Myelodysplastic syndrome, transfusional iron overload MedDRA version: 20.0 Level: LLT Classification code 10019613 Term: Hemosiderosis System Organ Class: 100000004861 MedDRA version: 20.0 Level: LLT Classification code 10028534 Term: Myelodysplastic syndrome NOS System Organ Class: 100000004864
Conditions
Interventions
Trade Name: EXJADE
Product Name: deferasirox
Product Code: ICL670
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: DEFERASIR
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or female , =18 years of age • Weight between 35-135kg • Patients with with low or intermediate (int-1) risk MDS, as determined by IPSS score. This must be confirmed by a bone marrow examination within 6 months prior to study entry and must be hematologically stable. • Ferritin > 1000 mcg/L at screening • Serum ferritin will be measured at Screening Visit 1 and Screening Visit 2 (at least 14 days apart) and the mean value will be used for eligibility criteria. • History of transfusion of 15 to 75 PRBC units • Anticipated to be transfused with at least 8 units of PRBCs annually during the study Additional inclusion criteria as per full protocol may apply. 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 83 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 127
Exclusion criteria
Exclusion criteria: • More than 6 months of cumulative iron chelation therapy (such as daily deferasirox (Exjade) or deferiprone or 5x/week deferoxamine). - Intermittent deferoxamine doses in association with blood transfusions are not exclusionary regardless of duration of such treatment • More than 3 years since patient began receiving regular transfusions (2 units per 8 weeks or 4 units received in a 3 month period) • Creatinine Clearance 1.5 x ULN at screening - Serum creatinine will be measured at Screening Visit 1 and Screening Visit 2 (at least 14 days apart) and the mean value will be used for eligibility criteria. • Significant proteinuria as indicated by a urinary protein/creatinine ratio > 0.5 mg/mg in a non-first void urine sample at Visit 1 or Visit 2 (or alternatively in two of three samples obtained for screening) • ECOG performance status > 2 • Left ventricular ejection fraction 3.5 × ULN at screening • Total bilirubin >1.5 x ULN at screening • Diagnosis of liver cirrhosis (either established diagnosis or diagnosis by liver biopsy or central ultrasound reading). • Patients participating in another clinical trial other than an observational registry study • Patients with a history of another malignancy within the past five years, with the exception of basal skin carcinoma or cervical carcinoma in situ or completely resected colonic polyps carcinoma in situ. • History of non-compliance to medical regimens, or patients who are considered potentially unreliable and/or not cooperative • Presence of a surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of study drug • Pregnant, or breast-feeding patients, or patients of child-bearing potential not employing an effective method of birth control (see Women of child-bearing potential, below, for futher details regarding effective methods of birth control). • History of drug or alcohol abuse within the 12 months prior to enrollment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Baseline at day 1, bi-weekly during the first month, then every 4 weeks thereafter until end of treatment.;Main Objective: To evaluate deferasirox and placebo with regard to event-free survival (a composite primary endpoint including death and non-fatal events related to cardiac and liver function and transformation to AML) in low and int-1 risk MDS patients with transfusional iron overload.; Secondary Objective: To evlauate: • Haematologic improvement (HI) in terms of erythroid response • Overall survival •Change in endocrine function (thyroid and glycemic control) • Disease progression (which includes MDS progression and progression to AML) • Change in serum ferritin level • Change in cardiac function •Frequency of infections requiring intravenous antimicrobials • Safety, in particular to assess the levels of increased risk for pre-specified adverse events that would be clinically unacceptable in the context of the level of benefit that is likely to be provided by iron chelation using deferasirox in MDS patients with iron overload ; Primary end point(s): Composite primary endpoint (event-free survival) defined as time from date of randomization to either death or any of the following non-fatal events: 1. Echocardiographic evidence of worsening cardiac function 2. Hospitalization for congestive heart failure 3. Liver function impairment 4. Liver cirrhosis 5. Progression to Acute Myeloid Leukemmia (AML) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Main secondary endpoints include: • Proportion of patients with haematologic improvement in terms of erythroid response • Overall survival • Proportion of patients with hypothyroidism • Proportion of patients with worsening of glucose metabolism • Disease progression • Time to first occurrence of serum ferritin > 2 times the baseline value • Time to at least a 10% increase frome baseline in LVIDD • Time to at least a 10% increase frome baseline in LVISD • Infections Other secondary endpoints may apply as per protocol ; Timepoint(s) of evaluation of this end point: • Baseline at day 1, bi-weekly during the first month, then every 4 weeks thereafter until end of treatment (up to 5 yrs) • Baseline at day 1, bi-weekly during the first month, then every 4 weeks thereafter until EoT (up to 5 yrs) • annually • annually • baseline at day 1, bi-weekly during the 1st month, then every 4 weeks thereafter until EoT (up to 5 yrs) • baseline at day 1, bi-weekly during the 1st month, then every 4 weeks thereafter until EoT (up to 5 yrs) • baseline at day 1, bi-weekly during the 1st month, then every 4 weeks thereafter until EoT (up to 5 yrs) • baseline at day 1, bi-weekly during the 1st month, then every 4 weeks thereafter until EoT (up to 5 yrs) • baseline at day 1, bi-weekly during the 1st month, then every 4 weeks thereafter until EoT (up to 5 yrs) | — |
Countries
Australia, Belgium, Bulgaria, Canada, China, Denmark, Finland, Greece, Hong Kong, Italy, Malaysia, Mexico, Netherlands, New Zealand, Russian Federation, Switzerland, Thailand, United Kingdom
Contacts
Public ContactMedical Collaboration Centre
Novartis Pharmaceuticals UK Ltd
Outcome results
None listed