Clinical trial NCT00486421: Rituximab and Prednisone as First-Line Therapy in Treating Patients With Immune Thrombocytopenic Purpura
Official title: A Pilot Study of Rituximab in Combination With Corticosteroids for the Initial Treatment of Immune Thrombocytopenic Purpura
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Nonneoplastic Condition
Keywords: idiopathic thrombocytopenic purpura
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-06-14
Enrollment: 22
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Failure-free survival at 6 months
timeFrame: 6 months
Secondary outcomes:
measure: Time to platelet recovery
timeFrame: 1 year
measure: Duration of platelet recovery
timeFrame: 1 year
measure: Effect of treatment on prevention of spontaneous bleeding events
timeFrame: 1 year
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Ruben A. Mesa, M.D.
role: STUDY_CHAIR
References: