1. SUB-TYPE OF MDS: All subtypes of MDS
2. SEVERITY OF MDS:  Lower-risk MDS
3. NAME OF DRUG: 
4. Aims and benefits: REPAIR-MDS seeks to repurpose existing drugs in order to dramatically improve the outlook, health and quality of life of people with MDS. The trial treatments aim to improve the production of healthy functioning blood and immune cells that will fight against infections and boost the immune system's action against the MDS clone.
   REPAIR-MDS design is a is a multicentre open label phase 2 randomised controlled trial which will compare VBaP (sodium valproate, bezafibrate, medroxyprogesterone) with danazol in patients who have received either Erythropoiesis Stimulating Agents (ESAs) and lost response, not responded to ESAs or are deemed unlikely to respond to ESAs.
5. Primary outcome: Haematological improvement (HI) in each arm and in the trial overall, with 25% or more of the participants having HI in each arm and overall. [ Time Frame: 12 months ]
6. Secondary outcome:  Reduced burden of red cell and/or platelet transfusion in each arm and in the trial overall, as per the IWG 2018 response criteria. [ Time Frame: 12 months ] Changes in transfusion requirements will be assessed in each participant by comparison with their individual 16-week lead-in baseline as determined by the IWG 2018 haematology response criteria in patients with MDS.
   • Duration of haematological response [ Time Frame: 12 months ]
   • Clinically meaningful haematological responses that persist for 16 weeks or longer.
   • Reported improved Health Related Quality of Life scores in each arm and in the trial overall. [ Time Frame: 12 months ]
   • The four Health Related Quality of Life questions measure
     1. 1 - self-perceived health (excellent, very good, good, fair, or poor)
     2. 2 - number of days out of the past 30 that physical health was not good
     3. 3 - number of days out of the past 30 that mental health was not good,
     4. 4 - number of days out of the past 30 that usual activities were limited by poor physical or mental health of life scores will be evaluated using established protocols.
   • Overall survival

1. Basic inclusion criteria: (main ones)
   • Haematological parameters: Mean haemoglobin < 100 g/l over 16 weeks (pre transfusion) OR
   • Mean platelets < 100 x 109/l over 16 weeks + evidence of bleeding (assessed using the ISTH Bleeding Assessment Tool) OR
   • Mean neutrophils < 1.0 x 109/l over 16 weeks + history of infection (the requirement for antimicrobial therapy and hospital admissions associated with infection)
   • No response to Erythroid Stimulating Agents (ESAs) OR Have Ceased to respond to ESAs OR are predicated not to respond to ESAs
2. Basic exclusion criteria: (main ones)
   • History of having received ESAs and/or G-CSF in the past 16 weeks
   • Currently receiving statin medication for Secondary Prophylaxis of Cardiovascular Disease or Cerebrovascular disease (Please note patients receiving statin medication for Primary Prophylaxis of Cardiovascular Disease - i.e. the patient has no prior history of Ischaemic Heart Disease nor Cerebrovascular Disease - can still be entered, please see section 1.4 Statin use)
   • Currently receiving fibrate medications
   • Currently receiving sodium valproate, carbamazepine or phenytoin for treatment of epilepsy
   • Prior cytotoxic chemotherapy for AML/MDS
   • Concurrent active malignancy requiring treatment
   • History of any Androgen Dependent Tumour (patients with Prostate Cancer are Excluded when a biopsy proven diagnosis of Prostate Cancer has been made OR their PSA is known to be elevated OR they are on active treatment for Prostate Cancer, including hormonal therapy).
3. Trial sites/locations and name of physician in charge of trial (none are currently recruiting)

   • Russells Hall Hospital, Dudley, West Midlands, DY1 2HQ - Dr Steve Jenkins

   • University Hospital College,  235 Euston Rd, London NW1 2BU - Dr Elspeth Payne

   • Aberdeen Royal Infirmary, Foresterhill Health Campus, Foresterhill Rd, Aberdeen AB25 2ZN - Dr Dominic Culligan

   • Kings College Hospital, Denmark Hill, London SE5 9RS - Dr Austin Kulasekararaj

   • East Kent and Canterbury Hospital, Ethelbert Rd, Canterbury CT1 3NG - Dr Sreetharan Munisamy 

   • Castle Hill Hospital Hull, Castle Rd, Cottingham HU16 5JQ - Dr Simone Green

   • Royal Devon and Exeter, Barrack Rd, Exeter EX2 5DW - Dr Anthony Todd

   • University Hospitals, Birmingham, Queen Elizabeth Hospital Mindelsohn Way, Birmingham, B15 2GW - Dr Manoj Raghavan

   • Aneurin Bevan University Health Board, 1, Llanarth House, Newbridge Gateway, Newbridge, Newport NP11 5GH - Dr Ali Mahdi

   • Royal Hallamshire Hospital, Sheffield Teaching Hospital, Glossop Rd, Broomhall, Sheffield S10 2JF - Dr Harpreet Kaur

   • Royal Cornwall Hospital, Royal Cornwall Hospitals NHS Trust, Treliske, Truro TR1 3LJ - Dr Ruth Witherall

   • The Royal Bournemouth Hospital, Castle Lane East, Bournemouth, BH7 7DW - Dr Mohamed Hamid

   • The James Cook University Hospital, South Tees Hospital NHS Trust, Marton Rd, Middlesbrough TS4 3BW - Dr Dianne Plews

   • Colchester General Hospital, Turner Rd, Colchester CO4 5JL -  Dr Mike Hamblin

   • Nottingham University Hospital, Derby Road , Nottingham, Nottinghamshire, NG7 2UH - Dr Jennifer Byrne

   • Broomfield Hospital Mid and South Essex, University Hospitals Group Court Rd, Broomfield, Chelmsford CM1 7ET

   • HOPE Cancer Trials Centre, Leicester Royal Infirmary, Infirmary Square, Leicester LE1 5WW

   • Mid and South Essex University Hospitals Group, Prittlewell Chase, Westcliff-on-Sea, Southend-on-Sea, Westcliff-on-Sea SS0 0RY

For full information see ClinicalTrials .gov website . If you think this information is relevant to you, please discuss it with your own physician.