Pilot Study of Rituximab for the Treatment of Acute Immune Thrombocytopenic Purpura (ITP)

Study Overview
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Brief Summary
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The purpose of this study is to assess the feasibility of a randomized, double blind, placebo controlled trial of add-on rituximab for non-splenectomized adults with acute immune thrombocytopenic purpura (ITP).

Detailed Description
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Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by severe thrombocytopenia and bleeding. With current standard therapies, adult-onset ITP tends to recur thus exposing patients to prolonged risks of hemorrhage and toxicities of standard treatments. 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. We have designed a randomized, double blind, placebo controlled pilot trial of rituximab for the treatment of non-splenectomized adults with acute ITP who are receiving standard treatments. The primary objectives of this trial are to determine the feasibility of recruitment, randomization and blinding; the safety of rituximab in ITP; and the event rate in the control group which will be used to calculate the sample size for a larger trial. Secondary objectives are to determine rates of 6-month event free survival where an event is defined as any of: a platelet count <50; the need for rescue treatment; or significant bleeding. Data from this pilot trial will inform the design of a larger phase III trial.

Official Title
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A Randomized, Double Blind, Placebo Controlled Pilot Trial of Rituximab for Non-splenectomized Adults With Acute Immune Thrombocytopenic Purpura Receiving Standard Treatment (R-ITP)

Conditions
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Purpura, Thrombocytopenic, Idiopathic

Intervention / Treatment
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* Drug: Rituximab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-splenectomized patients with acute ITP, where acute ITP is defined as a platelet count below 30 at the time that standard treatment was recommended by a physician and for which no treatment had been received for the preceding 30 days. Must be receiving standard ITP treatment. Exclusion Criteria: Cardiac arrhythmia. Uncontrolled hypertension or inability to hold antihypertensive medications for 12 hours prior to and throughout study drug infusions. Known coronary artery disease, angina pectoris or myocardial infarction within the last year. Significant pulmonary disease within the last year. Stroke, transient ischemic attack or venous thrombosis within the last year. Secondary causes of thrombocytopenia (splenomegaly [palpable spleen or radiologically confirmed >14 cm], drug-induced thrombocytopenia, hereditary thrombocytopenia, microangiopathic hemolytic anemia, myelodysplastic syndrome). Chronic lymphocytic leukemia or lymphoma. Active or metastatic cancer. History of hepatitis B or C or HIV. Active infection in the 4 weeks before randomization. Inherited coagulation factor deficiency. Aspirin, aspirin-containing compounds, salicylates, non-steroidal anti-inflammatory medications (NSAIDS) medications, clopidogrel or ticlopidine in the 7 days preceding study drug infusions; vitamin K antagonists (warfarin) in the 3 days preceding study drug infusions; unfractionated heparin or low molecular weight heparin in the 24 hours preceding study drug infusions. Elevated INR or prolonged PTT; LDH, serum creatinine, liver function tests (AST/SGOT, ALT/SGPT, alkaline phosphatase, total bilirubin) increased more than 1.5 times upper limit of normal. Prior rituximab treatment. Unable to schedule 4 weekly study infusions. Pregnancy or breastfeeding. Known sensitivity to murine proteins, Chinese Hamster Ovary (CHO) cell proteins or to any component of rituximab. Participation in another clinical trial. Geographic inaccessibility. Failure to provide written informed consent. Any additional laboratory test result, health related illness or other diagnosis which, in the opinion of the treating physician, may put the subject's health or safety at risk.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>Rituximab | Drug: Rituximab<br>* 375mg/m2 per week for 4 consecutive weeks<br>* Other names: Rituxan, Mabthera;|
| Placebo Comparator: B<br>Saline placebo iv infusion | Drug: Placebo<br>* Saline IV placebo once per week for 4 consecutive weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of recruitment |  | 3 years | 
| Degree of adherence to the study protocol |  | 3 years | 
| Event free survival in controls |  | 6 months | 
| Bleeding |  | 6 months | 
| rescue therapy |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet count response |  | 6 months | 
| Quality of life |  | 6 months | 
| Circulating CD-20 positive lymphocytes |  | 6 months | 
| Platelet associated IgG |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Idiopathic Thrombocytopenic Purpura, Rituximab, Feasibility study