Previous studies have shown that increase level of BAFF could promote the settlement of long-lived plasma cells in the spleen of ITP patients treated with anti-CD20. This single-center prospective pilot study, currently in phase IIa, will evaluate the efficacy of a rituximab and belimumab sequential combination treatment. Investigators plan to include 15 patients with persistent ITP over a 24-month inclusion period. Each patient will be followed for 1 year

This single-center prospective pilot study, currently in phase IIa, evaluates the efficacy of a rituximab and belimumab sequential combination treatment. Based on the Fleming method, this study scheme includes a single step method.

Eligible patients, having given consent and having been verified for inclusion criteria, will receive two intravenous perfusions of 1 g of Rituximab (Mabthera ®) at W0 and W2 coupled with 100 mg intravenous methylprednisone to avoid potential allergic reactions.

Five belimumab (Benlysta ®) injections will be administered (W0 + 2days, W2 + 2 days, W4, W8, W12) at 10mg/kg doses. The first two injections are administered 2 days after Rituximab perfusions. The adopted experimental scheme was once used to show use of belimumab in systemic lupus erythematosus in accordance with AMM regulation.

This phase II prospective single-center open-trial will be conducted at the National Referral Center for Adult Immune Cytopenia located in the Henri Mondor University Hospital. Investigators plan to include 15 patients with persistent ITP over an 24-month inclusion period. Each patient will be followed for 1 year

Inclusion Criteria:

• Age ≥ 18 years, <75 years
• Primary ITP diagnostic defined according to the standard definition criteria (Rodeghiero et al Blood 2008)
• Previous transient response to first-line treatments of corticosteroids and/or IgIV characterized by a rise of platelet levels > 30 G/L with at least a twofold increase from baseline levels followed by a relapse.
• Platelet count ≤ 30,000 /µL at inclusion or <50 G/L if presence of hemorrhagic events or other reason left up to investigator discretion.
• A persistent ITP active and existing for more than 3 months but less than 5 years from diagnosis.
• Normal Bone marrow smear for patients above 60 years of age
• Negative pregnancy test results for women of procreation age
• Gammaglobulin level > 7 g/L
• Informed consent

Exclusion Criteria:

• Splenectomy
• Previous treatment by Rituximab or any B-cell targeted therapy
• Previous treatment by cyclophosphamide
• No medical treatments of a therapeutic protocol nature within the last 30 days
• Previous anaphylactic shock
• Previous septic shock or severe sepsis
• Chronic and ongoing severe infection requiring treatment or hospitalization in the 60 days preceding inclusion.
• Severe acute infection within the last 4 weeks
• Use of parenteral antibiotics within 60 days current use of suppressive therapy for chronic infection such as tuberculosis, pneumocystis, cytomegalovirus, HSZ, herpes zoster, and atypical mycobacteria
• History of primary immunodeficiency, IgG level < 400 mg/dl and/or IgA level < 10 mg/dl
• Have evidence of serious suicide risk including any history of suicidal behavior in the last 6 months and/or any suicidal ideation in the last 2 months or who in the investigator's judgment, pose a significant suicide risk.
• Secondary ITP
• History of recurrent infections
• Neutrophils count < 1,000/mm3 at inclusion
• Positive HIV test and/or hepatitis virus C infection and/or positive hepatitis B virus surface antigen or core antibody (HbsAg or HBcAb)
• Impaired renal function as indicated by a serum creatinine level > 2 mg/dl
• New York Heart Classification III or IV heart disease
• Treatment by antiaggregant/antiplatelet or anti-vitamin K drug
• Previous history of malignancy in the last 5 years other than cutaneous carcinoma
• Previous history of severe psychiatric disorder or previous suicide attempts in the last 6 months or suicidal thoughts in the last 2 months leading up to inclusion
• Unable to comply with study and follow-up procedures due to psychiatric disorders or any other reason
• Alcohol or drug abuse or dependence, either current or within 1year
• Pregnancy or Breast-Feeding
• Live, attenuated vaccinations must be administered at least 30 days before inclusion in study
• History of significant medical illness or clinically significant laboratory abnormality (or planned surgical procedure) which in the opinion of the investigator would interfere with the study procedures and / or assessments or compromise subject safety