Trial Information

Open Label, Phase I/II Trial of Rituximab for Chronic, Severe Idiopathic Thrombocytopenic Purpura (ITP)in Children and Adolescents

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.