A Trial to Treat Patients With ITP Who Do Not Achieve a Durable Response to Rituxan Alone

Inclusion Criteria:

Patients will be eligible to participate in the study if they:

• Have chronic ITP19 (> 6 months duration).
• Have received Rituximab a minimum of 3 months prior to entry.
• Have received no more than 2 courses of Rituximab at standard dose separated by a minimum of 12 weeks.
• Have not achieved a durable response to Rituximab, with platelet counts < 30,000/ml when not supported by other treatment.
• Have a platelet count of < 30,000/ul on two separate occasions 1-2 weeks apart within the past month prior to the inclusion.
• Are age ≥ 12 years old.
• Had a splenectomy at least 60 days prior to study entry, or a contraindication to splenectomy.
• Give written informed consent.
• Use an effective means of contraception during treatment and for six months after completion of treatment.
• Have negative serum pregnancy test, for all women who are able to have children, within 14 days prior to study entry.

Exclusion Criteria:

Male and female subjects will be ineligible to participate if they:

• Received prior treatment with cyclophosphamide within the last 3 months.
• Received prior treatment with > 4 infusions of vinca alkaloids within the 6 months.
• Had previous or concomitant malignancy other than basal cell or squamous cell carcinoma of the skin, carcinoma-in-situ of the cervix, or other malignancy for which the patient had not been disease-free for at least 5 years.
• Have an HIV infection.
• Have hepatitis Bs antigen positivity or active hepatitis C infection
• Have an absolute neutrophil count < 1.000/mm3 at study entry (unless related to autoimmune neutropenia).
• Have a Hemoglobin level < 10 g/dl other than caused by thalassemia trait, iron deficiency or autoimmune hemolytic anemia (patients with Evan's syndrome will not be excluded).
• Have an impaired renal function as indicated by a serum creatinine level > 2.0 mg/dL.
• Have an inadequate liver function as indicated by a total bilirubin level > 2.0 mg/dL and/or an AST or ALT level > 3x upper limit of normal.
• Have active infection requiring antibiotic therapy within 7 days prior to study entry.
• Are pregnant or lactating women, or plan to become pregnant or impregnated within 12 months of receiving study drug.
• Have had a prior severe reaction to Rituximab, leading to discontinuation of treatment.
• Have a New York Heart Classification III or IV heart disease.
• Have a history of severe psychiatric disorder or are unable to comply with study and follow-up procedures.