Low-dose Rituximab and High-dose Dexamethasone as First Line Treatment for ITP

Study Overview
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Brief Summary
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The purpose of this study is to determine the response rate and response duration with the combination of low-dose rituximab and high-dose dexamethasone in the treatment of adult immune thrombocytopenic purpura.

Detailed Description
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ITP is an autoimmune disorder characterized by formation of autoantibodies against platelet antigens leading platelet destruction and bleeding. Corticosteroids increase the platelet count in about 80 percent of patients.However, many patients have a relapse when the dose of corticosteroid is reduced. Debilitating side effects are common in patients who require long-term corticosteroid therapy to maintain the platelet count. Rituximab, a chimeric anti-CD20 monoclonal antibody, has been shown to be effectively raise the platelet count in some patients with ITP and there is clinical and biological evidence to suggest that, if given early, rituximab may prevent ITP relapses. Rituximab 375 mg/m2 weekly for four weeks has significant activity in patients with immune thrombocytopenia. Furthermore, using lower dose rituximab the level of B-cell depletion and the response rates appear similar to those previously observed with standard dosages in a population of ITP. The purpose of this study is to determine the response rate and response duration with the combination of low-dose rituximab (100mg IV days 1,8, 15 and 22) and high-dose dexamethasone (40mg PO days 1,2,3,4) in untreated adult patients immune thrombocytopenic purpura. A complete platelet response is defined as an increase in platelet counts to >150×109/L on two consecutive occasions. A partial response is defined as an increase in the platelet count to between 50 and 150×109/L on two consecutive occasions, 1 week apart. Duration of response is considered from the day of the initial infusion to the first time of relapse (platelet count <30×109/L)or to time of analysis.

Official Title
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Low-dose Rituximab and High-dose Dexamethasone as First Line Treatment for Adult Patients With Immune Thrombocytopenic Purpura.

Conditions
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Immune Thrombocytopenic Purpura

Intervention / Treatment
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* Drug: Rituximab and dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically confirmed immune thrombocytopenic purpura (ITP) Platelet count less than 30,000/mm3 on two occasions. Platelets >30000/mm3 with bleeding. Normal to increased numbers of megakaryocytes on bone marrow examination in patients ≥ 60 years Subject is ≥ 18 years Subject has signed and dated written informed consent. No sepsis or fever No active infection requiring therapy No active chronic viral infection HIV negative Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Exclusion Criteria: Performance status above or equal to 2. Previous treatment with rituximab Immunosuppressive treatment within the last month Previous splenectomy Presence of malignant haematological disease Connective tissue disease Autoimmune hemolytic anemia Pregnancy and lactation Not willing to participate in the study. Expected survival of < 2 years Known intolerance to murine antibodies.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Rituximab -dexamethasone<br>only one arm receive four doses weekly rituximab and four dosis daily dexamethasona | Drug: Rituximab and dexamethasone<br>* Rituximab 100mg IV days 1,8,15,22. Dexamethasone 40mg PO days 1-4 (four days)<br>* Other names: Mabthera;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with sustained response after 6 months | Number of patients with partial and complete response after 6 months. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with complete response at month 6 | Number of patients with platelet count at least 150x109/L, 6 months after therapy | month 6 | 
| Bleeding | Number of patients with bleeding complication after therapy | month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rituximab, Dexamethasone, Low-dose, ITP