Repurposed Drugs to Improve Haematological Responses in Myelodysplastic Syndromes

Launched by PROF. JANET DUNN · Aug 9, 2021

Keywords

ClinConnect Summary

The REPAIR-MDS trial is investigating whether repurposed drugs can help improve blood cell production and overall health in patients with Myelodysplastic Syndromes (MDS). MDS is a condition affecting the bone marrow, leading to problems like fatigue, bleeding, and infections. This trial aims to see if a combination of three existing medications (sodium valproate, bezafibrate, and medroxyprogesterone) can be more effective than another drug called danazol for patients who have not responded to standard treatments aimed at boosting blood cell production.

To participate in the trial, individuals must be at least 18 years old and have a confirmed diagnosis of MDS, with specific blood-related issues. Key requirements include having low levels of hemoglobin, platelets, or neutrophils, and not responding to Erythropoiesis Stimulating Agents (drugs used to stimulate blood production). Participants can expect to receive one of the two treatment options and will be closely monitored throughout the study. This trial is currently recruiting and seeks to improve the quality of life for those living with MDS, potentially preventing the disease from progressing to a more severe form called acute myeloid leukemia (AML).

Gender

ALL

Eligibility criteria

• 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