Dyskeratosis CongenitaNCT00499070
Assessing Immune Function in Young Patients With Cytopenia That Did Not Respond to Treatment
An observational study of Dyskeratosis Congenita and Fanconi Anemia, run by University Hospital Freiburg at 10 sites in 10 countries.
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. Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Dyskeratosis Congenita, Fanconi Anemia, Myelodysplastic Syndromes
- What is being tested?
- polymerase chain reaction, flow cytometry and immunologic technique
- Type of treatment
- Surgery or procedure
- How many people
- 119 participants
- Where
- 10 sitesin 10 countries
- Study dates
- Jan 2007to Aug 2012
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 17 years
- All sexes
- No healthy volunteers
- Child
Study population: All patients with MDS
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
Trial locations and contacts
10 sites in 10 countries.
10 sites in 10 countries
Germany1 site
Universitaetskinderklinik - Universitaetsklinikum Freiburg
Freiburg im Breisgau, D-79106
Netherlands1 site
Erasmus MC - Sophia Children's Hospital
Rotterdam, 3015 GJ
About this study
Official title: TCR Vbeta Repertoire and PNH Clones in Children With Refractory Cytopenia (RC). An Open Nonrandomised Multi-Center Prospective Study
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.
Read the 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.
- Conditions
- Dyskeratosis Congenita, Fanconi Anemia, Myelodysplastic Syndromes, Pearson Marrow-pancreas Syndrome, Shwachman-diamond Syndrome
- Being tested
- polymerase chain reaction, flow cytometry, immunologic technique, biopsy
- Keywords
- refractory cytopenia with multilineage dysplasia, aplastic anemia, Fanconi anemia, dyskeratosis congenita, Shwachman-Diamond syndrome, Pearson marrow-pancreas syndrome
- Medical subject headings
- Dyskeratosis Congenita, Fanconi Anemia, Myelodysplastic Syndromes, VLCAD deficiency, Shwachman-Diamond Syndrome, Anemia, Aplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
polymerase chain reactionGenetic
flow cytometryOther
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.
immunologic techniqueOther
biopsyProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with TCR V beta oligoclonality at diagnosis
Measured: 96 months
Immunophenotype of patients with oligoclonal T-cell expansion
Measured: 96 months
Number of patients with glycophosphatidylinositol (GPI) deficient clones
Measured: 96 months
Secondary outcomes (4)
Number of patients with molecular response as compared to hematological response after IST
Measured: 96 months
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
Measured: 96 months
Overall survival
Measured: 96 months
Failure-free survival
Measured: 96 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2007 (estimated)
- Study startJan 2007
- Primary completionAug 2012
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Dyskeratosis CongenitaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 119 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Freiburg
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Charlotte Niemeyer, MD, University Hospital Freiburg
- Investigators
- Marry M. Van Den Heuvel-Eibrink, MD, PhD, Study chair, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00499070
- Sponsor's protocol ID
- CDR0000553058
- Other IDs
- EWOG-MDS-RC-06
- Status last verified
- Jan 2015
- First submitted
- 10 Jul 2007
- Last updated
- 16 Jan 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Aalbers AM, van den Heuvel-Eibrink MM, Baumann I, Dworzak M, Hasle H, Locatelli F, De Moerloose B, Schmugge M, Mejstrikova E, Novakova M, Zecca M, Zwaan CM, Te Marvelde JG, Langerak AW, van Dongen JJ, Pieters R, Niemeyer CM, van der Velden VH. Bone marrow immunophenotyping by flow cytometry in refractory cytopenia of childhood. Haematologica. 2015 Mar;100(3):315-23. doi: 10.3324/haematol.2014.107706. Epub 2014 Nov 25.
PubMed 25425683Aalbers AM, van den Heuvel-Eibrink MM, Baumann I, Beverloo HB, Driessen GJ, Dworzak M, Fischer A, Gohring G, Hasle H, Locatelli F, De Moerloose B, Noellke P, Schmugge M, Stary J, Yoshimi A, Zecca M, Zwaan CM, van Dongen JJ, Pieters R, Niemeyer CM, van der Velden VH, Langerak AW. T-cell receptor Vbeta skewing frequently occurs in refractory cytopenia of childhood and is associated with an expansion of effector cytotoxic T cells: a prospective study by EWOG-MDS. Blood Cancer J. 2014 May 2;4(5):e209. doi: 10.1038/bcj.2014.28.
PubMed 24786393
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TCR Vbeta Repertoire and PNH Clones in Children With Refractory Cytopenia (RC). An Open Nonrandomised Multi-Center Prospective Study
- ClinicalTrials.gov ID
- NCT00499070
- Acronym / sponsor ID
- CDR0000553058
- Conditions
- Dyskeratosis Congenita, Fanconi Anemia, Myelodysplastic Syndromes, Pearson Marrow-pancreas Syndrome, Shwachman-diamond Syndrome
- Keywords
- refractory cytopenia with multilineage dysplasia, aplastic anemia, Fanconi anemia, dyskeratosis congenita, Shwachman-Diamond syndrome, Pearson marrow-pancreas syndrome
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 119 participants (actual)
- Lead sponsor
- University Hospital FreiburgUniversity, hospital or other
- Study start
- Jan 2007
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 11 Jul 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- All patients with MDS
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| polymerase chain reaction | Genetic | – |
| flow cytometryFor 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 | Other | – |
| biopsy | Procedure or surgery | – |
Primary outcome
Number of patients with TCR V beta oligoclonality at diagnosis
Time frame: 96 months
Immunophenotype of patients with oligoclonal T-cell expansion
Time frame: 96 months
Number of patients with glycophosphatidylinositol (GPI) deficient clones
Time frame: 96 months
4 secondary outcomes
Number of patients with molecular response as compared to hematological response after IST
Time frame: 96 months
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
Overall survival
Time frame: 96 months
Failure-free survival
Time frame: 96 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2015.
- Derived from this study: PubMed 25425683Aalbers AM, van den Heuvel-Eibrink MM, Baumann I, Dworzak M, Hasle H, Locatelli F, De Moerloose B, Schmugge M, Mejstrikova E, Novakova M, Zecca M, Zwaan CM, Te Marvelde JG, Langerak AW, van Dongen JJ, Pieters R, Niemeyer CM, van der Velden VH. Bone marrow immunophenotyping by flow cytometry in refractory cytopenia of childhood. Haematologica. 2015 Mar;100(3):315-23. doi: 10.3324/haematol.2014.107706. Epub 2014 Nov 25.
- Derived from this study: PubMed 24786393Aalbers AM, van den Heuvel-Eibrink MM, Baumann I, Beverloo HB, Driessen GJ, Dworzak M, Fischer A, Gohring G, Hasle H, Locatelli F, De Moerloose B, Noellke P, Schmugge M, Stary J, Yoshimi A, Zecca M, Zwaan CM, van Dongen JJ, Pieters R, Niemeyer CM, van der Velden VH, Langerak AW. T-cell receptor Vbeta skewing frequently occurs in refractory cytopenia of childhood and is associated with an expansion of effector cytotoxic T cells: a prospective study by EWOG-MDS. Blood Cancer J. 2014 May 2;4(5):e209. doi: 10.1038/bcj.2014.28.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marry M. Van Den Heuvel-Eibrink, MD, PhD study chair
Erasmus Medical Center
10 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Dyskeratosis Congenita and Fanconi Anemia, run by University Hospital Freiburg at 10 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Austria, Belgium, Czechia, Denmark, Germany and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with TCR V beta oligoclonality at diagnosis (time frame: 96 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00499070, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2015.