• Change in exclusion criteria from >40ml/min creatinine clearance to >60ml/min creatinine clearance

• Addition of 2 secondary endpoints: (time to Haematological response and duration of response) • Reduction of Iron parameter sampling from 8 to 4 time points • Clarifications of dose modifications and discontinuation • Minor typing errors

• The addition of four sites: - University Hospital Southampton NHS Foundation Trust - University Hospital of Leicester NHS Trust - East Cheshire NHS Trust - Sherwood Forest NHS Foundation Trust

• The addition of two sites: The Royal Wolverhampton Hospitals NHS Trust Epsom and St Helier University Hospitals NHS Trust • Change of Trust name of Oxford Radcliff Hospitals NHS Trust to the Oxford University Hospitals NHS Trust.

Addition of three sites: • Northampton General Hospital NHS Trust • North West London Hospitals NHS Trust • North Bristol NHS Trust

• Change of Eligibility criteria - inclusion criteria updated to prevent patients entering the De-Iron study with platelets <30 x109/L and/or Neutrophils ≤0.5 x109/L • Addition of Trial Management staff and contact numbers • Clarification of MRI endpoint analysis • Correction of the schedule of events • Advice for missed doses and clarification of patient follow up and treatment discontinuation • Change to the IMP Label wording • Updates to Patient Information Sheet/Informed Consent Form - correction of the version of the Patient Information Sheet referenced in the Informed Consent Form, addition to clarify that patients may have to have a bone marrow biopsy, if they had not had one in the 6 months prior to entering the trial, and further information about the procedure

• Addition of 1 site - East Sussex Healthcare NHS Trust

• Addition of 1 site: - Royal Cornwall Hospitals NHS Trust

• Update to the Reference Safety Information (RSI) to reflect new information provided in the SPC (aggravated anaemia added as a new expected side effect) • Update to the Patient Information Sheet/Informed Consent Form to reflect the above change

• Modification of serum ferritin inclusion criteria to extend range from <1000μg/l to <1200μg/l • Minor typing errors • Changes to trials office contact details

• Addition of 1 site - Shrewsbury and Telford Hospitals NHS Trust

• Reordering of secondary endpoints • Changes to the definition of transfusion dependence - patients now able to start screening as soon as they start transfusions, rather than waiting 12 weeks before starting screening • Update to the schedule of assessments for clarity • Rewording of dose escalation for clarity • Updates and rewording of dose modification regarding Steven Johnsons Syndrome and pancreatitis • Update to the Patient Information Sheet to include Steven Johnsons Syndrome as a potential adverse event of unknown frequency and has added pancreatitis as a potential complication of gallstones that can develop from Deferasirox treatment

Update to the Reference Safety Information (RSI) to include Stevens-Johnson Syndrome and Pancreatitis added as new expected side effects of unknown frequency

• Addition of 1 site: - Taunton & Somerset NHS Foundation Trust

• Change of Principal Investigator at St James’ Hospital, Leeds

• Addition of 1 site: - South Tees Hospitals NHS Foundation Trust

• An extension of the recruitment period due to poor recruitment • A reduction in the recruitment target due to poor recruitment • Changes in the statistical considerations due to the updated recruitment target • An update of the eligibility criteria to include patients receiving erythropoietin • Changes in exclusion criteria to reduce use of prior investigational agents from 6 to 4 weeks, and clarification of active infection to ≥ grade 3 according to CTCAE v4 • Clarification of outcome measures to ensure appropriate statistical analysis • Clarifications to the trial assessments schedule to remove some inconsistencies observed by sites • Clarifications to the dose escalation section to include CRP <3 x ULN and EGFR ≥60 ml/min and change of serum ferritin tfrom 1500μg//L to 1350μg//L • Update to the dose modification section to include changes in the Deferasirox SPC • Clarifications to the discontinuation and follow-up procedures • Changes to adverse event reporting to exclude reporting of abnormal laboratory findings unless the abnormal laboratory finding results in early discontinuation, requires drug modification or interruption, requires therapeutic intervention or is of significant clinical importance • Inclusion of travel expenses to patients • Update to the Patient Information Sheet/Informed Consent Form to include updated information on dose modifications, travel expenses, Deferasirox information and side effects and to include the update that samples are not sent to Kings College, London. • Update to the GP letter to reflect updates to trial objectives, prescription of medication affecting hepatic and/or renal function or known to trigger skin reactions and care of patients who develop diarrhoea or vomiting. • Updates to the patient diary

• Change of Principal Investigator at Royal Cornwall Hospitals NHS Trust

• Update to the Reference Safety Information (RSI) to reflect new information provided in the SPC in the reporting year: - minor changes to the wording of the summary of the safety profile including the description of reduced creatinine cases in patients with beta thalassemia and iron overload - small changes to the terminology in the list of adverse reactions - Toxic Epidermal Necrolysis (TEN) has been added as a “not known” frequency side effect under Skin and subcutaneous tissue disorders - Acute pancreatitis has been added as a “not known” frequency side effect within gastrointestinal disorders - An additional paragraph added concerning creatinine clearance cases as identified in a retrospective meta-analysis

• Change of Principal Investigator at Conquest Hospital, East Sussex