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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Number of Patients Achieving a Complete Response (CR)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Deferasirox (Drug)
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.
干预措施: Deferoxamine (DFO) (Drug)
结局指标
主要结局
Number of Patients Achieving a Complete Response (CR)
时间窗: 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 With Stable Disease (SD)
时间窗: 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.
Number of Patients Achieving a Partial Response (PR)
时间窗: 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.
次要结局
- Time to Response(24 months)
- Correlation Between Change From Baseline in Serum Ferritin and LIC Levels(Baseline, 6, 12, 18, 24 months)
- Change From Baseline in Cardiac Iron Overload of Patients in Intensive Iron Chelation Therapy Consisting of Deferasirox-DFO and After Transition to Deferasirox Monotherapy(Baseline, 6, 12, 18, 24 months)
- Change From Baseline in Liver Iron Concentration (LIC)(Baseline, 6, 12, 18, 24 months)
- Left Ventricular Ejection Fraction (LVEF)(6, 12, 18, 24 months)