Repurposed Drugs to Improve Haematological Responses in Myelodysplastic Syndromes (REPAIR-MDS)

October 2, 2023 updated by: Prof. Janet Dunn

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United Kingdom
      • Hull, United Kingdom, HU3 2JZ
        • Recruiting
        • Hull University Teaching Hospitals
        • Contact:
        • Principal Investigator:
          • Dr Simone Green
      • Leicester, United Kingdom, LE1 5WW
        • Recruiting
        • Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust
        • Contact:
        • Principal Investigator:
          • Dr Katherine Hodgson
      • Middlesbrough, United Kingdom, TS4 3BW
        • Recruiting
        • James Cook University Hospital, South Tees Hospitals NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Dr Matthew Horran
      • Newport, United Kingdom, NP18 3XQ
    • Bordesley Green East
      • Birmingham, Bordesley Green East, United Kingdom, B9 5SS
        • Recruiting
        • Heartlands Hospital
        • Contact:
        • Principal Investigator:
          • Dr Manoj Raghavan
    • Cornwall
      • Truro, Cornwall, United Kingdom, TR1 3LJ
        • Recruiting
        • Royal Cornwall Hospital NHS Trust
        • Contact:
        • Principal Investigator:
          • Dr Ruth Witherall
    • Dorset
      • Poole, Dorset, United Kingdom, BH15 2JB
        • Recruiting
        • University Hospitals Dorset NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Dr Catherine Hockings
        • Sub-Investigator:
          • Dr Mohamed Ifraz Hamid
        • Sub-Investigator:
          • Dr Helen Mccarthy
    • England
      • Dudley, England, United Kingdom, DY1 2HQ
        • Recruiting
        • Russells Hall Hospital
        • Contact:
        • Principal Investigator:
          • Dr Stephen Jenkins
        • Sub-Investigator:
          • Dr Jeff Neilson
        • Sub-Investigator:
          • Dr Shereef Elmoanly
        • Sub-Investigator:
          • Dr Ovini Gamage
      • London, England, United Kingdom, SE5 9RS
        • Recruiting
        • King's College Hospital NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Dr Austin Kulasekararaj
        • Sub-Investigator:
          • Dr Pramila Krishnamurthy
        • Sub-Investigator:
          • Dr Victoria Potter
      • London, England, United Kingdom, NW1 2PG
        • Recruiting
        • University College London Hospitals Nhs Foundation Trust
        • Contact:
        • Principal Investigator:
          • Dr Elspeth Payne
    • Essex
      • Chelmsford, Essex, United Kingdom, CM1 7ET
        • Recruiting
        • Broomfield Hospital
        • Principal Investigator:
          • Dr Pavel Kotoucek
        • Contact:
      • Colchester, Essex, United Kingdom, CO4 5JL
        • Recruiting
        • Colchester General Hospital
        • Contact:
        • Principal Investigator:
          • Dr Mike Hamblin
        • Sub-Investigator:
          • Dr Gavin Campbell
        • Sub-Investigator:
          • Dr Mahalakshmi Mohan
        • Sub-Investigator:
          • Dr Joseph Padayatty
        • Sub-Investigator:
          • Dr Khalid Saja
        • Sub-Investigator:
          • Dr Francis Anyanwu
    • Hampshire
      • Basingstoke, Hampshire, United Kingdom, RG24 9NA
        • Recruiting
        • Basingstoke and North Hampshire Hospital,
        • Contact:
        • Principal Investigator:
          • Dr Noel Ryman
        • Sub-Investigator:
          • Dr Katherine Smith
        • Sub-Investigator:
          • Dr Hussan Janan
        • Sub-Investigator:
          • Dr Henna Wong
        • Sub-Investigator:
          • Dr Kanchana De Abrew
      • Winchester, Hampshire, United Kingdom, SO22 5DG
        • Recruiting
        • Royal Hampshire County Hospital, Hampshire Hospitals NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Dr Jennifer Arnold
        • Sub-Investigator:
          • Dr Marianna Koperdanova
        • Sub-Investigator:
          • Dr Katharine Lowndes
    • Kent
      • Canterbury, Kent, United Kingdom, CT1 3NG
        • Recruiting
        • East Kent Hospitals University Foundation Trust
        • Contact:
        • Principal Investigator:
          • Dr Sreetharan Munisamy
        • Sub-Investigator:
          • Dr Iresha Dharmasena
        • Sub-Investigator:
          • Dr Caroline Grist
        • Sub-Investigator:
          • Dr Jindriska Lindsay
        • Sub-Investigator:
          • Dr Jayne Osborne
        • Sub-Investigator:
          • Dr Sharath Dr Sharath
        • Sub-Investigator:
          • Dr Samih Salih
        • Sub-Investigator:
          • Dr Moya Young
    • Norfolk
      • Gorleston-on-Sea, Norfolk, United Kingdom, NR31 6LA
        • Recruiting
        • James Paget University Hospitals NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Dr Thomas Mckerrell
    • Nottinghamshire
      • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
        • Recruiting
        • Nottingham City Hospital, Nottingham University Hospitals NHS Trust, Hucknall Road
        • Contact:
        • Principal Investigator:
          • Dr Yadanar Lwin
        • Sub-Investigator:
          • Dr Tom Taylor
        • Sub-Investigator:
          • Dr Gerardo Errico
        • Sub-Investigator:
          • Dr Malik Saeed
        • Sub-Investigator:
          • Dr Jennifer Byrne
    • Scotland
      • Aberdeen, Scotland, United Kingdom, AB15 6RE
        • Recruiting
        • Grampian Health Board
        • Contact:
        • Principal Investigator:
          • Dr Dominic Culligan
        • Sub-Investigator:
          • Mrs Mariella Lamacchia
        • Sub-Investigator:
          • Dr Stephanie Bruce
        • Sub-Investigator:
          • Dr Paraskevi Untiveros
    • Sutton Coldfield
      • Birmingham, Sutton Coldfield, United Kingdom, B75 7RR
        • Recruiting
        • Good Hope Hospital
        • Principal Investigator:
          • Dr Manoj Raghavan
        • Contact:
        • Sub-Investigator:
          • Dr Sophie Lee
        • Sub-Investigator:
          • Dr Harshini Alwis

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria (for Randomisation):

  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 (For Randomisation):

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: VBaP
Combination of sodium valproate, bezafibrate, medroxyprogesterone
Drug: 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)
Experimental: Danzol
Single agent
Drug: Danazol
Danazol 1 x 200mg capsules tds, (starting 1 x 200mg od)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
12 months
Duration of haematological response
Time Frame: 12 months
Clinically meaningful haematological responses that persist for 16 weeks or longer.
12 months
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) 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.
12 months
Overall survival
Time Frame: Through study completion, an average of 1 year
Overall survival at close of trial will be reported separately for each trial arm
Through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Prof. Janet Dunn

Collaborators

King's College Hospital NHS Trust
University of Manchester
University of Birmingham
Blood Cancer UK
Dudley Group NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 21, 2021

Primary Completion (Estimated)

January 31, 2025

Study Completion (Estimated)

June 30, 2025

Study Registration Dates

First Submitted

July 23, 2021

First Submitted That Met QC Criteria

August 9, 2021

First Posted (Actual)

August 10, 2021

Study Record Updates

Last Update Posted (Actual)

October 3, 2023

Last Update Submitted That Met QC Criteria

October 2, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SOC.11/20-21
  • 2020-005446-42 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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