Myelodysplastic Syndromes (MDS)Phase 2REPAIR-MDSNCT04997811
Repurposed Drugs to Improve Haematological Responses in Myelodysplastic Syndromes
A Phase 2 study testing Sodium Valproate, Bezafibrate, Medroxyprogesterone and Danazol in people with Myelodysplastic Syndromes (MDS), run by Prof. Janet Dunn at 19 sites in United Kingdom.
Trial summary
Over 7,000 people in the UK are living with Myelodysplastic Syndromes (MDS). Approximately 1,600 of these individuals (23%) die each year from their disease. MDS affects the production of blood cells by the bone marrow, causing chronic fatigue, bleeding, and recurrent infections. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes (MDS)
- What is being tested?
- Sodium Valproate, Bezafibrate, Medroxyprogesterone and Danazol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 19 sitesUnited Kingdom
- Study dates
- 21 Dec 2021to 30 Jun 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of written informed consent
- Age ≥ 18 years and able to give informed consent
- Diagnosis of Myelodysplastic Syndrome with an IPSS-R score of less than or equal to 3.51
- 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
Show all 10Show fewer
- 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 by current UK guidelines2,3 (NB Patients with thrombocytopenia and/or neutropenia, without anaemia, are eligible as they are predicated not to respond to ESAs).
- ECOG performance status 0-3
- Expected survival > 12months
Who cannot join
- Abnormal liver function (if patient has Gilbert's syndrome, then abnormal direct Bilirubin is an exclusion) 2. Cockcroft Gault CrCl < 20ml/min 3. Current systemic treatment for low risk MDS 4. History of Allogeneic Bone Marrow Transplant 5. History of having received ESAs and/or G-CSF in the past 16 weeks 6. Currently receiving statin medication for Secondary Prophylaxis of Cardiovascular Disease, Cerebrovascular Disease or Peripheral Vascular 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) 7. Currently receiving fibrate medications 8. Currently receiving sodium valproate, carbamazepine or phenytoin for treatment of epilepsy 9. Prior cytotoxic chemotherapy or hypomethylating agents for AML/MDS (eg Azacitidine) 10. Concurrent active malignancy requiring treatment 11. 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).
- 12. Currently receiving Vitamin K-Antagonist Anticoagulation (though patients receiving DOACs (direct oral anticoagulants) can be included) 13. History of Venous Thrombo-Embolism (VTE) 14. Cardiac Failure NYHA Class III or IV 15. Women of childbearing potential, pregnant or lactating 16. The physician or patient consider VBaP or danazol to be inappropriate for the patient 17. Known HIV 18. Abnormally high CK level 19. Presence of isolated del 5q 20. Acute Porphyria 21. Contraindications to any of the trial medications or known hypersensitivity to any of the investigational products (see Appendix C for contraindications) 22. Previous randomisation in the REPAIR-MDS trial 23. Participation in a clinical trial of an investigational medicinal product in the last 16 weeks
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
United Kingdom19 sites, 19 recruiting
- Recruiting
Grampian Health Board
Aberdeen, Scotland, AB15 6RE
Research and Development, gram.randdpermissions@nhs.scot;
Dr Dominic Culligan
- Recruiting
Basingstoke and North Hampshire Hospital,
Basingstoke, Hampshire, RG24 9NA
Research Department, research.team@hhft.nhs.uk;
Dr Noel Ryman
- Recruiting
Heartlands Hospital
Birmingham, Bordesley Green East, B9 5SS
Research and Development Manager, R&D@uhb.nhs.uk;
Dr Manoj Raghavan
- Recruiting
Good Hope Hospital
Birmingham, Sutton Coldfield, B75 7RR
Research Department, clinicalhaem@trials.bham.ac.uk;
Dr Manoj Raghavan
- Recruiting
East Kent Hospitals University Foundation Trust
Canterbury, Kent, CT1 3NG
R&I/CTU Manager, ekhuft.researchandinnovation@nhs.net
Dr Sreetharan Munisamy
- Recruiting
Broomfield Hospital
Chelmsford, Essex, CM1 7ET
Research Development, mse.research.meht@nhs.net
Dr Pavel Kotoucek
- Recruiting
Colchester General Hospital
Colchester, Essex, CO4 5JL
Head of Research, R&D@esneft.nhs.uk
Dr Mike Hamblin
- Recruiting
Russells Hall Hospital
Dudley, England, DY1 2HQ
Research and Development Department, dgft.research.rhh@nhs.net
Dr Stephen Jenkins
- Recruiting
James Paget University Hospitals NHS Foundation Trust
Gorleston-on-Sea, Norfolk, NR31 6LA
Research and Development Office, rd.office@jpaget.nhs.uk
Dr Thomas Mckerrell
- Recruiting
Hull University Teaching Hospitals
Hull, HU3 2JZ
R&D Manager, hyp-tr.newstudies@nhs.net
Dr Simone Green
- Recruiting
Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust
Leicester, LE1 5WW
R&I Offices, RIAdmin@uhl-tr.nhs.uk
Dr Katherine Hodgson
- Recruiting
University College London Hospitals NHS Foundation Trust
London, England, NW1 2PG
Contracts Manager, uclh.rand@nhs.net
Dr Elspeth Payne
- Recruiting
King's College Hospital NHS Foundation Trust
London, England, SE5 9RS
Research & Innovation Governance Manager, kch-tr.research@nhs.net
Dr Austin Kulasekararaj
- Recruiting
James Cook University Hospital, South Tees Hospitals NHS Foundation Trust
Middlesbrough, TS4 3BW
Research Manager, stees.dtvra@nhs.net
Dr Matthew Horran
- Recruiting
Royal Gwent Hospital, Aneurin Bevan University Health Board
Newport, NP18 3XQ
R&D Assistant Director, rand.abb@wales.nhs.uk
Jeanette Wells, jeanette.wells@wales.nhs.uk
- Recruiting
Nottingham City Hospital, Nottingham University Hospitals NHS Trust, Hucknall Road
Nottingham, Nottinghamshire, NG5 1PB
R&I Administrator, R&I@NUH.nhs.uk
Dr Yadanar Lwin
- Recruiting
University Hospitals Dorset NHS Foundation Trust
Poole, Dorset, BH15 2JB
Head of Research, researchoffice@uhd.nhs.uk
Dr Catherine Hockings
- Recruiting
Royal Cornwall Hospital NHS Trust
Truro, Cornwall, TR1 3LJ
Head of Research & Development, rch-tr.cornwallresearch@nhs.net
Dr Ruth Witherall
- Recruiting
Royal Hampshire County Hospital, Hampshire Hospitals NHS Foundation Trust
Winchester, Hampshire, SO22 5DG
Research Department, research.team@hhft.nhs.uk;
Dr Jennifer Arnold
About this study
Official title: Evaluation of Haematological Improvement in Patients With Low-risk MDS by Comparing VBaP With Danazol in Patients Who Have Either Received Erythropoiesis Stimulating Agents (ESA) and Lost Response, Not Responded to ESA or Are Deemed Unlikely to Respond to ESA
Over 7,000 people in the UK are living with Myelodysplastic Syndromes (MDS). Approximately 1,600 of these individuals (23%) die each year from their disease. MDS affects the production of blood cells by the bone marrow, causing chronic fatigue, bleeding, and recurrent infections. Many patients die because their disease transforms into acute myeloid leukaemia (AML) an even more aggressive blood cancer. The general outlook for AML is poor, but when AML arises from MDS it is worse.
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.
- Conditions
- Myelodysplastic Syndromes (MDS)
- Being tested
- Sodium Valproate, Bezafibrate, Medroxyprogesterone, Danazol
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium Valproate, Bezafibrate, MedroxyprogesteroneDrug
Sodium valproate tablet 1 x 500mg bd, (starting 1 x 200mg bd) Bezafibrate standard release tablet 2 x 200mg tds, (starting 1 x 200mg tds) Medroxyprogesterone acetate tablet 1 x 400mg bd (starting 1 x 400mg od)
DanazolDrug
Danazol 1 x 200mg capsules tds, (starting 1 x 200mg od)
| Study group | Role | What they receive |
|---|---|---|
| VBaP | Experimental | Combination of sodium valproate, bezafibrate, medroxyprogesterone Receives: Drug: Sodium Valproate, Bezafibrate, Medroxyprogesterone |
| Danzol | Experimental | Single agent Receives: Drug: Danazol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
HI will be assessed in each participant by comparing post randomisation FBC parameters (Haemoglobin, platelet and neutrophil counts) and transfusion requirements, with their individual baseline as determined by the IWG 2018 haematology response criteria in patients with MDS.
Measured: 12 months
Secondary outcomes (4)
Reduced burden of red cell and/or platelet transfusion in each arm and in the trial overall, as per the IWG 2018 response criteria.
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.
Measured: 12 months
Duration of haematological response
Clinically meaningful haematological responses that persist for 16 weeks or longer.
Measured: 12 months
Reported improved Health Related Quality of Life scores in each arm and in the trial overall.
The four Health Related Quality of Life questions measure 1) self-perceived health (excellent, very good, good, fair, or poor), (2) number of days out of the past 30 that physical health was not good, (3) number of days out of the past 30 that mental health was not good, and (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.
Measured: 12 months
Overall survival
Overall survival at close of trial will be reported separately for each trial arm
Measured: Through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2021
- Study start21 Dec 2021
- Primary completion31 Jan 2025 (estimated)
- Study completion30 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic Syndromes (MDS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Prof. Janet Dunn
- Sponsor type
- University, hospital or other
- Collaborators
- Blood Cancer UK, Dudley Group NHS Foundation Trust, University of Birmingham, University of Manchester, King's College Hospital NHS Trust
- Responsible party
- Sponsor-investigator, Prof. Janet Dunn, University of Warwick
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04997811
- Sponsor's protocol ID
- SOC.11/20-21
- Other IDs
- 2020-005446-42
- Acronym
- REPAIR-MDS
- Status last verified
- Oct 2023
- First submitted
- 23 Jul 2021
- Last updated
- 3 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Haematological Improvement in Patients With Low-risk MDS by Comparing VBaP With Danazol in Patients Who Have Either Received Erythropoiesis Stimulating Agents (ESA) and Lost Response, Not Responded to ESA or Are Deemed Unlikely to Respond to ESA
- ClinicalTrials.gov ID
- NCT04997811
- Acronym / sponsor ID
- REPAIR-MDS / SOC.11/20-21
- Conditions
- Myelodysplastic Syndromes (MDS)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Prof. Janet DunnUniversity, hospital or other
- Collaborators
- Blood Cancer UK, Dudley Group NHS Foundation Trust, University of Birmingham, University of Manchester, King's College Hospital NHS Trust
- Study start
- 21 Dec 2021 (actual)
- Primary completion
- 31 Jan 2025 (estimated)
- Study completion
- 30 Jun 2025 (estimated)
- First posted
- 10 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Over 7,000 people in the UK are living with Myelodysplastic Syndromes (MDS). Approximately 1,600 of these individuals (23%) die each year from their disease. MDS affects the production of blood cells by the bone marrow, causing chronic fatigue, bleeding, and recurrent infections. Many patients die because their disease transforms into acute myeloid leukaemia (AML) an even more aggressive blood cancer. The general outlook for AML is poor, but when AML arises from MDS it is worse.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| VBaP | Experimental | Drug: Sodium Valproate, Bezafibrate, MedroxyprogesteroneCombination of sodium valproate, bezafibrate, medroxyprogesterone |
| Danzol | Experimental | Drug: DanazolSingle agent |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Provision of written informed consent
- Age ≥ 18 years and able to give informed consent
- Diagnosis of Myelodysplastic Syndrome with an IPSS-R score of less than or equal to 3.51
- Haematological parameters:
- No response to Erythroid Stimulating Agents (ESAs) OR Have Ceased to respond to ESAs OR are predicated not to respond to ESAs by current UK guidelines2,3 (NB Patients with thrombocytopenia and/or neutropenia, without anaemia, are eligible as they are predicated not to respond to ESAs).
Key exclusion criteria (2 listed)
- Abnormal liver function (if patient has Gilbert's syndrome, then abnormal direct Bilirubin is an exclusion) 2. Cockcroft Gault CrCl < 20ml/min 3. Current systemic treatment for low risk MDS 4. History of Allogeneic Bone Marrow Transplant 5. History of having received ESAs and/or G-CSF in the past 16 weeks 6. Currently receiving statin medication for Secondary Prophylaxis of Cardiovascular Disease, Cerebrovascular Disease or Peripheral Vascular 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) 7. Currently receiving fibrate medications 8. Currently receiving sodium valproate, carbamazepine or phenytoin for treatment of epilepsy 9. Prior cytotoxic chemotherapy or hypomethylating agents for AML/MDS (eg Azacitidine) 10. Concurrent active malignancy requiring treatment 11. 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).
- 12. Currently receiving Vitamin K-Antagonist Anticoagulation (though patients receiving DOACs (direct oral anticoagulants) can be included) 13. History of Venous Thrombo-Embolism (VTE) 14. Cardiac Failure NYHA Class III or IV 15. Women of childbearing potential, pregnant or lactating 16. The physician or patient consider VBaP or danazol to be inappropriate for the patient 17. Known HIV 18. Abnormally high CK level 19. Presence of isolated del 5q 20. Acute Porphyria 21. Contraindications to any of the trial medications or known hypersensitivity to any of the investigational products (see Appendix C for contraindications) 22. Previous randomisation in the REPAIR-MDS trial 23. Participation in a clinical trial of an investigational medicinal product in the last 16 weeks
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sodium Valproate, Bezafibrate, MedroxyprogesteroneSodium valproate tablet 1 x 500mg bd, (starting 1 x 200mg bd) Bezafibrate standard release tablet 2 x 200mg tds, (starting 1 x 200mg tds) Medroxyprogesterone acetate tablet 1 x 400mg bd (starting 1 x 400mg od) | Drug | VBaP |
| DanazolDanazol 1 x 200mg capsules tds, (starting 1 x 200mg od) | Drug | Danzol |
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
HI will be assessed in each participant by comparing post randomisation FBC parameters (Haemoglobin, platelet and neutrophil counts) and transfusion requirements, with their individual baseline as determined by the IWG 2018 haematology response criteria in patients with MDS.
4 secondary outcomes
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
Duration of haematological response
Time frame: 12 months
Reported improved Health Related Quality of Life scores in each arm and in the trial overall.
Time frame: 12 months
Overall survival
Time frame: Through study completion, an average of 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2023.
- REPAIR-MDS Trial WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
19 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sodium Valproate, Bezafibrate, Medroxyprogesterone and Danazol in people with Myelodysplastic Syndromes (MDS), run by Prof. Janet Dunn at 19 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Bethany Foster, BSc (0044 24 76575675, RepairMDS@warwick.ac.uk;), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2023.