Safety and Efficacy of Deferasirox in Combination With Desferoxamine in β-thalassaemia Patients With Severe Cardiac Iron Overload
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|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
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|Condition or disease||Intervention/treatment||Phase|
|Transfusion-dependent β-thalassemia Patients Cardiac Iron Overload||Drug: Deferasirox Drug: Deferoxamine (DFO)||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multicenter Open Label Phase II Study to Evaluate the Safety and Efficacy of Deferasirox in Combination With Deferoxamine Followed by Transitioning to Deferasirox Monotherapy in β-thalassemia Patients With Severe Cardiac Iron Overload|
|Study Start Date :||January 2011|
|Actual Primary Completion Date :||June 2014|
|Actual Study Completion Date :||June 2014|
Experimental: 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.
20-40 mg/kg/day orally, once daily
Other Name: ICL670, Exjade
Drug: Deferoxamine (DFO)
40 mg/kg/day subcutaneous (sc) infusion, 3-4 days per week
Other Name: DFO, Desferal
- Number of Patients Achieving a Complete Response (CR) [ Time Frame: 24 months ]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.
- Number of Patients Achieving a Partial Response (PR) [ Time Frame: 24 months ]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.
- Number of Patients With Stable Disease (SD) [ Time Frame: 24 months ]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.
- Change From Baseline in Cardiac Iron Overload of Patients in Intensive Iron Chelation Therapy Consisting of Deferasirox-DFO and After Transition to Deferasirox Monotherapy [ Time Frame: Baseline, 6, 12, 18, 24 months ]Cardiac iron overload was determined by cardiac MRI T2*. Cardiac iron overload also was measured by the monthly velocity of heart MRI T2*.
- Time to Response [ Time Frame: 24 months ]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]).
- Change From Baseline in Liver Iron Concentration (LIC) [ Time Frame: Baseline, 6, 12, 18, 24 months ]Change from baseline in LIC was determined by change in liver MRI T2*.
- Correlation Between Change From Baseline in Serum Ferritin and LIC Levels [ Time Frame: Baseline, 6, 12, 18, 24 months ]Spearman correlation coefficients between serum ferritin and LIC changes from baseline levels were reported.
- Left Ventricular Ejection Fraction (LVEF) [ Time Frame: 6, 12, 18, 24 months ]LVEF % was measured by cardiac magnetic resonance (CMR).
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Male or female patients with β-thalassemia major, at least 18 years old, having given written consent to participate in the study.
- Cardiac MRI T2* value ranging from <=4 to <=10 ms.
- LVEF ≥ 56 % as determined by CMR.
- Patients with LIC > 10mg Fe/g dw will be included in the protocol. Study will evaluate the first 10 patients at 6 months, and if no safety signals are present, patients with LIC>5 mg Fe/g dw will be allowed to be included.
- Prior iron chelation treatment with DFO, DFP, DFX or combination DFO-DFP
- Patients with symptoms of cardiac dysfunction symptoms (shortness of breath at rest or exertion, orthopnea, exercise intolerance, lower extremity edema, arrhythmias).
- Patients with cardiac T2* MRI < 4 or > 10 ms.
- Patients not compliant to intensive iron chelation therapy regimens such i.v DFO 24 hr infusions or DFO-DFP combination.
- Patients with documented liver failure (presence of portal hypertension, hepatic edemas, ascites).
- Patients unable to undergo study assessments, including blood sampling, MRI, e.g., are claustrophobic to MRI, have a pacemaker, ferromagnetic metal implants other than those approved as safe for use in MRI scanners (e.g., some types of aneurysm clips, shrapnel in proximity to vital organs such as the retina), are obese (exceeding the equipment limits).
- Patients with serum creatinine > ULN or with significant proteinuria as indicated by a urinary protein/creatinine ratio ≥ 1.0 in a non-first void urine sample at baseline. Patients with creatinine clearance <60 ml/min will be excluded.
- Patients with ALT (SGPT) levels > 5 x ULN.
- Patients with considerable impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral deferasirox / ICL670 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection.
- History or clinical evidence of pancreatic injury or pancreatitis.
- Patients with a known hypersensitivity to any of the study drugs or the drug's excipients.
- History of clinically relevant ocular and/or auditor toxicity related to iron chelation therapy.
- Patients with psychiatric or addictive disorders which prevent them from giving their informed consent or undergoing any of the treatment options or patients unwilling or unable to comply with the protocol.
- Patients with a known history of HIV seropositivity (Elisa or Western blot).
- History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.
- Female patients who are pregnant or breast feeding.
- Female patients of reproductive potential not employing an effective method of birth control. Women of childbearing potential must have a negative serum pregnancy test ≤ 48 hours prior to the study drugs.
- Patients participating in another clinical trial or receiving an investigational drug.
- History of non-compliance with medical regimens or patients who are considered potentially unreliable and/or not cooperative, unwilling or unable to comply with the protocol.
Other protocol-defined inclusion/exclusion criteria may apply
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01459718
|Novartis Investigative Site|
|Athens, GR, Greece, GR-115 27|
|Novartis Investigative Site|
|Athens, Greece, 11527|
|Novartis Investigative Site|
|Athens, Greece, GR|
|Novartis Investigative Site|
|Patras, Greece, 265 00|
|Study Director:||Novartis Pharmaceuticals||Novartis Pharmaceuticals|
|Responsible Party:||Novartis Pharmaceuticals|
|Other Study ID Numbers:||
2009-018091-34 ( EudraCT Number )
|First Posted:||October 26, 2011 Key Record Dates|
|Results First Posted:||October 23, 2019|
|Last Update Posted:||October 23, 2019|
|Last Verified:||October 2019|
Severe cardiac iron overload
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Iron Metabolism Disorders
Iron Chelating Agents
Molecular Mechanisms of Pharmacological Action