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

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

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.

Study Overview

• Status: Completed
• Conditions: Immune Thrombocytopenic Purpura (ITP); Idiopathic Thrombocytopenic Purpura (ITP)
• Intervention / Treatment: Drug: rituximab

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA, Mattel Children's Hospital
    • Palo Alto, California, United States, 94305
      • Stanford University School of Medicine
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Children's Hospital Boston
  • Michigan
    • Detroit, Michigan, United States, 48236
      • Van Eslander Cancer Center, St. John Hospital
  • New York
    • New York, New York, United States, 10021
      • Weill Medical College at Cornell University
  • Texas
    • Dallas, Texas, United States, 75390
      • Southwestern Medical Center at Dallas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: rituximab	Drug: rituximab; infusion of 4 weekly doses of 375 mg/m2 rituximab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
platelet levels	9 - 12 weeks after 1st dose of rituximab
hypogammaglobulinemia	over one year

Secondary Outcome Measures

Outcome Measure	Time Frame
fraction of responsive patients maintaining response over 1 year	week 52
assessment of need for salvage therapy	first 12 weeks of trial
rate of early response before day 57	before day 57, and 4 additional weeks
trend of bleeding scores throughout trial	over one year
description of health-related quality of life	over one year

Collaborators and Investigators

• Sponsor: Neufeld, Ellis J, MD, PhD
• Collaborators: Genentech, Inc.; Biogen; Glaser Pediatric Research Network; Terrana ITP Research Fund

Study record dates

Study Major Dates

• Study Start: May 1, 2003
• Primary Completion (ACTUAL): December 1, 2005
• Study Completion (ACTUAL): December 1, 2005

Study Registration Dates

• First Submitted: October 18, 2012
• First Submitted That Met QC Criteria: October 22, 2012
• First Posted (ESTIMATE): October 25, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): November 9, 2012
• Last Update Submitted That Met QC Criteria: November 8, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: rituximab; health-related quality of life; ITP; HRQL; platelet count; bleeding score
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Thrombocytopenia; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: CHB 02-12-160; Genentec/IDEC U2591S; Glaser 435