- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03058588
Next Generation Sequencing (NGS) in Familial Acute Myeloid Leukemia and Myelodisplastic Syndromes
Next Generation Sequencing (NGS) Approach to Study Known and New Germline Mutations in Familial Acute Myeloid Leukemia and Myelodisplastic Syndromes
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Patients with a diagnosis of AML or MDS with at least one relative affected by AL/MDS or, secondly, lymphoproliferative disorders, will be enrolled into the study, and will be referred to as the index case. The analysis will be performed both retrospectively and prospectively. A gene panel deep sequencing (GPDS) of the tumor DNA from peripheral blood of the index case at diagnosis will be performed in order to identify mutations in a number of genes known to be associated to myeloid malignancies, mainly: ASXL1, BCOR, NRAS, TP53, RUNX1, CEBPA, FLT3, EZH2, IDH1, IDH2, NPM1, DNMT3A, TET2, CBL, KRAS, ETV6, SF3B1, SRSF2, U2AF1, ZRSR2, GATA2, TERT, TERC, SRP72, and ANKRD26.
In case none of the known mutations is found by the GPDS, whole exome sequencing (WES) will be performed as second step on the tumor cells of the index case.
When one or multiple somatic mutations are found, a Sanger Sequencing (SS) on germline DNA from epithelial buccal cells of the index cases and affected relatives will be performed for the screening of the same somatic leukemic mutations on germline DNA. If the index case and affected relatives share the same mutations on the germline, the same germline mutations will be checked by SS in the unaffected family members.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Domenico Russo, MD
- Phone Number: 0039303996811
- Email: domenico.russo@unibs.it
Study Contact Backup
- Name: Francesca Schieppati, MD
- Phone Number: 0039303996811
- Email: fschieppati@gmail.com
Study Locations
-
-
-
Brescia, Italy, 25123
- Recruiting
- Chair of Hematology and Bone marrow Transplant Unit
-
Contact:
- Domenico Russo, MD
- Email: domenico.russo@unibs.it
-
Contact:
- Francesca Schieppati, MD
- Email: fschieppati@gmail.com
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion criteria:
Any patient with acute myeloid leukemia (AML) or Myelodisplastic Syndrome (MDS) with:
- a first- or second-degree relative with Acute leukemia or MDS or other myeloid malignancies
- a first- or second-degree relative with Lymphoproliferative neoplasms
or with clinical features that resemble one of the familial MDS/AML predisposition syndromes:
- History of thrombocytopenia and/or a clinical bleeding propensity (as in RUNX1, ANKRD26 or ETV6 germline mutations)
- Abnormal nails or skin pigmentation, oral leukoplakia, idiopathic pulmonary fibrosis, unexplained liver disease (as in TERT and TERC germline mutations)
- Lymphedema, atypical infections, immune deficiencies (as in GATA2 germline mutations)
Exclusion Criteria:
- any diagnosis other than acute myeloid leukemia (AML) or Myelodisplastic Syndrome (MDS);
- acute myeloid leukemia (AML) or Myelodisplastic Syndrome (MDS) without a first- or second-degree relative with Acute leukemia or MDS or other myeloid malignancies or without a first- or second-degree relative with Lymphoproliferative neoplasms or with clinical features that resemble one of the familial MDS/AML predisposition syndromes;
- unability to sign the informed consent
Study Plan
How is the study designed?
Design Details
- Observational Models: Family-Based
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Analysis with molecular biology
Any patient with acute leukemia or other myeloid malignancy AND
|
Molecular screening by next generation sequencing (NGS) platform, for known and unknown mutations potentially associated with the disease
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Discovery of predisposing mutations
Time Frame: After enrollment of the first 10 cases (an avarage of 2 years)
|
Screening of tumor and germline DNA for predisposing mutations
|
After enrollment of the first 10 cases (an avarage of 2 years)
|
Collaborators and Investigators
Investigators
- Principal Investigator: Domenico Russo, MD, Chair of Hematology
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NEXT-FAMLY 1016
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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