Clinical Trial of Rituximab in Children and Adolescents With Chronic Idiopathic Thrombocytopenic Purpura (ITP)
Condition: Idiopathic Thrombocytopenic Purpura (ITP); Immune Thrombocytopenic Purpura (ITP)
MeSH terms: Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of the 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. Response is defined as having a platelet count greater than or equal to 50,000/mL
      on four consecutive weekly measures beginning anytime in weeks 9 - 12.
    

Detailed description: 
      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.
    

Intervention name(s): rituximab
Intervention type(s): Drug
Intervention description(s): infusion of 4 weekly doses of 375 mg/m2 rituximab
Intervention MeSH terms: Rituximab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: ITP; rituximab; bleeding score; platelet count; health-related quality of life; HRQL