Transfusion-dependent β-thalassemia PatientsPhase 2NCT01459718
Safety and Efficacy of Deferasirox in Combination With Desferoxamine in β-thalassaemia Patients With Severe Cardiac Iron Overload
A Phase 2 study testing Deferasirox and Deferoxamine (DFO) in people with Transfusion-dependent β-thalassemia Patients and Cardiac Iron Overload, run by Novartis Pharmaceuticals at 4 sites in Greece.
Trial summary
The primary efficacy endpoint of this interventional study was to evaluate the number of patients achieving a complete response (CR), defined as patients switching from intensive deferasirox -DFO treatment, at any time point during the 24 months of study, to deferasirox monotherapy based on improvement in the cardiac… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Transfusion-dependent β-thalassemia Patients, Cardiac Iron Overload
- What is being tested?
- Deferasirox and Deferoxamine (DFO)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 4 sitesGreece
- Study dates
- Jan 2011to Jun 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
4 sites in 1 country.
Greece4 sites
Novartis Investigative Site
Athens, GR, GR-115 27
Novartis Investigative Site
Athens, 11527
Novartis Investigative Site
Athens, GR
Novartis Investigative Site
Pátrai, 265 00
About this study
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
The primary efficacy endpoint of this interventional study was to evaluate the number of patients achieving a complete response (CR), defined as patients switching from intensive deferasirox -DFO treatment, at any time point during the 24 months of study, to deferasirox monotherapy based on improvement in the cardiac magnetic resonance imaging (MRI) T2* value to >10ms, and continue to maintain their MRI T2* to values >10 msec.
Read the detailed description
This study was planned to recruit 52 transfusion-dependent β-thalassemia patients with severe cardiac iron overload. However only 13 patients participated in the study during a 3 year and 5 month timeframe. The study was terminated due to the slow enrollment rate due to scarcity of the patient population with severe cardiac iron overload.
- Being tested
- Deferasirox, Deferoxamine (DFO)
- Keywords
- Severe cardiac iron overload, deferasirox, β-thalassaemia, cardiac dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DeferasiroxDrug
Also called ICL670, Exjade
20-40 mg/kg/day orally, once daily
Deferoxamine (DFO)Drug
Also called DFO, Desferal
40 mg/kg/day subcutaneous (sc) infusion, 3-4 days per week
| Study group | Role | What they receive |
|---|---|---|
| Deferasirox / Deferasirox + Deferoxamine (DFO) | Experimental | 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. Receives: Drug: Deferasirox; Drug: Deferoxamine (DFO) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Achieving a Complete Response (CR)
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.
Measured: 24 months
Number of Patients Achieving a Partial Response (PR)
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.
Measured: 24 months
Number of Patients With Stable Disease (SD)
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.
Measured: 24 months
Secondary outcomes (5)
Change From Baseline in Cardiac Iron Overload of Patients in Intensive Iron Chelation Therapy Consisting of Deferasirox-DFO and After Transition to Deferasirox Monotherapy
Cardiac iron overload was determined by cardiac MRI T2*. Cardiac iron overload also was measured by the monthly velocity of heart MRI T2*.
Measured: Baseline, 6, 12, 18, 24 months
Time to Response
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]).
Measured: 24 months
Change From Baseline in Liver Iron Concentration (LIC)
Change from baseline in LIC was determined by change in liver MRI T2*.
Measured: Baseline, 6, 12, 18, 24 months
Correlation Between Change From Baseline in Serum Ferritin and LIC Levels
Spearman correlation coefficients between serum ferritin and LIC changes from baseline levels were reported.
Measured: Baseline, 6, 12, 18, 24 months
Left Ventricular Ejection Fraction (LVEF)
LVEF % was measured by cardiac magnetic resonance (CMR).
Measured: 6, 12, 18, 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2011 (estimated)
- Study startJan 2011
- Primary completionJun 2014
- Study completionJun 2014
Why it stopped: The study terminated due to low enrollment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Transfusion-dependent β-thalassemia PatientsStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01459718
- Sponsor's protocol ID
- CICL670AGR02
- Other IDs
- 2009-018091-34, 2009
- Status last verified
- Oct 2019
- First submitted
- 20 Jul 2011
- Last updated
- 23 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01459718
- Acronym / sponsor ID
- CICL670AGR02
- Keywords
- Severe cardiac iron overload, deferasirox, β-thalassaemia, cardiac dysfunction
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study terminated due to low enrollment.
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jan 2011
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 26 Oct 2011 (estimated)
- Results
- Posted 23 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary efficacy endpoint of this interventional study was to evaluate the number of patients achieving a complete response (CR), defined as patients switching from intensive deferasirox -DFO treatment, at any time point during the 24 months of study, to deferasirox monotherapy based on improvement in the cardiac magnetic resonance imaging (MRI) T2* value to >10ms, and continue to maintain their MRI T2* to values >10 msec.
Detailed description
This study was planned to recruit 52 transfusion-dependent β-thalassemia patients with severe cardiac iron overload. However only 13 patients participated in the study during a 3 year and 5 month timeframe. The study was terminated due to the slow enrollment rate due to scarcity of the patient population with severe cardiac iron overload.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Deferasirox / Deferasirox + Deferoxamine (DFO) | Experimental | Drug: Deferasirox, Drug: 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (19 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DeferasiroxAlso: ICL670, Exjade20-40 mg/kg/day orally, once daily | Drug | Deferasirox / Deferasirox + Deferoxamine (DFO) |
| Deferoxamine (DFO)Also: DFO, Desferal40 mg/kg/day subcutaneous (sc) infusion, 3-4 days per week | Drug | Deferasirox / Deferasirox + Deferoxamine (DFO) |
Primary outcome
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.
5 secondary outcomes
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
Time to Response
Time frame: 24 months
Change From Baseline in Liver Iron Concentration (LIC)
Time frame: Baseline, 6, 12, 18, 24 months
Correlation Between Change From Baseline in Serum Ferritin and LIC Levels
Time frame: Baseline, 6, 12, 18, 24 months
Left Ventricular Ejection Fraction (LVEF)
Time frame: 6, 12, 18, 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Deferasirox and Deferoxamine (DFO) in people with Transfusion-dependent β-thalassemia Patients and Cardiac Iron Overload, run by Novartis Pharmaceuticals at 4 sites in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients Achieving a Complete Response (CR) (time frame: 24 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2019.