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

Idiopathic Thrombocytopenic Purpura (ITP) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01713738
• Other study ID #: CHB 02-12-160
• Secondary ID: Genentec/IDEC U2
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 18, 2012
• Last updated: November 8, 2012
• Start date: May 2003
• Est. completion date: December 2005

Study information

• Verified date: November 2012
• Source: Neufeld, Ellis J, MD, PhD
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: December 2005
• Est. primary completion date: December 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Months to 18 Years

Eligibility

Inclusion Criteria:

severe, chronic ITP, including refractory; at least 6 months from diagnosis for refractory; at least 12 months from diagnosis for severe; platelet counts <10,000/mm3 twice in past 3 months without bleeding; platelet counts <20,000/mm3 twice in past 3 months with bleeding

Exclusion Criteria:

ever had B or T cell neoplasm; HIV/AIDS; allergy to murine antibodies; treatment with investigational immunosuppressive strategies within past 3 months -

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Idiopathic Thrombocytopenic Purpura (ITP)
• Immune Thrombocytopenic Purpura (ITP)
• Purpura
• Purpura, Thrombocytopenic
• Purpura, Thrombocytopenic, Idiopathic

Intervention

Drug:
• rituximab
infusion of 4 weekly doses of 375 mg/m2 rituximab

Locations

Country	Name	City	State
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Southwestern Medical Center at Dallas	Dallas	Texas
United States	Van Eslander Cancer Center, St. John Hospital	Detroit	Michigan
United States	Baylor College of Medicine	Houston	Texas
United States	UCLA, Mattel Children's Hospital	Los Angeles	California
United States	Weill Medical College at Cornell University	New York	New York
United States	Stanford University School of Medicine	Palo Alto	California
United States	University of California, San Francisco	San Francisco	California

Sponsors (5)

Lead Sponsor	Collaborator
Neufeld, Ellis J, MD, PhD	Biogen, Genentech, Inc., Glaser Pediatric Research Network, Terrana ITP Research Fund

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	platelet levels		9 - 12 weeks after 1st dose of rituximab	No
Primary	hypogammaglobulinemia		over one year	Yes
Secondary	fraction of responsive patients maintaining response over 1 year		week 52	No
Secondary	assessment of need for salvage therapy		first 12 weeks of trial	No
Secondary	rate of early response before day 57		before day 57, and 4 additional weeks	No
Secondary	trend of bleeding scores throughout trial		over one year	No
Secondary	description of health-related quality of life		over one year	No