Repurposed drugs to improve blood counts and reduce transfusions in myelodysplastic syndromes
- Conditions
- Myelodysplastic syndromesCancer
- Registration Number
- ISRCTN15563554
- Lead Sponsor
- niversity of Warwick
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 120
Current participant inclusion criteria as of 14/06/2023:
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 3.5
4. Haematological parameters:
4.1. Mean haemoglobin < 100 g/l over 16 weeks (pre-transfusion) OR
4.2. Mean platelets < 100 x 109/L over 16 weeks + evidence of bleeding (assessed using the ISTH Bleeding Assessment Tool) OR
4.3. 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 guidelines (NB Patients with thrombocytopenia and/or neutropenia, without anaemia, are eligible as they are predicated not to respond).
6. Eastern Cooperative Oncology Group (ECOG) performance status 0-3
7. Expected survival > 12 months
Previous participant 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:
4.1. Mean haemoglobin <100 g/l over 16 weeks (pre-transfusion) OR
4.2. Mean platelets <100 x 10e9/l over 16 weeks + evidence of bleeding (assessed using the International Society on Thrombosis and Haemostasis (ISTH) Bleeding Assessment Tool) OR
4.3. Mean neutrophils <1.0 x 10e9/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 guidelines
6. Eastern Cooperative Oncology Group (ECOG) performance status 0-3
7. Expected survival >12 months
Current participant exclusion criteria as of 14/06/2023:
1. Abnormal liver function (if the patient has Gilbert’s syndrome, then abnormal direct bilirubin is an exclusion)
2. Cockcroft Gault CrCl < 20 ml/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, 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 or cerebrovascular disease - can still be entered
7. Currently receiving fibrate medications
8. Currently receiving sodium valproate, carbamazepine or phenytoin for the treatment of epilepsy
9. Prior cytotoxic chemotherapy or hypomethylating agents for AML/MDS (e.g. 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 direct oral anticoagulants (DOACs) can be included)
13. History of venous thromboembolism (VTE)
14. Cardiac failure NYHA Class III or IV
15. Women of childbearing potential, pregnant or lactating
16. The physician or patient considers 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
22. Previous randomisation in the REPAIR-MDS trial
23. Participation in a clinical trial of an investigational medicinal product in the last 16 weeks
Previous participant exclusion criteria:
1. Abnormal liver function (if the patient has Gilbert’s syndrome, then abnormal direct bilirubin is an exclusion)
2. Cockcroft Gault CrCl < 20 ml/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 or cerebrovascular 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)
7. Currently receiving fibrate medications
8. Currently receiving sodium valproate, carbamazepine or phenytoin for treatment of epilepsy
9. Prior cytotoxic chemotherapy for AML/MDS
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 direct oral anticoagulants (DOACs) can be included)
13. History of venous thromboembolism (VTE)
14. Cardiac failure NYHA Class III or IV
15. Women of
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 International Working Group (IWG) 2018 haematology response criteria in patients with MDS. Baseline assessment will be determined by the mean FBC parameters (haemoglobin, platelet and neutrophil counts) and transfusion burden (non-transfused [NTD], low transfusion burden [LTB], high transfusion burden [HTB]) during a 16-week lead-in to randomisation to either VBaP or danazol treatment; Timepoint(s): 12 months
- Secondary Outcome Measures
Name Time Method