Repurposed Drugs to Improve Haematological Responses in Myelodysplastic Syndromes

NCT ID: NCT04997811

Last Updated: 2023-10-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-21

Study Completion Date

2025-06-30

Brief Summary

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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.

Detailed Description

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Conditions

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Myelodysplastic Syndromes (MDS)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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VBaP

Combination of sodium valproate, bezafibrate, medroxyprogesterone

Group Type EXPERIMENTAL

Sodium Valproate, Bezafibrate, Medroxyprogesterone

Intervention Type DRUG

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)

Danzol

Single agent

Group Type EXPERIMENTAL

Danazol

Intervention Type DRUG

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

Interventions

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Sodium Valproate, Bezafibrate, Medroxyprogesterone

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)

Intervention Type DRUG

Danazol

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Provision of written informed consent
2. Age ≥ 18 years and able to give informed consent
3. Diagnosis of Myelodysplastic Syndrome with an IPSS-R score of less than or equal to 3.51
4. Haematological parameters:

1. Mean haemoglobin \< 100 g/l over 16 weeks (pre transfusion) OR
2. Mean platelets \< 100 x 109/l over 16 weeks + evidence of bleeding (assessed using the ISTH Bleeding Assessment Tool) OR
3. Mean neutrophils \< 1.0 x 109/l over 16 weeks + history of infection (the requirement for antimicrobial therapy and hospital admissions associated with infection)
5. 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).
6. ECOG performance status 0-3
7. Expected survival \> 12months

Exclusion Criteria

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Blood Cancer UK

UNKNOWN

Sponsor Role collaborator

Dudley Group NHS Foundation Trust

OTHER

Sponsor Role collaborator

University of Birmingham

OTHER

Sponsor Role collaborator

University of Manchester

OTHER

Sponsor Role collaborator

King's College Hospital NHS Trust

OTHER

Sponsor Role collaborator

Prof. Janet Dunn

OTHER

Sponsor Role lead

Responsible Party

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Prof. Janet Dunn

Professor of Clinical Trials

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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Heartlands Hospital

Birmingham, Bordesley Green East, United Kingdom

Site Status RECRUITING

Royal Cornwall Hospital NHS Trust

Truro, Cornwall, United Kingdom

Site Status RECRUITING

University Hospitals Dorset NHS Foundation Trust

Poole, Dorset, United Kingdom

Site Status RECRUITING

Russells Hall Hospital

Dudley, England, United Kingdom

Site Status RECRUITING

University College London Hospitals NHS Foundation Trust

London, England, United Kingdom

Site Status RECRUITING

King's College Hospital NHS Foundation Trust

London, England, United Kingdom

Site Status RECRUITING

Broomfield Hospital

Chelmsford, Essex, United Kingdom

Site Status RECRUITING

Colchester General Hospital

Colchester, Essex, United Kingdom

Site Status RECRUITING

Basingstoke and North Hampshire Hospital,

Basingstoke, Hampshire, United Kingdom

Site Status RECRUITING

Royal Hampshire County Hospital, Hampshire Hospitals NHS Foundation Trust

Winchester, Hampshire, United Kingdom

Site Status RECRUITING

East Kent Hospitals University Foundation Trust

Canterbury, Kent, United Kingdom

Site Status RECRUITING

James Paget University Hospitals NHS Foundation Trust

Gorleston-on-Sea, Norfolk, United Kingdom

Site Status RECRUITING

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

Nottingham, Nottinghamshire, United Kingdom

Site Status RECRUITING

Grampian Health Board

Aberdeen, Scotland, United Kingdom

Site Status RECRUITING

Good Hope Hospital

Birmingham, Sutton Coldfield, United Kingdom

Site Status RECRUITING

Hull University Teaching Hospitals

Hull, , United Kingdom

Site Status RECRUITING

Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust

Leicester, , United Kingdom

Site Status RECRUITING

James Cook University Hospital, South Tees Hospitals NHS Foundation Trust

Middlesbrough, , United Kingdom

Site Status RECRUITING

Royal Gwent Hospital, Aneurin Bevan University Health Board

Newport, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Bethany Foster, BSc

Role: CONTACT

0044 24 76575675

Helen Higgins, MSc

Role: CONTACT

0044 24 76151178

Facility Contacts

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Research and Development Manager

Role: primary

Head of Research & Development

Role: primary

Head of Research

Role: primary

Research and Development Department

Role: primary

Contracts Manager

Role: primary

Research & Innovation Governance Manager

Role: primary

Research Development

Role: primary

Head of Research

Role: primary

Research Department

Role: primary

Research Department

Role: primary

R&I/CTU Manager

Role: primary

Research and Development Office

Role: primary

R&I Administrator

Role: primary

Research and Development

Role: primary

Research Department

Role: primary

R&D Manager

Role: primary

R&I Offices

Role: primary

Research Manager

Role: primary

R&D Assistant Director

Role: primary

Jeanette Wells

Role: backup

Related Links

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Other Identifiers

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2020-005446-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SOC.11/20-21

Identifier Type: -

Identifier Source: org_study_id

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