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.

Study Overview

• Status: Completed
• Conditions: Nonneoplastic Condition
• Intervention / Treatment: Biological: Rituximab; Drug: Prednisone

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 22
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRED & RITUX	Biological: Rituximab; 375mg/m2 IV weekly times 4 (days 1, 8, 15, 22); Other Names: Rituxan; Drug: Prednisone; 1mg/kg/d PO, taper to off by 8 weeks

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: June 13, 2007
• First Submitted That Met QC Criteria: June 13, 2007
• First Posted (Estimate): June 14, 2007

Study Record Updates

• Last Update Posted (Estimate): October 17, 2014
• Last Update Submitted That Met QC Criteria: October 15, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: idiopathic thrombocytopenic purpura
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Thrombocytopenia; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Rituximab; Prednisone
• Other Study ID Numbers: CDR0000529883; P30CA015083 (U.S. NIH Grant/Contract); MC0481 (Other Identifier: Mayo Clinic Cancer Center); 2071-04 (Other Identifier: Mayo Clinic IRB); U2985s (Other Identifier: Genentech protocol)