Rituximab, Eltrombopag and Dexamethasone as Frontline Treatment for Immune Thrombocytopenia

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the response rate and response duration with the combination of low-dose rituximab, eltrombopag and high-dose dexamethasone.

Detailed Description
-----------------
Immune thrombocytopenia is an autoimmune disorder characterized by formation of autoantibodies against platelet antigens leading platelet destruction. 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. Eltrombopag, it is a small molecule agonist of the c-mpl (TpoR) receptor, which is the physiological target of the hormone thrombopoietin, has been shown to be effectively raise the platelet count in adult patients (aged 18 years and over) who have had their spleen removed or where splenectomy is not an option and have received prior treatment with corticosteroids or immunoglobulins, and these medicines did not work (refractory ITP). There are a few case reports where eltrombopag was an option as first line treatment for IT. The purpose of this study is to determine the response rate and response duration with the combination of rituximab (100 mg weekly four weeks), eltrombopag (50mg PO once a day, day 1-28) and high-dose dexamethasone (40mg PO days 1-4) in untreated adult patients with <30*109/L platelet count diagnosed with immune thrombocytopenia. A complete response is defined as an increase in platelet counts to >150×109/L on two consecutive occasions. A clinical response is defined as an increase in the platelet count between >30×109/L on two consecutive measures and no bleeding. Duration of response is considered from the day of the initial administration to the first time of relapse (platelet count <30×109/L) or to time of analysis Patients will be evaluated each week during 4 weeks and then every month for at least 6 months.

Official Title
-----------------
Low-dose Rituximab in Combination With Eltrombopag and High-dose Dexamethasone as Frontline Treatment for Immune Thrombocytopenia

Conditions
-----------------
Immune Thrombocytopenia

Intervention / Treatment
-----------------
* Drug: Rituximab
* Drug: Eltrombopag
* Drug: Dexamethasone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinically confirmed immune thrombocytopenic (IT) Platelet count less than 30,000/mm3 on two ocasionts with bleeding. Subject ≥ 16 years Subject has signed and dated written informed consent. No sepsis or fever or active infection Not pregnant or nursing Exclusion Criteria: Previous treatment (only corticosteroids at dose or prednisone equivalent of 300 mg) Performance status above or equal to 2. Pregnancy and lactation Previous splenectomy Connective tissue disease Autoimmune hemolytic anemia Relapse

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rituximab, eltrombopag and dexamethasone<br>Each patient will receive Rituximab 100 mg weekly days 1, 7, 14, 21 Eltrombopag 50 mg PO days 1-28 Dexamethasone 40 mg IV/PO days 1-4 | Drug: Rituximab<br>* Rituximab 100 mg weekly days 1, 7, 14, 21<br>Drug: Eltrombopag<br>* Eltrombopag 50 mg PO days 1-28<br>Drug: Dexamethasone<br>* Dexamethasone 40 mg IV/PO days 1-4<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response | Platelet counts to >30×109/L on two consecutive occasions | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response | Platelet counts to >100×109/L on two consecutive occasions | 28 days |