Trial Outcomes & Findings for Safety and Efficacy of Deferasirox in Combination With Desferoxamine in β-thalassaemia Patients With Severe Cardiac Iron Overload (NCT NCT01459718)
NCT ID: NCT01459718
Last Updated: 2019-10-23
Results Overview
Complete Response is defined as patients that stop intensive deferasirox -DFO treatment, at any time point during the 24 months of study, based on an improvement in the cardiac Magnetic Resonance Imaging T2 star technique (MRI T2\*) value being \>10ms, and continue to be treated with deferasirox monotherapy without any further need for reverting back to intensive iron chelation treatment during the 24 months of study.
TERMINATED
PHASE2
32 participants
24 months
2019-10-23
Participant Flow
In this open-label, single arm study 31 participants were enrolled (one participant was screened twice and was assigned 2 screening numbers; therefore the number enrolled = 32). Of these enrolled participants, 13 were randomized.
Participant milestones
| Measure |
Deferasirox / Deferasirox + Deferoxamine (DFO)
During Phase A, the induction treatment at entry, participants received Deferasirox -DFO combination. During Phase B, when participants transitioned to less intensive chelation therapy, participants received Deferasirox monotherapy.
|
|---|---|
|
Overall Study
STARTED
|
13
|
|
Overall Study
Safety Analysis Set
|
13
|
|
Overall Study
COMPLETED
|
10
|
|
Overall Study
NOT COMPLETED
|
3
|
Reasons for withdrawal
| Measure |
Deferasirox / Deferasirox + Deferoxamine (DFO)
During Phase A, the induction treatment at entry, participants received Deferasirox -DFO combination. During Phase B, when participants transitioned to less intensive chelation therapy, participants received Deferasirox monotherapy.
|
|---|---|
|
Overall Study
Physician Decision
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Adverse Event
|
1
|
Baseline Characteristics
Safety and Efficacy of Deferasirox in Combination With Desferoxamine in β-thalassaemia Patients With Severe Cardiac Iron Overload
Baseline characteristics by cohort
| Measure |
Deferasirox / Deferasirox + Deferoxamine (DFO)
n=13 Participants
During Phase A, the induction treatment at entry, participants received Deferasirox -DFO combination. During Phase B, when participants transitioned to less intensive chelation therapy, participants received Deferasirox monotherapy.
|
|---|---|
|
Age, Continuous
|
32.7 Years
STANDARD_DEVIATION 4.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 24 monthsPopulation: The full analysis set included all the participants entered in the study with at least a valid post-baseline assessment of the primary efficacy variable.
Complete Response is defined as patients that stop intensive deferasirox -DFO treatment, at any time point during the 24 months of study, based on an improvement in the cardiac Magnetic Resonance Imaging T2 star technique (MRI T2\*) value being \>10ms, and continue to be treated with deferasirox monotherapy without any further need for reverting back to intensive iron chelation treatment during the 24 months of study.
Outcome measures
| Measure |
Deferasirox / Deferasirox + Deferoxamine (DFO)
n=12 Participants
During Phase A, the induction treatment at entry, participants received Deferasirox -DFO combination. During Phase B, when participants transitioned to less intensive chelation therapy, participants received Deferasirox monotherapy.
|
|---|---|
|
Number of Patients Achieving a Complete Response (CR)
|
4 Participants
|
PRIMARY outcome
Timeframe: 24 monthsPopulation: The full analysis set included all the participants entered in the study with at least a valid post-baseline assessment of the primary efficacy variable.
Partial Response is defined as patients that stop intensive deferasirox -DFO treatment at any time point during the 24 months study and transition to receive deferasirox monotherapy, but due to a deterioration in cardiac MRI T2\* to a value \< 10 ms revert back to intensive deferasirox -DFO iron chelation therapy during the 24 months of study.
Outcome measures
| Measure |
Deferasirox / Deferasirox + Deferoxamine (DFO)
n=12 Participants
During Phase A, the induction treatment at entry, participants received Deferasirox -DFO combination. During Phase B, when participants transitioned to less intensive chelation therapy, participants received Deferasirox monotherapy.
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|---|---|
|
Number of Patients Achieving a Partial Response (PR)
|
0 Participants
|
PRIMARY outcome
Timeframe: 24 monthsPopulation: The full analysis set included all the participants entered in the study with at least a valid post-baseline assessment of the primary efficacy variable.
Stable Disease is defined as those patients that never achieved an improvement in the cardiac MRI T2\* to values \>10ms during the 24 months of study.
Outcome measures
| Measure |
Deferasirox / Deferasirox + Deferoxamine (DFO)
n=12 Participants
During Phase A, the induction treatment at entry, participants received Deferasirox -DFO combination. During Phase B, when participants transitioned to less intensive chelation therapy, participants received Deferasirox monotherapy.
|
|---|---|
|
Number of Patients With Stable Disease (SD)
|
8 Participants
|
SECONDARY outcome
Timeframe: Baseline, 6, 12, 18, 24 monthsPopulation: The full analysis set included all the participants entered in the study with at least a valid post-baseline assessment of the primary efficacy variable. Here 'n' number analyzed signifies number of participants evaluable at each time point.
Cardiac iron overload was determined by cardiac MRI T2\*. Cardiac iron overload also was measured by the monthly velocity of heart MRI T2\*.
Outcome measures
| Measure |
Deferasirox / Deferasirox + Deferoxamine (DFO)
n=12 Participants
During Phase A, the induction treatment at entry, participants received Deferasirox -DFO combination. During Phase B, when participants transitioned to less intensive chelation therapy, participants received Deferasirox monotherapy.
|
|---|---|
|
Change From Baseline in Cardiac Iron Overload of Patients in Intensive Iron Chelation Therapy Consisting of Deferasirox-DFO and After Transition to Deferasirox Monotherapy
6 months
|
0.1 Milliseconds (ms)
Standard Deviation 1.4
|
|
Change From Baseline in Cardiac Iron Overload of Patients in Intensive Iron Chelation Therapy Consisting of Deferasirox-DFO and After Transition to Deferasirox Monotherapy
12 months
|
0.7 Milliseconds (ms)
Standard Deviation 1.9
|
|
Change From Baseline in Cardiac Iron Overload of Patients in Intensive Iron Chelation Therapy Consisting of Deferasirox-DFO and After Transition to Deferasirox Monotherapy
18 months
|
1.3 Milliseconds (ms)
Standard Deviation 2.4
|
|
Change From Baseline in Cardiac Iron Overload of Patients in Intensive Iron Chelation Therapy Consisting of Deferasirox-DFO and After Transition to Deferasirox Monotherapy
24 months
|
2.4 Milliseconds (ms)
Standard Deviation 3.9
|
SECONDARY outcome
Timeframe: 24 monthsPopulation: The full analysis set included all participants entered in the study with at least a valid post-baseline assessment of the primary efficacy variable. Here 'N' (overall number of participants analyzed) signifies number of participants evaluable for this outcome measure at the specified time-point.
Time to response was defined as the time from baseline when the participant had severe cardiac iron overload to the time when the participant achieved mild/moderate cardiac overload (T2\*\>10 milliseconds \[ms\]).
Outcome measures
| Measure |
Deferasirox / Deferasirox + Deferoxamine (DFO)
n=5 Participants
During Phase A, the induction treatment at entry, participants received Deferasirox -DFO combination. During Phase B, when participants transitioned to less intensive chelation therapy, participants received Deferasirox monotherapy.
|
|---|---|
|
Time to Response
|
13.0 ms
Standard Deviation 1.1
|
SECONDARY outcome
Timeframe: Baseline, 6, 12, 18, 24 monthsPopulation: The full analysis set included all the participants entered in the study with at least a valid post-baseline assessment of the primary efficacy variable. Here 'n' number analyzed signifies number of participants evaluable at each time point.
Change from baseline in LIC was determined by change in liver MRI T2\*.
Outcome measures
| Measure |
Deferasirox / Deferasirox + Deferoxamine (DFO)
n=12 Participants
During Phase A, the induction treatment at entry, participants received Deferasirox -DFO combination. During Phase B, when participants transitioned to less intensive chelation therapy, participants received Deferasirox monotherapy.
|
|---|---|
|
Change From Baseline in Liver Iron Concentration (LIC)
6 months
|
-5 mg of iron/gram of dry weight of liver
Standard Deviation 7.7
|
|
Change From Baseline in Liver Iron Concentration (LIC)
12 months
|
-10.3 mg of iron/gram of dry weight of liver
Standard Deviation 9.2
|
|
Change From Baseline in Liver Iron Concentration (LIC)
18 months
|
-10.2 mg of iron/gram of dry weight of liver
Standard Deviation 10.7
|
|
Change From Baseline in Liver Iron Concentration (LIC)
24 months
|
-12.4 mg of iron/gram of dry weight of liver
Standard Deviation 10.1
|
SECONDARY outcome
Timeframe: Baseline, 6, 12, 18, 24 monthsPopulation: Full analysis set included all participants entered in study with at least a valid post-baseline assessment of the primary efficacy variable. Here 'N' (overall number of participants analyzed) signifies number of participants evaluable for this outcome measure and 'n' (number analyzed) signifies number of participants evaluable at each time point.
Spearman correlation coefficients between serum ferritin and LIC changes from baseline levels were reported.
Outcome measures
| Measure |
Deferasirox / Deferasirox + Deferoxamine (DFO)
n=11 Participants
During Phase A, the induction treatment at entry, participants received Deferasirox -DFO combination. During Phase B, when participants transitioned to less intensive chelation therapy, participants received Deferasirox monotherapy.
|
|---|---|
|
Correlation Between Change From Baseline in Serum Ferritin and LIC Levels
6 months
|
0.091 Spearman correlation coefficient
|
|
Correlation Between Change From Baseline in Serum Ferritin and LIC Levels
12 months
|
-0.033 Spearman correlation coefficient
|
|
Correlation Between Change From Baseline in Serum Ferritin and LIC Levels
18 months
|
0.347 Spearman correlation coefficient
|
|
Correlation Between Change From Baseline in Serum Ferritin and LIC Levels
24 months
|
0.273 Spearman correlation coefficient
|
SECONDARY outcome
Timeframe: 6, 12, 18, 24 monthsPopulation: The full analysis set included all the participants entered in the study with at least a valid post-baseline assessment of the primary efficacy variable. Here 'n' number analyzed signifies number of participants evaluable at each time point.
LVEF % was measured by cardiac magnetic resonance (CMR).
Outcome measures
| Measure |
Deferasirox / Deferasirox + Deferoxamine (DFO)
n=12 Participants
During Phase A, the induction treatment at entry, participants received Deferasirox -DFO combination. During Phase B, when participants transitioned to less intensive chelation therapy, participants received Deferasirox monotherapy.
|
|---|---|
|
Left Ventricular Ejection Fraction (LVEF)
18 months
|
65.1 Percentage of ejection fraction
Standard Deviation 4.8
|
|
Left Ventricular Ejection Fraction (LVEF)
Baseline
|
65 Percentage of ejection fraction
Standard Deviation 4.4
|
|
Left Ventricular Ejection Fraction (LVEF)
6 months
|
65.4 Percentage of ejection fraction
Standard Deviation 5
|
|
Left Ventricular Ejection Fraction (LVEF)
12 months
|
64.8 Percentage of ejection fraction
Standard Deviation 4.6
|
|
Left Ventricular Ejection Fraction (LVEF)
24 months
|
66.2 Percentage of ejection fraction
Standard Deviation 4.6
|
Adverse Events
Deferasirox / Deferasirox + Deferoxamine (DFO)
Serious adverse events
| Measure |
Deferasirox / Deferasirox + Deferoxamine (DFO)
n=13 participants at risk
During Phase A, the induction treatment at entry, participants received Deferasirox -DFO combination. During Phase B, when participants transitioned to less intensive chelation therapy, participants received Deferasirox monotherapy.
|
|---|---|
|
Blood and lymphatic system disorders
Haemolysis
|
7.7%
1/13
|
|
Cardiac disorders
Cardiac discomfort
|
7.7%
1/13
|
|
Cardiac disorders
Sinus tachycardia
|
7.7%
1/13
|
|
Gastrointestinal disorders
Abdominal discomfort
|
7.7%
1/13
|
|
Gastrointestinal disorders
Abdominal pain
|
7.7%
1/13
|
|
Gastrointestinal disorders
Gastritis
|
7.7%
1/13
|
|
Gastrointestinal disorders
Pancreatitis acute
|
7.7%
1/13
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
7.7%
1/13
|
|
Gastrointestinal disorders
Vomiting
|
7.7%
1/13
|
|
General disorders
Chest pain
|
7.7%
1/13
|
|
General disorders
Fatigue
|
7.7%
1/13
|
|
General disorders
Pyrexia
|
7.7%
1/13
|
|
Immune system disorders
Hypersensitivity
|
7.7%
1/13
|
|
Infections and infestations
Sepsis
|
7.7%
1/13
|
|
Infections and infestations
Urinary tract infection
|
7.7%
1/13
|
|
Renal and urinary disorders
Nephrolithiasis
|
7.7%
1/13
|
|
Renal and urinary disorders
Renal colic
|
15.4%
2/13
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
7.7%
1/13
|
|
Surgical and medical procedures
Lithotripsy
|
7.7%
1/13
|
Other adverse events
| Measure |
Deferasirox / Deferasirox + Deferoxamine (DFO)
n=13 participants at risk
During Phase A, the induction treatment at entry, participants received Deferasirox -DFO combination. During Phase B, when participants transitioned to less intensive chelation therapy, participants received Deferasirox monotherapy.
|
|---|---|
|
Blood and lymphatic system disorders
Thrombocytosis
|
7.7%
1/13
|
|
Cardiac disorders
Angina pectoris
|
7.7%
1/13
|
|
Cardiac disorders
Atrial fibrillation
|
7.7%
1/13
|
|
Cardiac disorders
Sinus tachycardia
|
7.7%
1/13
|
|
Ear and labyrinth disorders
Ear pain
|
7.7%
1/13
|
|
Ear and labyrinth disorders
Hypoacusis
|
7.7%
1/13
|
|
Ear and labyrinth disorders
Tinnitus
|
7.7%
1/13
|
|
Endocrine disorders
Hyperthyroidism
|
7.7%
1/13
|
|
Gastrointestinal disorders
Abdominal discomfort
|
7.7%
1/13
|
|
Gastrointestinal disorders
Abdominal distension
|
7.7%
1/13
|
|
Gastrointestinal disorders
Abdominal pain
|
23.1%
3/13
|
|
Gastrointestinal disorders
Abdominal pain lower
|
15.4%
2/13
|
|
Gastrointestinal disorders
Abdominal pain upper
|
15.4%
2/13
|
|
Gastrointestinal disorders
Constipation
|
15.4%
2/13
|
|
Gastrointestinal disorders
Diarrhoea
|
46.2%
6/13
|
|
Gastrointestinal disorders
Gastric disorder
|
7.7%
1/13
|
|
Gastrointestinal disorders
Gastrointestinal disorder
|
23.1%
3/13
|
|
Gastrointestinal disorders
Nausea
|
15.4%
2/13
|
|
Gastrointestinal disorders
Toothache
|
7.7%
1/13
|
|
Gastrointestinal disorders
Vomiting
|
7.7%
1/13
|
|
General disorders
Chest pain
|
7.7%
1/13
|
|
General disorders
Discomfort
|
7.7%
1/13
|
|
General disorders
Fatigue
|
7.7%
1/13
|
|
General disorders
Gait disturbance
|
7.7%
1/13
|
|
General disorders
Malaise
|
7.7%
1/13
|
|
General disorders
Pyrexia
|
30.8%
4/13
|
|
Immune system disorders
Hypersensitivity
|
15.4%
2/13
|
|
Immune system disorders
Seasonal allergy
|
7.7%
1/13
|
|
Infections and infestations
Abscess
|
7.7%
1/13
|
|
Infections and infestations
Bronchitis
|
7.7%
1/13
|
|
Infections and infestations
Ear infection
|
7.7%
1/13
|
|
Infections and infestations
Gastroenteritis
|
15.4%
2/13
|
|
Infections and infestations
Nasopharyngitis
|
7.7%
1/13
|
|
Infections and infestations
Respiratory tract infection
|
15.4%
2/13
|
|
Infections and infestations
Rhinitis
|
15.4%
2/13
|
|
Infections and infestations
Tooth abscess
|
7.7%
1/13
|
|
Infections and infestations
Upper respiratory tract infection
|
23.1%
3/13
|
|
Infections and infestations
Viral infection
|
15.4%
2/13
|
|
Infections and infestations
Viral upper respiratory tract infection
|
15.4%
2/13
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
7.7%
1/13
|
|
Injury, poisoning and procedural complications
Muscle contusion
|
7.7%
1/13
|
|
Investigations
Blood pressure increased
|
7.7%
1/13
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
38.5%
5/13
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
23.1%
3/13
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
7.7%
1/13
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
7.7%
1/13
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
15.4%
2/13
|
|
Nervous system disorders
Dizziness
|
15.4%
2/13
|
|
Nervous system disorders
Facial neuralgia
|
7.7%
1/13
|
|
Nervous system disorders
Headache
|
30.8%
4/13
|
|
Nervous system disorders
Hypotonia
|
7.7%
1/13
|
|
Nervous system disorders
Presyncope
|
7.7%
1/13
|
|
Nervous system disorders
Sciatica
|
7.7%
1/13
|
|
Nervous system disorders
Syncope
|
7.7%
1/13
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
7.7%
1/13
|
|
Reproductive system and breast disorders
Genital burning sensation
|
7.7%
1/13
|
|
Reproductive system and breast disorders
Menstrual disorder
|
7.7%
1/13
|
|
Respiratory, thoracic and mediastinal disorders
Catarrh
|
23.1%
3/13
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
30.8%
4/13
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
7.7%
1/13
|
|
Respiratory, thoracic and mediastinal disorders
Paranasal sinus discomfort
|
7.7%
1/13
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
7.7%
1/13
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
7.7%
1/13
|
|
Skin and subcutaneous tissue disorders
Photosensitivity reaction
|
7.7%
1/13
|
|
Surgical and medical procedures
Tooth extraction
|
15.4%
2/13
|
|
Surgical and medical procedures
Tooth repair
|
7.7%
1/13
|
|
Surgical and medical procedures
Wisdom teeth removal
|
7.7%
1/13
|
Additional Information
Study Director
Novartis Pharmaceuticals
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