Individual Molecular MRD Monitoring for MDS Patients After Allo-SCT

• Conditions: MRD; SCT; MDS

• Registration Number: NCT02872662
• Lead Sponsor: Nordic MDS Group

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.

Study Timeline

• Study First Submitted: 2016-05-02
• Study Start: 2016-08
• Study First Submitted QC: 2016-08-15
• Study First Posted: 2016-08-19
• Status Verified: 2018-01
• Last Update Submitted: 2018-01-29
• Last Update Posted: 2018-01-30
• Primary Completion: 2019-08
• Study Completion: 2019-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

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

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Exclusion Criteria

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Level of variant allele frequency (MRD) associated with full hematological relapse	From inclusion up to end of study (August 2019)	MRD is a quantative variable defined as variant allele frequency of patient-specific mutations. The association between MRD and relapse and survival will be studied.

Trial Locations

Locations (8)

Department of Medcine, Haukeland University Hospital; 🇳🇴 Bergen, Norway

Department of Hematology, Lund University Hospital; 🇸🇪 Lund, Sweden

Department of Hematology, Rigshospitalet Univsersity Hospital; 🇩🇰 Copenhagen, Denmark

Department of Hematology, Karolinska University Hospital; 🇸🇪 Stockholm, Sweden

Department of Hematology, Rikshospitalet University Hospital; 🇳🇴 Oslo, Norway

Department of Hematology, Aarhus University Hospital; 🇩🇰 Aarhus, Denmark

Department of Hematology and Coagulation, Sahlgrenska University hospital; 🇸🇪 Gothenburg, Sweden

Department of Hematology, Akademiska University Hospital; 🇸🇪 Uppsala, Sweden