COSI

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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) comparing a new pre-transplant consolidation therapy (called) Vyxeos compared with the current standard of care (intermediate dose cytarabine); Randomisation 2 (R2) comparing a new myeloablative conditioning regimen (thiotepa, fludarabine and busulphan called TBF) compared with the standard conditioning regimen (fludarabine and busulphan called FB4); and Randomisation 3 (R3) comparing a new reduced intensity conditioning regimen (thiotepa, fludarabine and busulphan called mini TBF) compared with the standard conditioning regimen (fludarabine and busulphan called FB2). Patients can either enter R1 and subsequently R2/R3 or be randomised to either R1 or R2/3.

Objectives:

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).
• R2 – the impact of the novel myeloablative conditioning regimen TBF compared with the standard myeloablative (FB4) conditioning regimen on OS in patients aged under 55 years.
• R3 – the impact of the novel reduced intensity conditioning regimen mini TBF with the standard reduced intensity conditioning regimen FB2 on OS in patients 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 160 patients in R1; 382 patients in R2; and 218 patients in R3

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:  Closed to Recruitment/In follow-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.