COSI: An International Randomised Clinical Trial of Therapeutic Interventions with the Potential to Improve Outcome in Adults with Acute Myeloid Leukaemia and High Risk Myelodysplasia Undergoing Allogeneic Stem Cell TransplantatIon
Study design/summary: This is a randomised, international, phase II/III, multicentre, clinical trial in patients with acute myeloid leukaemia (AML) and myelodysplasia (MDS) undergoing allogeneic stem cell transplantation (allo-SCT). The trial has three possible randomisations (randomisation 1 (R1), randomisation 2 (R2) and randomisation 3 (R3)). Patients can either enter R1 and subsequently R2/R3 or be randomised to either R1 or R2/3.
Primary Objectives will be to study:
- R1 – the impact of the novel pre-transplant consolidation therapy Vyxeos compared with intermediate dose cytarabine on overall survival (OS) in patients with AML and high risk MDS with excess blasts. Secondary objectives are to determine the change in post-consolidation measurable residual disease (MRD) status, disease-free survival (DFS), cumulative incidence of disease relapse (CIR), non-relapse mortality (NRM) and incidence of toxicity (grade 3 or higher).
- R2 – the impact of the novel myeloablative conditioning regimen TBF compared with the standard myeloablative (FB4) conditioning regimen on OS in patients with AML and high risk MDS aged under 55 years.
- R3 – the impact of the novel reduced intensity conditioning regimens mini FLAMSA-BU or mini TBF with the standard reduced intensity conditioning regimen FB2 on OS in patients with AML and high risk MDS aged 55 years and over.
Secondary Objectives will be to determine:
- R1 – the change in post-consolidation measurable residual disease (MRD) status, disease-free survival (DFS), cumulative incidence of disease relapse (CIR), non-relapse mortality (NRM) and incidence of toxicity (grade 3 or higher).
- R2 and R3 – the DFS, CIR, NRM, quality of life (QoL), incidence of acute and chronic graft-versus-host-disease (GVHD), incidence of primary graft failure, and incidence of toxicity (grade 3 or higher).
Centres: 22 IMPACT centres
Target Number of patients: Up to 860 patients
Patient population: Adults with AML or high risk MDS considered suitable for an allo-SCT will be recruited to this trial.
Sponsorship/Funding: University of Birmingham, funded by the IMPACT network
Trial Status: In set-up
Duration: 6-7 years. Patients will be recruited over 48 months. Patients will be followed up for a minimum of 2 years.
Trial Contacts: COSI@trials.bham.ac.uk
If you are a patient and interested in taking part in a clinical trial, please speak with your consultant who will be able to offer you further information and discuss whether it is suitable for you. A referral from your medical team would be required in order to consider you for treatment on a clinical trial.