Individual Molecular MRD Monitoring for MDS Patients After Allo-SCT

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

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.

Study Overview

• Status: Unknown
• Conditions: MDS; SCT; MRD

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 Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Magnus Tobiasson, PhD; Phone Number: 0046858580000; Email: magnus.tobiasson@ki.se

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Recruiting
    • Department of Hematology, Aarhus University Hospital
  • Copenhagen, Denmark
    • Recruiting
    • Department of Hematology, Rigshospitalet Univsersity Hospital
    • Contact: Lars Kjeldsen
• Norway
  • Bergen, Norway
    • Recruiting
    • Department of Medcine, Haukeland University Hospital
    • Contact: Astrid Olsnes Kittang
  • Oslo, Norway, 0027
    • Recruiting
    • Department of Hematology, Rikshospitalet University Hospital
• Sweden
  • Gothenburg, Sweden, 413 45
    • Recruiting
    • Department of Hematology and Coagulation, Sahlgrenska University Hospital
  • Lund, Sweden, 221 85
    • Recruiting
    • Department of Hematology, Lund University Hospital
  • Stockholm, Sweden
    • Recruiting
    • Department of Hematology, Karolinska University Hospital
    • Contact: Eva Hellstrom-Lindberg
  • Uppsala, Sweden, 751 85
    • Recruiting
    • Department of Hematology, Akademiska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

200 consecutive MDS patients undergoing allogeneic SCT

Description

Inclusion Criteria:

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

Exclusion Criteria:

-

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Collaborators and Investigators

• Sponsor: Nordic MDS Group
• Investigators: Principal Investigator: Eva Hellström-Lindberg, Prof, Karolinska Institutet

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Anticipated): August 1, 2019
• Study Completion (Anticipated): August 1, 2019

Study Registration Dates

• First Submitted: May 2, 2016
• First Submitted That Met QC Criteria: August 15, 2016
• First Posted (Estimate): August 19, 2016

Study Record Updates

• Last Update Posted (Actual): January 30, 2018
• Last Update Submitted That Met QC Criteria: January 29, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: NMDSG14B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Mutational data, MRD and clinical data is planned to be published