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

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

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.

Study Overview

• Status: Completed
• Conditions: Immune Thrombocytopenia
• Intervention / Treatment: Other: blood sample

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Créteil, France, 94010
    • Henri Mondor Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: patients with rituximab treatment; blood sample intake	Other: blood sample

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
Rate of complete response (platelet count > 100 x 109/L)	at 1 year

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: MICHEL Marc, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2012
• Primary Completion (Actual): October 2, 2015
• Study Completion (Actual): October 2, 2015

Study Registration Dates

• First Submitted: November 6, 2014
• First Submitted That Met QC Criteria: November 10, 2014
• First Posted (Estimate): November 11, 2014

Study Record Updates

• Last Update Posted (Actual): October 19, 2017
• Last Update Submitted That Met QC Criteria: October 18, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Rituximab; ITP; Immune thrombocytopenia; Fc gamma RIIIA V/F158 polymorphism; autoreactive B and T cells
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia
• Other Study ID Numbers: P100119