Next Generation Sequencing (NGS) in Familial Acute Myeloid Leukemia and Myelodisplastic Syndromes

NCT03058588 | Recruiting

• 1 other identifier: NEXT-FAMLY 1016
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to look for predisposing mutations in patients and relatives affected by AML and MDS with familial history of myeloid or, less frequently, lymphoid malignancies. Taking advantage of a next generation sequencing (NGS) platform, screening for known and unknown mutations potentially associated with the disease will be done. The screening will be performed on affected and unaffected family members, in order to outline new pedigrees that either validate previous findings or constitute novel discoveries.

Conditions

Leukemia

Outcome Measures

Primary Outcomes (1)

• Discovery of predisposing mutations

  Screening of tumor and germline DNA for predisposing mutations

  After enrollment of the first 10 cases (an avarage of 2 years)

Study Arms (1)

Analysis with molecular biology

Any patient with acute leukemia or other myeloid malignancy AND 1. a first- or second-degree relative with acute leukemia or other myeloid malignancies 2. a first- or second-degree relative with lymphoproliferative neoplasms 3. or with clinical features that resemble one of the familial myeloid malignancies predisposition syndromes

Genetic: Analysis with molecular biology

Interventions

Analysis with molecular biology GENETIC

Molecular screening by next generation sequencing (NGS) platform, for known and unknown mutations potentially associated with the disease

Analysis with molecular biology

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Detailed personal and family history from every patient affected by myeloid malignancy will be obtained, in order to identify patients with at least one relative affected by myeloid malignancy or lymphoproliferative disorders or with the features that increase the likelihood of one of the aforementioned familial myeloid malignancy predisposition syndromes

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia: lead

Study Sites (1)

Chair of Hematology and Bone marrow Transplant Unit

Brescia, 25123, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Tumor DNA of index case will be extracted from 10 ml of PB collected at diagnosis in EDTA tubes. Mononuclear cells from PB (PBMC)will be separated and isolated by Ficoll gradient. Tumor DNA will be extracted possibly soon after the isolation. Tumor DNA of affected relative/-s will be extracted from PBMC isolated at diagnosis, or during the patients monitoring, and stored at -80°C. Tumor DNA previously extracted and stored at -20°C may be used in event of no PB or bone marrow sample available. Germline DNA of index case and relatives will be extracted by buccal epithelial cells isolated by Isohelix SK-2 DNA Buccal Swab Collection Kit by Therapak Corporation, Isohelix SK-2 DNA Buccal Swab Collection Kit.

MeSH Terms

Conditions

Leukemia

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Domenico Russo, MD

  Chair of Hematology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Domenico Russo, MD

CONTACT

0039303996811; domenico.russo@unibs.it

Francesca Schieppati, MD

CONTACT

0039303996811; fschieppati@gmail.com

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor of Hematology

Study Record Dates

• First Submitted: February 9, 2017
• First Posted: February 23, 2017
• Study Start: February 9, 2017
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 30, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)