Clinical Trial of Rituximab in Children and Adolescents With Chronic Idiopathic Thrombocytopenic Purpura (ITP)

• platelet levels [ Time Frame: 9 - 12 weeks after 1st dose of rituximab ] [ Designated as safety issue: No ]
  
• hypogammaglobulinemia [ Time Frame: over one year ] [ Designated as safety issue: Yes ]
  

• fraction of responsive patients maintaining response over 1 year [ Time Frame: week 52 ] [ Designated as safety issue: No ]
  
• assessment of need for salvage therapy [ Time Frame: first 12 weeks of trial ] [ Designated as safety issue: No ]
  
• rate of early response before day 57 [ Time Frame: before day 57, and 4 additional weeks ] [ Designated as safety issue: No ]
  
• trend of bleeding scores throughout trial [ Time Frame: over one year ] [ Designated as safety issue: No ]
  
• description of health-related quality of life [ Time Frame: over one year ] [ Designated as safety issue: No ]
  

The purpose of this open label, phase I/II study is to evaluate the safety and efficacy of rituximab in children ages 18 months to 18 years, who have severe, chronic ITP. Eligible patients with either primary or secondary ITP are treated with rituximab once a week for 4 doses, and then followed for up to one year. The primary and secondary objectives for safety and efficacy are as follows:

Primary

1. Efficacy: To evaluate the effectiveness of rituximab in severe or refractory pediatric ITP, with response defined as follows: platelet count greater than or equal to 50,000/mL on four consecutive weekly measures beginning anytime in weeks 9 - 12 (day 57 - day 84), with the first and fourth measure being spaced at least 22 days apart (i.e., once established during the 9 - 12 week timeframe, the response would be defined as beginning at the first one of these measures). All measurements must be independent of supportive care, as follows: 1) no IVIG (intravenous immunoglobulin) administration within 7 days of the first measure or at any time between measures, 2) no initiation of a 4-day corticosteroid "pulse" within 7 days of the first measure or at any time between measures, 3) no RHo (D) immunoglobulin (WinRHo-SDFTM ) administration within 7 days of the first measure or at any time between measures, and 4) no platelet transfusions administered within 7 days of the first measure or at any time between measures.
2. Safety: To obtain further safety information on rituximab in this clinical setting using Genentech standard safety monitoring and SAE reporting. In addition, the frequency of hypogammaglobulinemia will be assessed as the incidence of IgG levels <1/2 the lower limit of normal for age.

Secondary

1. To evaluate the one-year clinical course of severe or refractory ITP patients treated with a single course of rituximab. What fraction of responsive patients maintains this response?
2. To assess the need for salvage therapy (supportive care) in this severely affected group of patients during the clinical trial.
3. To evaluate the rate of "early response," defined as: platelets greater than or equal to 50,000/mL at least one week off rescue therapy, BEFORE day 57, and continuing for four consecutive weeks.
4. To follow the trend of bleeding scores from onset of therapy through the duration of the trial.
5. To assess the incidence of hypogammaglobulinemia requiring intervention (IgG level <1/2 of lower limit of normal for age) in this setting. IVIG 400 mg/kg monthly will be used to treat hypogammaglobulinemia.
6. To describe the health-related quality of life (HRQL) of children with severe or refractory ITP, based on parent report and to assess the impact on the family, using standardized questionnaires. This is a pilot-scale objective.