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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Charlotte Niemeyer, MD, University Hospital Freiburg
ClinicalTrials.gov Identifier:
NCT00499070
First received: July 10, 2007
Last updated: January 15, 2015
Last verified: January 2015
  Purpose

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.


Condition Intervention
Dyskeratosis Congenita
Fanconi Anemia
Myelodysplastic Syndromes
Pearson Marrow-pancreas Syndrome
Shwachman-diamond Syndrome
Genetic: polymerase chain reaction
Other: flow cytometry
Other: immunologic technique
Procedure: biopsy

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: TCR Vbeta Repertoire and PNH Clones in Children With Refractory Cytopenia (RC). An Open Nonrandomised Multi-Center Prospective Study

Resource links provided by NLM:


Further study details as provided by University Hospital Freiburg:

Primary Outcome Measures:
  • Number of patients with TCR V beta oligoclonality at diagnosis [ Time Frame: 96 months ] [ Designated as safety issue: No ]
  • Immunophenotype of patients with oligoclonal T-cell expansion [ Time Frame: 96 months ] [ Designated as safety issue: No ]
  • Number of patients with glycophosphatidylinositol (GPI) deficient clones [ Time Frame: 96 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of patients with molecular response as compared to hematological response after IST [ Time Frame: 96 months ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 96 months ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 96 months ] [ Designated as safety issue: No ]
  • Failure-free survival [ Time Frame: 96 months ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Bone Marrow Peripheral blood cells


Enrollment: 119
Study Start Date: January 2007
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    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 TCRVβ repertoire skewing. Comparison between BM and PB will identify which is the optimal compartment to analyze the responsible hematopoietic clones.
    Other: immunologic technique Procedure: biopsy
Detailed 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.

  Eligibility

Ages Eligible for Study:   up to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

All patients with MDS

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00499070

Locations
Austria
St. Anna Children's Hospital
Vienna, Austria, A-1090
Belgium
Ghent University
Ghent, Belgium, B-9000
Czech Republic
University Hospital Motol
Prague, Czech Republic, 150 06
Denmark
Arhus Universitetshospital - Skejby
Aarhus, Denmark, 8200
Germany
Universitaetskinderklinik - Universitaetsklinikum Freiburg
Freiburg, Germany, D-79106
Ireland
Our Lady´s Hospital for Sick Children
Dublin, Ireland, 12
Italy
Fondazione I.R.C.C.S. Policlinico San Matteo
Pavia, Italy, 27100
Netherlands
Erasmus MC - Sophia Children's Hospital
Rotterdam, Netherlands, 3015 GJ
Spain
Hospital Sant Joan de Deu
Barcelona, Spain, 08950
Switzerland
University Children's Hospital
Zurich, Switzerland, CH-8032
Sponsors and Collaborators
University Hospital Freiburg
Investigators
Study Chair: Marry M. Van Den Heuvel-Eibrink, MD, PhD Erasmus MC - Sophia Children's Hospital
  More Information

Additional Information:
No publications provided by University Hospital Freiburg

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Charlotte Niemeyer, MD, MD Prof. Dr. med. Niemeyer, University Hospital Freiburg
ClinicalTrials.gov Identifier: NCT00499070     History of Changes
Other Study ID Numbers: CDR0000553058, EWOG-MDS-RC-06
Study First Received: July 10, 2007
Last Updated: January 15, 2015
Health Authority: Germany: Ethics Commission

Keywords provided by University Hospital Freiburg:
refractory cytopenia with multilineage dysplasia
aplastic anemia
Fanconi anemia
dyskeratosis congenita
Shwachman-Diamond syndrome
Pearson marrow-pancreas syndrome

Additional relevant MeSH terms:
Bone Marrow Diseases
Dyskeratosis Congenita
Exocrine Pancreatic Insufficiency
Fanconi Anemia
Fanconi Syndrome
Lipid Metabolism, Inborn Errors
Lipomatosis
Mitochondrial Diseases
Muscular Diseases
Myelodysplastic Syndromes
Preleukemia
Syndrome
Anemia
Anemia, Aplastic
Anemia, Hypoplastic, Congenital
Congenital Abnormalities
DNA Repair-Deficiency Disorders
Digestive System Diseases
Disease
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Hematologic Diseases
Kidney Diseases
Lipid Metabolism Disorders
Metabolic Diseases
Metabolism, Inborn Errors
Musculoskeletal Diseases
Neoplasms
Nervous System Diseases
Neuromuscular Diseases

ClinicalTrials.gov processed this record on April 19, 2015