myelodysplastic syndrome and transfusion-dependent iron overload MedDRA version: 8.1 Level: LLT Classification code 10028533 Term: Myelodysplastic syndrome
Conditions
Sponsors
Novartis Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • MDS patients presenting with low or intermediate-1 IPSS risk and transfusional iron overload as shown by a serum ferritin level of > 1000 ng/ml. This level should have been verified at least at two occasions within 6 months before giving informed consent and the time window between these two measurements must have been at least 4 weeks. Samples must be obtained in the absence of concomitant infection • Patients of either gender and age > 18 years • Life expectancy > 12 months • History of at least 20 units of red blood cell transfusions or 100mL/kg of prepacked red blood cells (PRBCs) • Patients can be either naïve to iron chelation or have had prior treatment with deferoxamine (DFO) or deferiprone (L1) • Females of childbearing potential must use double-barrier contraception, oral contraceptive plus barrier contraceptive, or must have undergone clinically documented total hysterectomy and/or oophorectomy, tubal ligation or be postmenopausal defined by amenorrhea for at least 12 months. Only contraception with a pearl-index below 1% should be considered. • Written informed consent by the patient Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Non-transfusion related hemosiderosis • Treatment with ICL670 before study start • Patients with a concomitant malignant disease • Patients with mean levels of alanine aminotransferase (ALT) > 5x ULN • Patients with uncontrolled systemic hypertension • Patients with serum creatinine > 1.5x the upper limit of normal (ULN) • History of nephrotic syndrome • Patients with a previous history of clinically relevant ocular toxicity related to iron chelation • Systemic diseases (cardiovascular, renal, hepatic, etc.) which would prevent the patient from undergoing study treatment • Patients with psychiatric or addictive disorders which prevent them from giving their informed consent or undergoing study treatment • Patients treated with systemic investigational drugs within the past 4 weeks or topical investigational drug within the past 7 days • Any other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug. The investigator should be guided by evidence of any of the following: • history of inflammatory bowel syndrome, gastritis, ulcers, gastrointestinal or rectal bleeding; • history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection; • history of pancreatic injury or pancreatitis; indications of impaired pancreatic function/injury as indicated by abnormal lipase or amylase; • history of urinary obstruction or difficulty in voiding • History of non-compliance to medical regimens and patients who are considered potentially unreliable and/or not cooperative • History of drug or alcohol abuse within the 12 months prior to dosing or evidence of such abuse as indicated by the laboratory assays conducted during the run-in period • Patients with active uncontrolled infectious disease • Pregnancy or breast feeding • QT > 470 msec on screening ECG • Patients with a history of Torsades de Pointes
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate if fixed starting doses of ICL670, dependent on transfusion history, and subsequent dose titration can provide clinically acceptable chelation among low and INT-1 risk MDS patients.;Secondary Objective: -Evaluate the safety and tolerability profile of ICL670 in low and INT-1 risk MDS patients treated for up to 52 weeks -Evaluate the change in LIC as assessed via non-invasive R2-MRI on EOS from baseline and the relationship between LIC and serum ferritin -Evaluate whether treatment with ICL670 reduces the blood transfusion requirement among MDS patients by inducing a hematologic response -Evaluate potential drug-drug interactions between ICL670 and other drugs used for supportive care of MDS patients -Evaluate Cardiac Iron Concentration via non-invasive T2*-MRI on baseline and EOS. -Evaluate the mean daily number of diarrhea episodes -Evaluate the mean duration of diarrhea episodes -Evaluate the incidence of either moderate or severe episodes;Primary end point(s): To demonstrate the efficacy of ICL670 in its favorable effect on iron load, the primary efficacy parameter serum ferritin will be assessed during the run-in period, every 4 weeks at regular study visits and at end of treatment. | — |
Countries
Germany
Outcome results
None listed