Individual Molecular MRD Monitoring for MDS Patients After Allo-SCT

MDS Clinical Trial

Official title:

Individual Molecular Minimal Residual Disease (MRD) Monitoring for Patients With MDS and Mixed MDS/MPN Treated With Allogeneic Stem Cell Transplantation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02872662
• Other study ID #: NMDSG14B
• Status: Recruiting
• Phase: N/A
• First received: May 2, 2016
• Last updated: January 29, 2018
• Start date: August 2016
• Est. completion date: August 2019

Study information

• Verified date: January 2018
• Source: Nordic MDS Group
• Contact: Magnus Tobiasson, PhD
• Phone: 0046858580000
• Email: magnus.tobiasson[@]ki.se
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: August 2019
• Est. primary completion date: August 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. MDS with allo SCT to be performed

2. One or more mutations identified

3. Written informed consent

Exclusion Criteria:

Related Conditions & MeSH terms

• MDS
• MRD
• SCT

Locations

Country	Name	City	State
Denmark	Department of Hematology, Aarhus University Hospital	Aarhus
Denmark	Department of Hematology, Rigshospitalet Univsersity Hospital	Copenhagen
Norway	Department of Medcine, Haukeland University Hospital	Bergen
Norway	Department of Hematology, Rikshospitalet University Hospital	Oslo
Sweden	Department of Hematology and Coagulation, Sahlgrenska University hospital	Gothenburg
Sweden	Department of Hematology, Lund University Hospital	Lund
Sweden	Department of Hematology, Karolinska University Hospital	Stockholm
Sweden	Department of Hematology, Akademiska University Hospital	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
Nordic MDS Group

Countries where clinical trial is conducted

Denmark,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Level of variant allele frequency (MRD) associated with full hematological relapse	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.	From inclusion up to end of study (August 2019)