose of 30img/kg per day or less of deferasirox.
|
|---|---|---|
|
Number of Participants With Polymorphisms in Genes Known to be, or Potentially Involved, in Deferasirox Disposition
UGT1a1
|
10 Participants
|
5 Participants
|
|
Number of Participants With Polymorphisms in Genes Known to be, or Potentially Involved, in Deferasirox Disposition
UGT1a3
|
10 Participants
|
5 Participants
|
|
Number of Participants With Polymorphisms in Genes Known to be, or Potentially Involved, in Deferasirox Disposition
BCRP/ABCG2
|
10 Participants
|
5 Participants
|
|
Number of Participants With Polymorphisms in Genes Known to be, or Potentially Involved, in Deferasirox Disposition
MRP2/ABCC2
|
10 Participants
|
5 Participants
|
Adverse Events
Inadequate Responders
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Adequate Responders (Control)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Ellis Neufeld, MD, PhD
St. Jude Children's Research Hospital
Phone: 901-595-7509
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place