Individual Molecular MRD Monitoring for MDS Patients After Allo-SCT

NCT ID: NCT02872662

Last Updated: 2018-01-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

200 participants

Study Classification

OBSERVATIONAL

Study Start Date

2016-08-31

Study Completion Date

2019-08-31

Brief Summary

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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

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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.

Conditions

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MDS SCT MRD

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

\-
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Nordic MDS Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Eva Hellström-Lindberg, Prof

Role: PRINCIPAL_INVESTIGATOR

Karolinska Institutet

Locations

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Department of Hematology, Aarhus University Hospital

Aarhus, , Denmark

Site Status RECRUITING

Department of Hematology, Rigshospitalet Univsersity Hospital

Copenhagen, , Denmark

Site Status RECRUITING

Department of Medcine, Haukeland University Hospital

Bergen, , Norway

Site Status RECRUITING

Department of Hematology, Rikshospitalet University Hospital

Oslo, , Norway

Site Status RECRUITING

Department of Hematology and Coagulation, Sahlgrenska University hospital

Gothenburg, , Sweden

Site Status RECRUITING

Department of Hematology, Lund University Hospital

Lund, , Sweden

Site Status RECRUITING

Department of Hematology, Karolinska University Hospital

Stockholm, , Sweden

Site Status RECRUITING

Department of Hematology, Akademiska University Hospital

Uppsala, , Sweden

Site Status RECRUITING

Countries

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Denmark Norway Sweden

Central Contacts

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Magnus Tobiasson, PhD

Role: CONTACT

0046858580000

Facility Contacts

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Lars Kjeldsen

Role: primary

Astrid Olsnes Kittang

Role: primary

Eva Hellstrom-Lindberg

Role: primary

References

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Tobiasson M, Pandzic T, Illman J, Nilsson L, Westrom S, Ejerblad E, Olesen G, Bjorklund A, Olsnes Kittang A, Werlenius O, Lorentz F, Rasmussen B, Cammenga J, Weber D, Lindholm C, Wiggh J, Dimitriou M, Moen AE, Yip Lundstrom L, von Bahr L, Baltzer-Sollander K, Jadersten M, Kytola S, Walldin G, Ljungman P, Groenbaek K, Mielke S, Jacobsen SEW, Ebeling F, Cavelier L, Smidstrup Friis L, Dybedal I, Hellstrom-Lindberg E. Patient-Specific Measurable Residual Disease Markers Predict Outcome in Patients With Myelodysplastic Syndrome and Related Diseases After Hematopoietic Stem-Cell Transplantation. J Clin Oncol. 2024 Apr 20;42(12):1378-1390. doi: 10.1200/JCO.23.01159. Epub 2024 Jan 17.

Reference Type DERIVED
PMID: 38232336 (View on PubMed)

Other Identifiers

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NMDSG14B

Identifier Type: -

Identifier Source: org_study_id

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