Clinical trial NCT02872662: Individual Molecular MRD Monitoring for MDS Patients After Allo-SCT
Official title: Individual Molecular Minimal Residual Disease (MRD) Monitoring for Patients With MDS and Mixed MDS/MPN Treated With Allogeneic Stem Cell Transplantation
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: MDS
SCT
MRD
Lead sponsor: Nordic MDS Group
Sponsor class: NETWORK
First posted: 2016-08-19
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 200 consecutive MDS patients undergoing allogeneic SCT

Brief summary: This study aims to develop highly sensitive methods for early detection of relapse based on the patients unique mutations. Initially, a mutational screen is being performed. Primers directed against these mutations will be constructed and presence of mutations will be followed in bone marrow and blood frequently after transplantation.

Detailed description: This study aims to develop highly sensitive methods for early detection of relapse based on the patients unique mutations.

Screening of mutations In collaboration with Department for clinical genetics, Uppsala, an initial screening of mutations will be performed using the commercial TrueSight© sequencing panel which includes 54 genes recurrently mutated in myeloid diseases. Based on the mutations identified, PCR-primers for all patient-specific mutations will be designed. Patients without any mutation will be excluded from the study. The mutational screen is performed as soon as a patient is being identified as a potential candidate for allogeneic stem cell transplantation (SCT) and evaluated for most optimal pre-SCT treatment. The patient is included in the study before the bone marrow sampling preceding SCT. In case a mutational screen has not been performed before pre-SCT MDS treatment, a mutational screen from the diagnostic national biobank sample (peripheral blood) can be performed.

MRD surveillance After the transplantation, peripheral blood samples will be collected once monthly; and bone marrow samples will be collected at month 1, 3, 6 after SCT followed by sampling every third month until relapse or death. The samples are sent to Biobanking and Molecular Resource Infrastructure of Sweden (bbmri) who will extract DNA and store the samples. By using the highly sensitive digital-PCR method the investigators will determine the size of the different clones at the different time points. In addition to biobanking of DNA, bbmri will collect and vital froze mononuclear cells (MNCs) to be used for experimental studies.

Statistics Landmark analyses will be performed at different time points after SCT, using presence of MRDs as a risk factor included in a multivariate analysis. Furthermore, the investigators will calculate sensitivity, specificity and predictive value for MRDs in relation to relapse. For each specific mutation, with high enough frequency in the cohort, the investigators will define cut-off values of the MRD where relapse is impending.

Eligibility criteria: Inclusion Criteria:

1. MDS with allo SCT to be performed
2. One or more mutations identified
3. Written informed consent

Exclusion Criteria:

-

Primary outcomes:
measure: Level of variant allele frequency (MRD) associated with full hematological relapse
timeFrame: From inclusion up to end of study (August 2019)
Secondary outcomes:
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Department of Hematology, Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Department of Hematology, Rigshospitalet Univsersity Hospital
city: Bergen
country: Norway
facility: Department of Medcine, Haukeland University Hospital
city: Oslo
country: Norway
facility: Department of Hematology, Rikshospitalet University Hospital
city: Gothenburg
country: Sweden
facility: Department of Hematology and Coagulation, Sahlgrenska University hospital
city: Lund
country: Sweden
facility: Department of Hematology, Lund University Hospital
city: Stockholm
country: Sweden
facility: Department of Hematology, Karolinska University Hospital
city: Uppsala
country: Sweden
facility: Department of Hematology, Akademiska University Hospital
Study officials:
affiliation: Karolinska Institutet
name: Eva Hellström-Lindberg, Prof
role: PRINCIPAL_INVESTIGATOR
References: