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

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

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.

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.

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