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

NCT ID: NCT01459718

Last Updated: 2019-10-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2014-06-30

Brief 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 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.

Conditions

Transfusion-dependent β-thalassemia Patients; Cardiac Iron Overload

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Deferasirox

Intervention Type: DRUG

20-40 mg/kg/day orally, once daily

Deferoxamine (DFO)

Intervention Type: DRUG

40 mg/kg/day subcutaneous (sc) infusion, 3-4 days per week

Interventions

Deferasirox

20-40 mg/kg/day orally, once daily

Intervention Type: DRUG

Deferoxamine (DFO)

40 mg/kg/day subcutaneous (sc) infusion, 3-4 days per week

Intervention Type: DRUG

Other Intervention Names

ICL670, Exjade; DFO, Desferal

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Athens, GR, Greece

Novartis Investigative Site

Athens, , Greece

Novartis Investigative Site

Athens, , Greece

Novartis Investigative Site

Pátrai, , Greece

Countries

Greece

Other Identifiers

2009-018091-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CICL670AGR02

Identifier Type: -

Identifier Source: org_study_id