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

NCT03154385 | Completed DMC

• 1 other identifier: P130408
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Immune Thrombocytopenia

Keywords

ITP

Outcome Measures

Primary Outcomes (1)

• The total number of patient responses to treatment, in other words sum of complete responses + responders

  A responder (R) to treatment is defined by a patient with a maintained platelet count at \>30x109/L (Rodeghiero et al Blood 2008) and a minimum twofold increase from initial platelet levels in the absence of bleeding and/or use of ITP directed therapies between Week 6 and Week 52 of patient follow-up. A complete response (CR) is defined by a platelet count \> 100 x 109/L maintained in the absence of any other ITP directed therapies between Week 6 and Week 52. A Non-Responder (NR) is a patient with one or all of the following : 1. Platelet count less than \< 30 x 109/L by the end of study 2. Require a rescue therapy (a new course of corticosteroids and/or intravenous immunoglobulin) more than 6 weeks after inclusion. 3. Underwent any other treatment for ITP over the study period

  Week 52

Secondary Outcomes (7)

• Number of patients developing a severe hypogammaglobulinemia (gammaglobulin level < 4 g/dl)

  at weeks 12, 24, 36, and 52

• Evolution of gammaglobulin levels

  at weeks 4, 8, 12, 24, 36, and 52

• Duration of severe hypogammaglobulinemia in patients with such complication

  Week 24

• Variation in gammaglobulin subclass levels throughout the study

  at weeks 0,12, 24, 36, 52

• Number of severe infections requiring hospitalization

  at weeks 24, 36 and 52

Study Arms (1)

arm 1

EXPERIMENTAL

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

Drug: Rituximab (Mabthera ®) Belimumab (Benlysta ®)

Interventions

Rituximab (Mabthera ®) Belimumab (Benlysta ®) DRUG

Rituximab (Mabthera ®): 1g IV at W0 and W2 Belimumab (Benlysta ®) : 10mg/kg IV, W0 + 2days, W2 + 2 days, W4, W8, W12

arm 1

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, \<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.
• 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

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Henri Mondor Hospital

Créteil, 94010, France

Location

Related Publications (1)

• Mahevas M, Azzaoui I, Crickx E, Canoui-Poitrine F, Gobert D, Languille L, Limal N, Guillaud C, Croisille L, Jeljeli M, Batteux F, Baloul S, Fain O, Pirenne F, Weill JC, Reynaud CA, Godeau B, Michel M. Efficacy, safety and immunological profile of combining rituximab with belimumab for adults with persistent or chronic immune thrombocytopenia: results from a prospective phase 2b trial. Haematologica. 2021 Sep 1;106(9):2449-2457. doi: 10.3324/haematol.2020.259481.

  PMID: 32817288 DERIVED

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic

Interventions

Rituximab; belimumab

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)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

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

Study Record Dates

• First Submitted: April 13, 2017
• First Posted: May 16, 2017
• Study Start: March 13, 2017
• Primary Completion: November 13, 2019
• Study Completion: November 13, 2019
• Last Updated: February 18, 2020

Record last verified: 2020-02

Locations

FR (1)