Polymorphism and Auto-reactive B and T Cells Subsets in Adult's Immune Thrombocytopenia (ITP)

Immune Thrombocytopenia Clinical Trial

— Poly-ITP  

Official title:

Fc Gamma RIIIA V/F158 Polymorphism and Auto-reactive B and T Cells Subsets in Adult's Immune Thrombocytopenia (ITP) and Correlations With Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02287649
• Other study ID #: P100119
• Status: Completed
• Phase: N/A
• First received: November 6, 2014
• Last updated: October 18, 2017
• Start date: September 28, 2012
• Est. completion date: October 2, 2015

Study information

• Verified date: October 2017
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Aims of the study : 1) To determine whether the presence of the V158 allele of Fc gammaRIIIA gene is associated with a better outcome of Immune Thrombocytopenia (ITP) in adults and especially with a higher response-rate to rituximab. 2) To analyze the impact of therapy and especially rituximab on some B and T cells autoreactive subsets in the peripheral blood.

Patients and Methods :

Inclusion criteria : age ≥ 18 years, primary ITP defined according to the recent consensual criteria (Rodeghiero F et al. Blood 2009), active ITP defined as an ITP with a platelet count < 50 x 109/L requiring treatment, informed consent. Main exclusion criteria : secondary ITP.

Blood samples (serum, plasma, DNA) will be collected in every patient at time of inclusion (pre-treatment) and then sequentially at 3, 6 and 12 months after inclusion in patients treated with rituximab or during the remission phase for other treatments for immunological studies. When a marrow analysis is indicated, some marrow specimens will also be collected and studied and if a patient will have to undergo a splenectomy as a standard of care, some spleen specimens will also be collected. Fc gamma RIIIA V/F158 polymorphism will be assessed by means of an allele-specific PCR. The sequential analysis of anti-platelets (anti-GpIIbIIIa) antibodies producing B cells will be performed by means of flow cytometry and ELISPOT analysis. T cells subsets will be harvested in presence of GpIIbIIIa immunodominant peptides and and cytokines expression will be measured on supernatants on days 2 and 11 in vitro by using Luminex technology in order to characterize and distinguish TH1, TH2, TH17, TFH and Tregs subsets.

The primary outcome will be the overall response rate 1 year after inclusion defined by a platelet count > 30 x 109/L with at least a two-fold increase of the initial (pre-treatment) count. For the patients treated with rituximab as a standard of care, based on the overall expected response-rate (40-50%) and based on preliminary data on FcgammaRIIIA V/F158 distribution, the inclusion of 85 patients should be sufficient to show an association of the V158 allele and the response (b risk 20% and a 5%). Responders and non responders will be compared by non parametrical tests, a multivariate analysis will be than performed using a logistic regression model. The immunological data B and T cells subsets) obtained in both the responders and the non responders will be compared over time (To, M3, M6 and M12) by non parametrical matched tests.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: October 2, 2015
• Est. primary completion date: October 2, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years

• Primary ITP as defined by the internation consensus on terminology (Rodeghiero et al. Blood 2009) regardless the phase of the disease (newly-diagnosed, persistent of chronic ITP)

• active ITP defined by a platelet count < 50 x 109/L at time of inclusion with indication for treatment

• Informed consent

Exclusion Criteria:

• Secondary ITP

Related Conditions & MeSH terms

• Immune Thrombocytopenia
• Purpura, Thrombocytopenic, Idiopathic
• Thrombocytopenia

Intervention

Other:
• blood sample

Locations

Country	Name	City	State
France	Henri Mondor Hospital	Créteil

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The overall response rate to rituximab defined by a platelet count > 30 x 109/L with at least a two-fold increase of the initial (pre-treatment) count		1 year after inclusion
Secondary	Rate of complete response (platelet count > 100 x 109/L)		at 1 year