Assessing Immune Function in Young Patients With Cytopenia That Did Not Respond to Treatment

Myelodysplastic Syndromes Clinical Trial

Official title:

TCR Vbeta Repertoire and PNH Clones in Children With Refractory Cytopenia (RC). An Open Nonrandomised Multi-Center Prospective Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00499070
• Other study ID #: CDR0000553058
• Secondary ID: EWOG-MDS-RC-06
• Status: Completed
• Phase: N/A
• First received: July 10, 2007
• Last updated: January 15, 2015
• Start date: January 2007
• Est. completion date: August 2012

Study information

• Verified date: January 2015
• Source: University Hospital Freiburg
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Observational

Clinical Trial Summary

RATIONALE: Studying biopsy, bone marrow, and blood samples from patients with cytopenia that did not respond to treatment may help doctors learn more about the disease and plan the best treatment.

PURPOSE: This laboratory study is assessing immune function in young patients with cytopenia that did not respond to treatment.

Description:

OBJECTIVES:

Primary

• To evaluate the value of TCR V beta repertoire analysis for the determination of autoimmunity in refractory cytopenia (RC).

• To evaluate which immunophenotypic hematopoietic subclones are associated with oligoclonal T-cell expansion in RC.

• To evaluate the presence of paroxysmal nocturnal hemoglobinuria (PNH) clones in RC.

Secondary

• To compare the molecular response with the hematologic response in patients with RC after treatment with immunosuppressive therapy (IST).

• To compare the molecular response with human leukocyte histocompatability antigen (HLA) expression in patients with RC after treatment with IST.

OUTLINE: This is an open-label, multicenter, nonrandomized, prospective study.

Patients undergo biopsy, bone marrow, and blood sample collection periodically for immunological studies. Samples are analyzed for TCR V beta repertoire and paroxysmal nocturnal hemoglobinuria (PNH) clone analysis via PCR heteroduplex analysis and immunophenotyping of CD14, CD16 , CD55, CD59, and CD24 expression via flow cytometry.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 119
• Est. completion date: August 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 17 Years

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of refractory cytopenia (RC) including any of the following:

• Severe aplastic anemia (SAA)

• Fanconi's anemia

• Shwachman Diamond syndrome

• Dyskeratosis congenita

• Pearson syndrome

• All RC patients included in the EWOG MDS 2006 protocol irrespective of therapy

• Patients who have undergone hematopoietic stem cell transplantation (HSCT) may be enrolled on EWOG-MDS SCT RC RIC 06 or EWOG-MDS SCT MDS 06 protocol

PATIENT CHARACTERISTICS:

• Not specified

PRIOR CONCURRENT THERAPY:

• No prior immunosuppressive therapy for refractory cytopenia

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Bone Marrow Diseases
• Dyskeratosis Congenita
• Exocrine Pancreatic Insufficiency
• Fanconi Anemia
• Fanconi Syndrome
• Lipid Metabolism, Inborn Errors
• Mitochondrial Diseases
• Muscular Diseases
• Myelodysplastic Syndromes
• Pearson Marrow-pancreas Syndrome
• Preleukemia
• Shwachman-diamond Syndrome
• Syndrome

Intervention

Genetic:
• polymerase chain reaction

Other:
• flow cytometry
For analyzing GPI deficient clones full blood will be analyzed by phenotyping using flowcytometry. For that purpose CD14, CD16 and CD24 expression will be evaluated in CD45 positive cells. Erythroid cells will be evaluated for CD55 and CD59 expression searching for clear populations with a lack of GPI-linked molecules. In addition, immunophenotyping using flowcytometry will be performed to evaluate which differentiation stages of the major hematopoietic lineages in BM and PB are associated with TCRVß repertoire skewing. Comparison between BM and PB will identify which is the optimal compartment to analyze the responsible hematopoietic clones.
• immunologic technique

Procedure:
• biopsy

Locations

Country	Name	City	State
Austria	St. Anna Children's Hospital	Vienna
Belgium	Ghent University	Ghent
Czech Republic	University Hospital Motol	Prague
Denmark	Arhus Universitetshospital - Skejby	Aarhus
Germany	Universitaetskinderklinik - Universitaetsklinikum Freiburg	Freiburg
Ireland	Our Lady´s Hospital for Sick Children	Dublin
Italy	Fondazione I.R.C.C.S. Policlinico San Matteo	Pavia
Netherlands	Erasmus MC - Sophia Children's Hospital	Rotterdam
Spain	Hospital Sant Joan de Deu	Barcelona
Switzerland	University Children's Hospital	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Freiburg

Countries where clinical trial is conducted

Austria,  Belgium,  Czech Republic,  Denmark,  Germany,  Ireland,  Italy,  Netherlands,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with TCR V beta oligoclonality at diagnosis		96 months	No
Primary	Immunophenotype of patients with oligoclonal T-cell expansion		96 months	No
Primary	Number of patients with glycophosphatidylinositol (GPI) deficient clones		96 months	No
Secondary	Number of patients with molecular response as compared to hematological response after IST		96 months	No
Secondary	Number of patients with HLA-DR15 antigen expression and molecular response as compared to number of patients with other HLA-DR antigens and molecular response		96 months	No
Secondary	Overall survival		96 months	No
Secondary	Failure-free survival		96 months	No