Don't get left behind! The modernized ClinicalTrials.gov is coming. Check it out now.
Say goodbye to ClinicalTrials.gov!
The new site is coming soon - go to the modernized ClinicalTrials.gov
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Efficacy of Deferasirox in Combination With Desferoxamine in β-thalassaemia Patients With Severe Cardiac Iron Overload

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01459718
Recruitment Status : Terminated (The study terminated due to low enrollment.)
First Posted : October 26, 2011
Results First Posted : October 23, 2019
Last Update Posted : October 23, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Transfusion-dependent β-thalassemia Patients
Cardiac Iron Overload
Interventions Drug: Deferasirox
Drug: Deferoxamine (DFO)
Enrollment 32
Recruitment Details 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.
Pre-assignment Details  
Arm/Group Title Deferasirox / Deferasirox + Deferoxamine (DFO)
Hide Arm/Group Description 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.
Period Title: Overall Study
Started 13
Safety Analysis Set 13
Completed 10
Not Completed 3
Reason Not Completed
Physician Decision             1
Lost to Follow-up             1
Adverse Event             1
Arm/Group Title Deferasirox / Deferasirox + Deferoxamine (DFO)
Hide Arm/Group Description 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 Number of Baseline Participants 13
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 13 participants
32.7  (4.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants
Female
8
  61.5%
Male
5
  38.5%
1.Primary Outcome
Title Number of Patients Achieving a Complete Response (CR)
Hide Description 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.
Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Deferasirox / Deferasirox + Deferoxamine (DFO)
Hide Arm/Group Description:
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 Number of Participants Analyzed 12
Measure Type: Count of Participants
Unit of Measure: Participants
4
  33.3%
2.Primary Outcome
Title Number of Patients Achieving a Partial Response (PR)
Hide Description 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.
Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Deferasirox / Deferasirox + Deferoxamine (DFO)
Hide Arm/Group Description:
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 Number of Participants Analyzed 12
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
3.Primary Outcome
Title Number of Patients With Stable Disease (SD)
Hide Description 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.
Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Deferasirox / Deferasirox + Deferoxamine (DFO)
Hide Arm/Group Description:
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 Number of Participants Analyzed 12
Measure Type: Count of Participants
Unit of Measure: Participants
8
  66.7%
4.Secondary Outcome
Title Change From Baseline in Cardiac Iron Overload of Patients in Intensive Iron Chelation Therapy Consisting of Deferasirox-DFO and After Transition to Deferasirox Monotherapy
Hide Description Cardiac iron overload was determined by cardiac MRI T2*. Cardiac iron overload also was measured by the monthly velocity of heart MRI T2*.
Time Frame Baseline, 6, 12, 18, 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Deferasirox / Deferasirox + Deferoxamine (DFO)
Hide Arm/Group Description:
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 Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: Milliseconds (ms)
6 months Number Analyzed 12 participants
0.1  (1.4)
12 months Number Analyzed 10 participants
0.7  (1.9)
18 months Number Analyzed 11 participants
1.3  (2.4)
24 months Number Analyzed 10 participants
2.4  (3.9)
5.Secondary Outcome
Title Time to Response
Hide Description 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]).
Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Deferasirox / Deferasirox + Deferoxamine (DFO)
Hide Arm/Group Description:
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 Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: ms
13.0  (1.1)
6.Secondary Outcome
Title Change From Baseline in Liver Iron Concentration (LIC)
Hide Description Change from baseline in LIC was determined by change in liver MRI T2*.
Time Frame Baseline, 6, 12, 18, 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Deferasirox / Deferasirox + Deferoxamine (DFO)
Hide Arm/Group Description:
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 Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: mg of iron/gram of dry weight of liver
6 months Number Analyzed 12 participants
-5  (7.7)
12 months Number Analyzed 10 participants
-10.3  (9.2)
18 months Number Analyzed 11 participants
-10.2  (10.7)
24 months Number Analyzed 10 participants
-12.4  (10.1)
7.Secondary Outcome
Title Correlation Between Change From Baseline in Serum Ferritin and LIC Levels
Hide Description Spearman correlation coefficients between serum ferritin and LIC changes from baseline levels were reported.
Time Frame Baseline, 6, 12, 18, 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Deferasirox / Deferasirox + Deferoxamine (DFO)
Hide Arm/Group Description:
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 Number of Participants Analyzed 11
Measure Type: Number
Unit of Measure: Spearman correlation coefficient
6 months Number Analyzed 11 participants
0.091
12 months Number Analyzed 9 participants
-0.033
18 months Number Analyzed 11 participants
0.347
24 months Number Analyzed 10 participants
0.273
8.Secondary Outcome
Title Left Ventricular Ejection Fraction (LVEF)
Hide Description LVEF % was measured by cardiac magnetic resonance (CMR).
Time Frame 6, 12, 18, 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Deferasirox / Deferasirox + Deferoxamine (DFO)
Hide Arm/Group Description:
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 Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: Percentage of ejection fraction
Baseline Number Analyzed 12 participants
65  (4.4)
6 months Number Analyzed 12 participants
65.4  (5)
12 months Number Analyzed 10 participants
64.8  (4.6)
18 months Number Analyzed 11 participants
65.1  (4.8)
24 months Number Analyzed 10 participants
66.2  (4.6)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Deferasirox / Deferasirox + Deferoxamine (DFO)
Hide Arm/Group Description 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.
All-Cause Mortality
Deferasirox / Deferasirox + Deferoxamine (DFO)
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
Deferasirox / Deferasirox + Deferoxamine (DFO)
Affected / at Risk (%)
Total   5/13 (38.46%) 
Blood and lymphatic system disorders   
Haemolysis † 1  1/13 (7.69%) 
Cardiac disorders   
Cardiac discomfort † 1  1/13 (7.69%) 
Sinus tachycardia † 1  1/13 (7.69%) 
Gastrointestinal disorders   
Abdominal discomfort † 1  1/13 (7.69%) 
Abdominal pain † 1  1/13 (7.69%) 
Gastritis † 1  1/13 (7.69%) 
Pancreatitis acute † 1  1/13 (7.69%) 
Rectal haemorrhage † 1  1/13 (7.69%) 
Vomiting † 1  1/13 (7.69%) 
General disorders   
Chest pain † 1  1/13 (7.69%) 
Fatigue † 1  1/13 (7.69%) 
Pyrexia † 1  1/13 (7.69%) 
Immune system disorders   
Hypersensitivity † 1  1/13 (7.69%) 
Infections and infestations   
Sepsis † 1  1/13 (7.69%) 
Urinary tract infection † 1  1/13 (7.69%) 
Renal and urinary disorders   
Nephrolithiasis † 1  1/13 (7.69%) 
Renal colic † 1  2/13 (15.38%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnoea † 1  1/13 (7.69%) 
Surgical and medical procedures   
Lithotripsy † 1  1/13 (7.69%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Deferasirox / Deferasirox + Deferoxamine (DFO)
Affected / at Risk (%)
Total   12/13 (92.31%) 
Blood and lymphatic system disorders   
Thrombocytosis † 1  1/13 (7.69%) 
Cardiac disorders   
Angina pectoris † 1  1/13 (7.69%) 
Atrial fibrillation † 1  1/13 (7.69%) 
Sinus tachycardia † 1  1/13 (7.69%) 
Ear and labyrinth disorders   
Ear pain † 1  1/13 (7.69%) 
Hypoacusis † 1  1/13 (7.69%) 
Tinnitus † 1  1/13 (7.69%) 
Endocrine disorders   
Hyperthyroidism † 1  1/13 (7.69%) 
Gastrointestinal disorders   
Abdominal discomfort † 1  1/13 (7.69%) 
Abdominal distension † 1  1/13 (7.69%) 
Abdominal pain † 1  3/13 (23.08%) 
Abdominal pain lower † 1  2/13 (15.38%) 
Abdominal pain upper † 1  2/13 (15.38%) 
Constipation † 1  2/13 (15.38%) 
Diarrhoea † 1  6/13 (46.15%) 
Gastric disorder † 1  1/13 (7.69%) 
Gastrointestinal disorder † 1  3/13 (23.08%) 
Nausea † 1  2/13 (15.38%) 
Toothache † 1  1/13 (7.69%) 
Vomiting † 1  1/13 (7.69%) 
General disorders   
Chest pain † 1  1/13 (7.69%) 
Discomfort † 1  1/13 (7.69%) 
Fatigue † 1  1/13 (7.69%) 
Gait disturbance † 1  1/13 (7.69%) 
Malaise † 1  1/13 (7.69%) 
Pyrexia † 1  4/13 (30.77%) 
Immune system disorders   
Hypersensitivity † 1  2/13 (15.38%) 
Seasonal allergy † 1  1/13 (7.69%) 
Infections and infestations   
Abscess † 1  1/13 (7.69%) 
Bronchitis † 1  1/13 (7.69%) 
Ear infection † 1  1/13 (7.69%) 
Gastroenteritis † 1  2/13 (15.38%) 
Nasopharyngitis † 1  1/13 (7.69%) 
Respiratory tract infection † 1  2/13 (15.38%) 
Rhinitis † 1  2/13 (15.38%) 
Tooth abscess † 1  1/13 (7.69%) 
Upper respiratory tract infection † 1  3/13 (23.08%) 
Viral infection † 1  2/13 (15.38%) 
Viral upper respiratory tract infection † 1  2/13 (15.38%) 
Injury, poisoning and procedural complications   
Arthropod bite † 1  1/13 (7.69%) 
Muscle contusion † 1  1/13 (7.69%) 
Investigations   
Blood pressure increased † 1  1/13 (7.69%) 
Musculoskeletal and connective tissue disorders   
Arthralgia † 1  5/13 (38.46%) 
Back pain † 1  3/13 (23.08%) 
Bone pain † 1  1/13 (7.69%) 
Musculoskeletal pain † 1  1/13 (7.69%) 
Myalgia † 1  2/13 (15.38%) 
Nervous system disorders   
Dizziness † 1  2/13 (15.38%) 
Facial neuralgia † 1  1/13 (7.69%) 
Headache † 1  4/13 (30.77%) 
Hypotonia † 1  1/13 (7.69%) 
Presyncope † 1  1/13 (7.69%) 
Sciatica † 1  1/13 (7.69%) 
Syncope † 1  1/13 (7.69%) 
Reproductive system and breast disorders   
Dysmenorrhoea † 1  1/13 (7.69%) 
Genital burning sensation † 1  1/13 (7.69%) 
Menstrual disorder † 1  1/13 (7.69%) 
Respiratory, thoracic and mediastinal disorders   
Catarrh † 1  3/13 (23.08%) 
Cough † 1  4/13 (30.77%) 
Dysphonia † 1  1/13 (7.69%) 
Paranasal sinus discomfort † 1  1/13 (7.69%) 
Respiratory distress † 1  1/13 (7.69%) 
Rhinitis allergic † 1  1/13 (7.69%) 
Skin and subcutaneous tissue disorders   
Photosensitivity reaction † 1  1/13 (7.69%) 
Surgical and medical procedures   
Tooth extraction † 1  2/13 (15.38%) 
Tooth repair † 1  1/13 (7.69%) 
Wisdom teeth removal † 1  1/13 (7.69%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Study was terminated. Efficacy was not powered for analysis due to the low enrollment of only 13 patients.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-1873
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01459718    
Other Study ID Numbers: CICL670AGR02
2009-018091-34 ( EudraCT Number )
First Submitted: July 20, 2011
First Posted: October 26, 2011
Results First Submitted: July 28, 2015
Results First Posted: October 23, 2019
Last Update Posted: October 23, 2019