Rituximab and Prednisone as First-Line Therapy in Treating Patients With Immune Thrombocytopenic Purpura

Study Overview
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Brief Summary
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RATIONALE: Rituximab and prednisone may increase the number of platelets in patients with immune thrombocytopenic purpura. PURPOSE: This phase II trial is studying the side effects and how well giving rituximab together with prednisone works as first-line therapy in treating patients with immune thrombocytopenic purpura.

Detailed Description
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OBJECTIVES: Primary Determine the efficacy of rituximab, when administered with standard prednisone treatment, in maintaining a platelet count ≥ 50,000/mm³ at 6 months without further therapies (e.g., splenectomy or other salvage therapies) in patients with immune thrombocytopenic purpura. Determine the safety of this regimen in these patients. Secondary Determine the time to platelet recovery in patients treated with this regimen. Determine the duration of platelet recovery in patients treated with this regimen. Assess efficacy of this regimen in preventing spontaneous bleeding events in these patients. Determine the response in patients treated with this regimen. OUTLINE: This is a pilot study. Patients receive rituximab IV on days 1, 8, 15, and 22 and oral prednisone once daily on days 1-14 followed by a taper to day 56. Treatment is administered in the absence of disease relapse or unacceptable toxicity. After completion of study therapy, patients are followed periodically for up to 3 years.

Official Title
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A Pilot Study of Rituximab in Combination With Corticosteroids for the Initial Treatment of Immune Thrombocytopenic Purpura

Conditions
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Nonneoplastic Condition

Intervention / Treatment
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* Biological: Rituximab
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of immune thrombocytopenic purpura (ITP) Diagnosis must be made according to American Society of Hematology diagnostic guidelines by a member of Mayo Rochester's Division of Hematology/Oncology within the past year ITP must be confirmed by bone marrow aspiration and biopsy in all patients ≥ 60 years of age* Bone marrow studies performed outside Mayo must be reviewed by a Mayo hematopathologist to confirm diagnosis and exclude evidence of other hematologic disorders NOTE: *Bone marrow evaluation is discretionary for all other patients Requires treatment, as defined by 1 of the following parameters: Platelet count ≤ 30,000/mm³ Platelet count ≤ 50,000/mm³ with episodic bleeding (i.e., spontaneous or with minimal trauma) requiring treatment No concurrent diagnosis of a condition known to cause secondary immune (or nonimmune) thrombocytopenia, including, but not limited to, any of the following: Rheumatological conditions, such as lupus, rheumatoid arthritis, scleroderma, or mixed connective tissue disorder Patients with positive serologies and no concurrent, clinically evident condition are eligible HIV positive or AIDS Non-Hodgkin's lymphoma, Hodgkin's lymphoma, chronic lymphocytic lymphoma, multiple myeloma, or other malignant hematological conditions Clinically evident antiphospholipid antibody syndrome* or heparin-induced thrombocytopenia Clinically overt liver disease, hepatitis B surface antigen positive, hepatitis C serology positive, or evidence of a microangiopathic hemolytic anemia, such as disseminated intravascular coagulation, hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura, or preeclampsia NOTE: *Positive laboratory tests without the defined clinical criteria for a diagnosis of antiphospholipid antibody syndrome is allowed PATIENT CHARACTERISTICS: ECOG performance status 0-2 Creatinine ≤ 2 times upper limit of normal (ULN) Direct bilirubin ≤ 1.5 times ULN Total bilirubin ≤ 1.5 times ULN AST ≤ 2.5 times ULN Hemoglobin ≥ 10 g/dL WBC ≥ 3,000/mm³ Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No hypersensitivity to murine or chimeric proteins No other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk for treatment complications Able to take a proton-pump inhibitor while on corticosteroids No unresolved or incompletely treated infection within the past 14 days PRIOR CONCURRENT THERAPY: No prior corticosteroid therapy since the diagnosis of ITP Corticosteroid therapy is allowed for up to 14 days prior to study entry, once the baseline CBC has been established No prior rituximab No other concurrent therapy for ITP, including androgens, IV immunoglobulins, RH_o (D) immune globulin, cyclosporine, or azathioprine sodium

Ages Eligible for Study
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Minimum Age: 21 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 |
| --- | --- |
| Experimental: PRED & RITUX<br> | Biological: Rituximab<br>* 375mg/m2 IV weekly times 4 (days 1, 8, 15, 22)<br>* Other names: Rituxan;Drug: Prednisone<br>* 1mg/kg/d PO, taper to off by 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Failure-free survival at 6 months |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to platelet recovery |  | 1 year | 
| Duration of platelet recovery |  | 1 year | 
| Effect of treatment on prevention of spontaneous bleeding events |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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idiopathic thrombocytopenic purpura