Efficacy and Safety Assessment of a Treatment Combining Rituximab and Belimumab in Adults With Persistent Immune Thrombocytopenia

• Status: Completed
• Trial end date: 2019-11-13
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Treatments: Belimumab; Rituximab

Criteria

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