Sponsor: Nordic MDS group
Project group:
Principal investigator: Dr Eva Hellström Lindberg (Karolinska, Huddinge)
Coordinator Sweden: Dr Magnus Tobiasson (Karolinska, Huddinge)
Coordinator Denmark: Dr Lone Smidstrup Friis (Rigshospitalet, Copenhagen)
Co-investigators: Dr Martin Jädersten (Karolinska, Huddinge), Dr Elisabeth Ejerblad (Uppsala), Dr Fryderyk Lorenz (Umeå), Dr Hege Garelius (Göteborg), Dr Lars Nilsson (Lund), Dr Petar Antunovic (Linköping), Dr Ingunn Dybedahl (Rikshospitalet, Oslo, PI Norway), Dr Astrid Olsnes Kittang (Bergen), Dr Lone Smidstrup Friis (Rigshospitaltet, Copenhagen, PI Denmark), Dr Lone Smidstrup Friis (Rigshospitalet, Copenhagen), Dr Gitte Olesen (Århus)
Genetic analyses: Professor Richard Rosenquist and Associate professor Lucia Cavalier (Uppsala)
Study design: Per Ljungman (Karolinska, Huddinge), Richard Rosenquist and Lucia Cavalier (Uppsala)
Experimental substudies: Sten-Eirik Jacobsen (Karolinska, Huddinge)
Study objectives:
- Phase I, year 1-2
Primary objectives:
1. To determine the predictive value, sensitivity and specificity of patient-specific molecular MRD markers for resistant disease and relapse in patients with MDS undergoing SCT.
Secondary objectives:
- To define cut-off values signalling impending relapse for the different mutations (e.g. different cut-offs for TP53 and TET2).
- To evaluate the sensitivity of MRD from peripheral blood samples compared to bone marrow samples.
- To determine the prognostic value of pre-treatment mutational profile for outcome after SCT.
- To, during this clinical trial, collect a biobank of consecutive blood and bone marrow samples from each patient allowing for studies of stem / progenitor cells, microenvironment and immune system before and after transplantation with regard to genetic, epigenetic and immunological features.
- Phase II, year 3-4
Primary objectives:
- After having the digital PCR method established as an accredited method allowing for results of the MRD analyses to be delivered to treating clinicians, we aim to evaluate the efficacy of pre-emptive treatment on the MDS-clone and the potential of avoiding relapse. Most likely, approaches will differ between different MDS subsets / molecular profiles. We will take the results from the first phase into account before outlining the next phase in detail and will after send in a new ethical application. The transition from phase I to phase II will be evaluated by a safety committee headed by an independent researcher.
Status: Study ready for inclusion
Start: Expected accrual time, FPI and LPI. Q3 2016 and Q3 2019
Inclusion criteria:
- Patients with MDS, MDS/MPN or AML with dysplastic features and 20-29% marrow blasts undergoing allogeneic stem cell transplantation.
- One or more mutations identified in the mutational screening.
- Written informed consent.
Contact person: Magnus Tobiasson
E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
