Trial Outcomes & Findings for Post Hematopoietic Stem Cell Transplantation (NCT NCT01610297)

Last Updated: 2016-10-24

Results Overview

To determine the safety; incidence, type and severity of adverse events including renal, hepatic, biochemistry and hematologic parameters of deferasirox in the treatment of iron overload after hematopoietic stem cell transplantation (HSCT) in patients with beta-thalassemia major in 12 months period

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

27 participants

Primary outcome timeframe

12 months

Results posted on

2016-10-24

Participant Flow

Participant milestones

Participant milestones
Measure	ICL670 Oral dose of ICL670 at 10 mg/kg daily
Overall Study STARTED	27
Overall Study COMPLETED	26
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	ICL670 Oral dose of ICL670 at 10 mg/kg daily
Overall Study Lost to Follow-up	1

Baseline Characteristics

Post Hematopoietic Stem Cell Transplantation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ICL670 n=27 Participants Oral dose of ICL670 at 10 mg/kg daily
Age, Continuous	9.07 years STANDARD_DEVIATION 3.81 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Population: The Safety Set (SS) includes all included patients who were included in the study. All statistical analyses of safety and tolerability will be done in the SS.

Outcome measures

Outcome measures
Measure	ICL670 n=27 Participants Oral dose of ICL670 at 10 mg/kg daily
Number of Participants With Adverse Events, Serious Adverse Events and Deaths as a Measure of Safety and Tolerability Adverse events	25 Participants
Number of Participants With Adverse Events, Serious Adverse Events and Deaths as a Measure of Safety and Tolerability Serious adverse events	3 Participants
Number of Participants With Adverse Events, Serious Adverse Events and Deaths as a Measure of Safety and Tolerability Death	0 Participants

SECONDARY outcome

Timeframe: Baseline, 12 Months

Population: The Full Analysis Set (FAS) comprises all patients in whom study treatment has been started and received at least one dose.

Blood samples were collected and serum levels were assessed at study baseline (BL) and at 12 months.

Outcome measures

Outcome measures
Measure	ICL670 n=27 Participants Oral dose of ICL670 at 10 mg/kg daily
Change in Serum Ferritin Level. Baseline	1766.81 ng/mL Standard Deviation 599.64
Change in Serum Ferritin Level. Month 12	903.56 ng/mL Standard Deviation 596.62

SECONDARY outcome

Timeframe: Baseline, 12 month

Population: The Full Analysis Set (FAS) comprises all patients in whom study treatment has been started and received at least one dose.

Liver Iron Concentration (LIC) values between 3 and 7 mg Fe / g dry weight are indicative of mild iron deposition, while values between 7 and 15 mg Fe / g dry weight are indicative of moderate iron deposition which have been associated with liver disease. Values \>15 mg Fe/g dry weight are indicative of severe iron deposition which is associated with progressive liver fibrosis, increased morbidity and mortality

Outcome measures

Outcome measures
Measure	ICL670 n=27 Participants Oral dose of ICL670 at 10 mg/kg daily
Change in the Further Parameters of Iron Overload (Liver Iron Concentration by Magnetic Resonance Imaging (MRI Examination) Baseline Liver MRI(n= 27)	12.07 mg Fe/g dry liver weight Standard Deviation 9.42
Change in the Further Parameters of Iron Overload (Liver Iron Concentration by Magnetic Resonance Imaging (MRI Examination) Week 52 Liver MRI (n=25)	4.62 mg Fe/g dry liver weight Standard Deviation 2.85

SECONDARY outcome

Timeframe: Week 28 and Week 52

Population: The Full Analysis Set (FAS) comprises all patients in whom study treatment has been started and received at least one dose.

Serum Ferritin values between 1000-2500 μg/L are indicative of mild to moderate iron overload while values \>2500 μg/L are indicative of severe iron overload and levels constantly higher than 2500 μg/L has been shown to to increase the risk of cardiac complications and endocrine disease. Maintaining levels \<1000 μg/L is associated with increased survival and less morbidity.

Outcome measures

Outcome measures
Measure	ICL670 n=27 Participants Oral dose of ICL670 at 10 mg/kg daily
The Percentage of Patients Reaching Serum Ferritin Levels Lower Than 500 μg/L Week 28 (n=26)	7.7 Percentage of Patients
The Percentage of Patients Reaching Serum Ferritin Levels Lower Than 500 μg/L Week 52 (n=27)	33.3 Percentage of Patients

SECONDARY outcome

Timeframe: Baseline, 12 month

Population: The Full Analysis Set (FAS) comprises all patients in whom study treatment has been started and received at least one dose.

Cardiac MRI values between 10 to 20 milliseconds (ms) are indicative of moderate cardiac iron deposition associated with declining left ventricular ejection fraction and arrhythmias while values \<10 ms are indicative of deposition sufficient to risk cardiac decompensation and associated with overt heart failure and mortality.

Outcome measures

Outcome measures
Measure	ICL670 n=27 Participants Oral dose of ICL670 at 10 mg/kg daily
Change in the Further Parameters of Iron Overload (Cardiac Iron Concentration by Magnetic Resonance Imaging (MRI Examination) Week 52 Cardiac MRI (n=24)	28.25 ms Standard Deviation 5.53
Change in the Further Parameters of Iron Overload (Cardiac Iron Concentration by Magnetic Resonance Imaging (MRI Examination) Baseline Cardiac MRI(n= 27)	26.48 ms Standard Deviation 7.49

Adverse Events

ICL670

Serious events: 3 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ICL670 n=27 participants at risk Oral dose of ICL670 at 10 mg/kg daily
Investigations Neutrophil count decreased	7.4% 2/27
Investigations Alanine aminotransferase increased	3.7% 1/27
Investigations Aspartate aminotransferase increased	3.7% 1/27
General disorders Influenza like illness	3.7% 1/27
Surgical and medical procedures Office visit	3.7% 1/27
Hepatobiliary disorders Hepatitis B	3.7% 1/27

Other adverse events

Other adverse events
Measure	ICL670 n=27 participants at risk Oral dose of ICL670 at 10 mg/kg daily
Blood and lymphatic system disorders Anemia	25.9% 7/27
Respiratory, thoracic and mediastinal disorders Cough	25.9% 7/27
General disorders Pyrexia	25.9% 7/27
Investigations Aspartate aminotransferase increased	22.2% 6/27
Infections and infestations Pharyngitis	22.2% 6/27
Respiratory, thoracic and mediastinal disorders Influenza	18.5% 5/27
Gastrointestinal disorders Diarrhea	11.1% 3/27
Gastrointestinal disorders Vomiting	11.1% 3/27
Investigations White blood cell count decreased	7.4% 2/27
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	7.4% 2/27
Skin and subcutaneous tissue disorders Eczema	7.4% 2/27
Infections and infestations Haemophilus infection	7.4% 2/27
Infections and infestations Herpes zoster	7.4% 2/27
Immune system disorders Hypersensitivity	7.4% 2/27
Infections and infestations Infection	7.4% 2/27
Respiratory, thoracic and mediastinal disorders Rhinorrhea	7.4% 2/27
Infections and infestations Sinusitis	7.4% 2/27
Investigations Alanine aminotransferase increased	25.9% 7/27
General disorders Influenza like illness	7.4% 2/27

Additional Information

Study Director

Novartis

Phone: 862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Publication restrictions are in place

Restriction type: OTHER