Iron overload in patients being treated for Myelodysplastic syndroms (MDS) by regular blood transfusions MedDRA version: 14.1 Level: LLT Classification code 10068361 Term: MDS System Organ Class: 100000004864 MedDRA version: 14.1 Level: LLT Classification code 10040310 Term: Serum iron increased System Organ Class: 100000004848
Conditions
Interventions
Trade Name: Exjade
Product Name: Deferasirox
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: Deferasirox
CAS Number: 201530
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • At least 18 years old. • Written informed consent. • MDS with: o Baseline haemoglobin concentration 300µg/l but 40 mls/min o ALT or AST =65 years) yes F.1.3.1 Number of subjects for this age range 29
Exclusion criteria
Exclusion criteria: • Active treatment for MDS, including erythropoetic stimulating agents (ESA), 5-azacitidine, antilymphocyte globulin and low dose chemotherapy such as cytarabine during the trial and within the last 8 weeks • Life expectancy of less than 1 year • Known HIV positive • Active infection • Use of prior investigational agents within 6 weeks • Pregnancy or lactation •Other severe, concurrent medical illness that may affect the patients participation in the study, or psychiatric disorders • Concurrent active or previous malignancy, within the last 3 years, – except controlled, localised prostate cancer on hormone therapy or basal cell carcinoma or cervical carcinoma in situ or completely resected colonic polyps carcinoma in situ • Ongoing inflammation as measured by CRP > 3 x ULN • Serum creatinine >1.2 x ULN and/or creatinine clearance 2.5 ULN • History of drug/alcohol abuse or non-compliance
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary aim of this study is to assess the activity of the study drug by measuring how long it takes for the levels of iron in the blood to rise to over 1500µg/l (a level associated with a poor prognosis and organ damage) when treated with Deferasirox. ; Secondary Objective: The secondary aims are to assess the proportion of patients who reach the the 1500µg/l during the 12 months of treatment, the Safety and tolerability of the drug in this population of patients, by collecting data on side effects, as well as measuring the proportion of patients maintaining a serum ferritin level in their blood of less than 1500 µg/l. We will also be measuring the cardiac and hepatic iron loading by MRI scan, in patients willing to undergo imaging, to see if the heart and liver stores of iron have increased during the study as wells as measuring the patients endocrine function to see if this has been altered during treatment. All patients will also be asked to provide blood samples for Biochemical iron parameter tests to look and different iron related proteins in the blood and how they change during treatment. We will be collecting data to measure the proportion of patient achieving a Haematological response, the time to this response and the duration of this respo ; Primary end point(s): The Primary outcome is Time to mean serum Ferritin > 1500 µg/l, as measured from the time of initiation using the mean serum Ferritin value of 2 consecutive measurements of Ferritin, where the first level is >1500 µg/l and CRP is 1500 µg/l, the first level is used and an event is assumed to have occurred. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Proportion of patients with mean serum Ferritin, of 2 consecutive measurements of Ferritin, >1500 µg/l within 12 months, where the first level is >1500 µg/l and CRP is < 3 times baseline measurement. - Safety and tolerability is defined in terms of the following events deemed to be related to Deferasirox and graded according to the CTCAE Criteria, version 4: a) Grade 3/4 non-haematological toxicity that does not resolve to = Grade 2 within 4 weeks of deferasirox withdrawal, b) unexpected Grade 3/4 non-haematological toxicity, c) =Grade 2 auditory or ocular abnormalities associated with chelation therapy. - Proportion of patients maintaining serum ferritin <1500 µg/l at 12 months - Cardiac and hepatic iron loading quantified by MRI R2 and T2* is defined as the mean change in iron concentration pre-treatment and at 12 months or when serum Ferritin levels exceed 2000 µg/l. This will be available for patients treated within a centre offering iron quantitation by MRI, or willing to travel. - Endocrine function is defined as the mean change in the following parameters pre-treatment and at 12 months; diabetes (HbA1c), thyroid (as measured by serum thyroid hormone concentration), sex hormones (measured by serum FSH, LH, testosterone) and adrenal (measured by cortisol). - Proportion of patients achieving hematologic response per IWG2006 criteria - Time to haematological response per IWG2006 criteria - Duration of haematological response per IWG2006 criteria - Biochemical iron parameters including transferrin saturation, hepcidin, non-transferrin bound iron and GDF15 as measure by the central laboratory at UCL. ;Timepoint(s) of evaluation of this end point: The safety outcome measures will be assessed using the safety analysis set. Toxicity will be assessed continuously throughout the study according to CTC vers | — |
Countries
United Kingdom
Contacts
Public ContactTrial Office
CRCTU, University of Birmingham
Outcome results
None listed