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

NCT02287649 | Completed DMC

• 1 other identifier: P100119
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Immune Thrombocytopenia

Keywords

Immune thrombocytopenia; Fc gamma RIIIA V/F158 polymorphism; Rituximab; autoreactive B and T cells; ITP

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Rate of complete response (platelet count > 100 x 109/L)

  at 1 year

Study Arms (1)

patients with rituximab treatment

OTHER

blood sample intake

Other: blood sample

Interventions

blood sample OTHER

patients with rituximab treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Informed consent

You may not qualify if:

• Secondary ITP

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Henri Mondor Hospital

Créteil, 94010, France

Location

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• MICHEL Marc

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2014
• First Posted: November 11, 2014
• Study Start: September 28, 2012
• Primary Completion: October 2, 2015
• Study Completion: October 2, 2015
• Last Updated: October 19, 2017

Record last verified: 2017-10

Locations

FR (1)