NCT04997811

Brief 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. 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
120

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Dec 2021

Typical duration for phase_2

Geographic Reach
1 country

19 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 23, 2021

Completed
18 days until next milestone

First Posted

Study publicly available on registry

August 10, 2021

Completed
4 months until next milestone

Study Start

First participant enrolled

December 21, 2021

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 31, 2025

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2025

Completed
Last Updated

October 3, 2023

Status Verified

October 1, 2023

Enrollment Period

3.1 years

First QC Date

July 23, 2021

Last Update Submit

October 2, 2023

Conditions

Outcome Measures

Primary Outcomes (1)

  • 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.

    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.

    12 months

  • Duration of haematological response

    12 months

  • Reported improved Health Related Quality of Life scores in each arm and in the trial overall.

    12 months

  • Overall survival

    Through study completion, an average of 1 year

Study Arms (2)

VBaP

EXPERIMENTAL

Combination of sodium valproate, bezafibrate, medroxyprogesterone

Drug: Sodium Valproate, Bezafibrate, Medroxyprogesterone

Danzol

EXPERIMENTAL

Single agent

Drug: Danazol

Interventions

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)

VBaP

Danazol 1 x 200mg capsules tds, (starting 1 x 200mg od)

Danzol

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • 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

You may not qualify if:

  • \. 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (19)

Heartlands Hospital

Birmingham, Bordesley Green East, B9 5SS, United Kingdom

RECRUITING

Royal Cornwall Hospital NHS Trust

Truro, Cornwall, TR1 3LJ, United Kingdom

RECRUITING

University Hospitals Dorset NHS Foundation Trust

Poole, Dorset, BH15 2JB, United Kingdom

RECRUITING

Russells Hall Hospital

Dudley, England, DY1 2HQ, United Kingdom

RECRUITING

University College London Hospitals NHS Foundation Trust

London, England, NW1 2PG, United Kingdom

RECRUITING

King's College Hospital NHS Foundation Trust

London, England, SE5 9RS, United Kingdom

RECRUITING

Broomfield Hospital

Chelmsford, Essex, CM1 7ET, United Kingdom

RECRUITING

Colchester General Hospital

Colchester, Essex, CO4 5JL, United Kingdom

RECRUITING

Basingstoke and North Hampshire Hospital,

Basingstoke, Hampshire, RG24 9NA, United Kingdom

RECRUITING

Royal Hampshire County Hospital, Hampshire Hospitals NHS Foundation Trust

Winchester, Hampshire, SO22 5DG, United Kingdom

RECRUITING

East Kent Hospitals University Foundation Trust

Canterbury, Kent, CT1 3NG, United Kingdom

RECRUITING

James Paget University Hospitals NHS Foundation Trust

Gorleston-on-Sea, Norfolk, NR31 6LA, United Kingdom

RECRUITING

Nottingham City Hospital, Nottingham University Hospitals NHS Trust, Hucknall Road

Nottingham, Nottinghamshire, NG5 1PB, United Kingdom

RECRUITING

Grampian Health Board

Aberdeen, Scotland, AB15 6RE, United Kingdom

RECRUITING

Good Hope Hospital

Birmingham, Sutton Coldfield, B75 7RR, United Kingdom

RECRUITING

Hull University Teaching Hospitals

Hull, HU3 2JZ, United Kingdom

RECRUITING

Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust

Leicester, LE1 5WW, United Kingdom

RECRUITING

James Cook University Hospital, South Tees Hospitals NHS Foundation Trust

Middlesbrough, TS4 3BW, United Kingdom

RECRUITING

Royal Gwent Hospital, Aneurin Bevan University Health Board

Newport, NP18 3XQ, United Kingdom

RECRUITING

Related Links

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Valproic AcidBezafibrateMedroxyprogesteroneDanazol

Condition Hierarchy (Ancestors)

Bone Marrow DiseasesHematologic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Pentanoic AcidsValeratesAcids, AcyclicCarboxylic AcidsOrganic ChemicalsFatty Acids, VolatileFatty AcidsLipidsBenzamidesAmidesFibric AcidsIsobutyratesButyratesBenzoatesAcids, CarbocyclicChlorobenzoatesPhenyl EthersEthersBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsPhenolsHydroxyprogesteronesProgesteronePregnenedionesPregnenesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsPregnadienes

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Professor of Clinical Trials

Study Record Dates

First Submitted

July 23, 2021

First Posted

August 10, 2021

Study Start

December 21, 2021

Primary Completion

January 31, 2025

Study Completion

June 30, 2025

Last Updated

October 3, 2023

Record last verified: 2023-10

Locations