Identification of Molecular Defects in Idiopathic Cytopenia of Undetermined Significance

Myelodysplastic Syndromes Clinical Trial

— AMICUS  

Official title:

Identification of Molecular Defects in Idiopathic Cytopenia of Undetermined Significance

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02804984
• Other study ID #: PI2014_843_0008
• Status: Recruiting
• Start date: July 2015
• Est. completion date: July 2019

Study information

• Verified date: August 2018
• Source: Centre Hospitalier Universitaire, Amiens
• Contact: Bérengère GRUSON, PhD
• Phone: +33 3 22 45 59 85
• Email: gruson.berengere[@]chu-amiens.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The project's objective is to identify and characterize somatic mutations in cases of idiopathic cytopenia of undetermined significance (ICUS) on the basis of molecular defects found in myelodysplastic syndrome (MDS), in order to validate the hypothesis whereby ICUS may be a precursor of MDS

Description:

The project's objective is to identify and characterize somatic mutations in cases of idiopathic cytopenia of undetermined significance (ICUS) on the basis of molecular defects found in myelodysplastic syndrome (MDS), in order to validate the hypothesis whereby ICUS may be a precursor of MDS. To this end, high-throughput exon sequencing (using next-generation sequencing (NGS)) will be used to target the genes known to be mutated in MDS. This study is important for two reasons. Firstly, it will help to optimise the clinical monitoring of patients with molecular defects and considered to be at risk of progression. Secondly, it will provide a better understanding of the fundamental molecular mechanisms underlying the progression of ICUS to MDS.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: July 2019
• Est. primary completion date: July 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age 18 or over.

• Haemoglobin <11 g/dl and/or a polynuclear neutrophil count <1.5.109/L and/or a platelet count <100.109/L

• Full clinical biochemistry/haematological profiling: complete blood count, blood smear, reticulocyte count, iron status, folates, B12, TSH, creatinine, liver enzymes, ANAs, rheumatoid factor, anticardiolipin antibodies, Coombs test, EPO assay, serological tests for HIV, HVB and HVC.

• Availability of a bone marrow differential cell count and an evaluation of myelopoiesis disorders (number of lineages, percentage of cells affected, etc.) plus Perls staining.

• Availability of a cytogenetic analysis.

• Voluntary provision of written, informed consent

• Life expectancy >6 months

• Social security coverage

Exclusion Criteria:

• An obvious cause of anaemia (if isolated): iron deficiency, chronic kidney failure (clearance <60 ml/min), regenerative anaemia (reticulocytes >150G/L)

• Vitamin B12 or B9 deficiency

• Hepatomegaly, or clinical and/or ultrasound signs of portal hypertension

• Clinical and/or ultrasound signs of splenomegaly

• Abnormal liver enzyme levels: total bilirubin, alkaline phosphatases or transaminases > 1.5N; gammaGT > 2N. A history of (or diagnostic criteria during screening) auto-immune diseases such as systemic erythematous lupus, antiphospholipid syndrome or Evans syndrome.

• An abnormal bone marrow differential cell count

• A bone marrow karyotype revealing MDS

• Medical, psychological or social conditions that prevent the participant from correctly understanding the study procedures.

• Legal guardianship and incarceration.

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Preleukemia

Intervention

Genetic:
• ICUS

Locations

Country	Name	City	State
France	CHU Amiens	Amiens

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire, Amiens

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	high-throughput sequencing	The presence or absence of one or several of the following molecular defects, as detected by high-throughput sequencing: DNMT3A, TET2, IDH1/2, ASXL1, EZH2, RUNX1, EVI1, GATA2, P53, JAK2, CBL, KRAS, SF3B1, SRSF2, U2AF1, and ZRSR2.	Day 0
Secondary	phenotypic defects	Analysis of phenotypic defects detected by flow cytometry.	Day 0
Secondary	growth of erythroid progenitors	Analysis of the growth of erythroid progenitors (BFU-E) and granulocyte-monocyte progenitors (CFU-GM).	Day 0
Secondary	Appearance of MDS	Appearance of MDS during follow-up: a bone marrow differential cell count at 6 months and whenever cytopenia appears.	6 months