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

This study has been completed.
Sponsor:
Collaborators:
Genentech, Inc.
Biogen Idec
Glaser Pediatric Research Network
Terrana ITP Research Fund
Information provided by:
Neufeld, Ellis J, MD, PhD
ClinicalTrials.gov Identifier:
NCT01713738
First received: October 18, 2012
Last updated: November 8, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Idiopathic Thrombocytopenic Purpura (ITP)
Immune Thrombocytopenic Purpura (ITP)
Drug: rituximab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open Label, Phase I/II Trial of Rituximab for Chronic, Severe Idiopathic Thrombocytopenic Purpura (ITP)in Children and Adolescents

Resource links provided by NLM:


Further study details as provided by Neufeld, Ellis J, MD, PhD:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 36
Study Start Date: May 2003
Study Completion Date: December 2005
Primary Completion Date: December 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: rituximab Drug: rituximab
infusion of 4 weekly doses of 375 mg/m2 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.
  Eligibility

Ages Eligible for Study:   18 Months to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 -

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01713738

Locations
United States, California
UCLA, Mattel Children's Hospital
Los Angeles, California, United States, 90095
Stanford University School of Medicine
Palo Alto, California, United States, 94305
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, Michigan
Van Eslander Cancer Center, St. John Hospital
Detroit, Michigan, United States, 48236
United States, New York
Weill Medical College at Cornell University
New York, New York, United States, 10021
United States, Texas
Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75390
Baylor College of Medicine
Houston, Texas, United States, 77030
Sponsors and Collaborators
Neufeld, Ellis J, MD, PhD
Genentech, Inc.
Biogen Idec
Glaser Pediatric Research Network
Terrana ITP Research Fund
Investigators
Principal Investigator: Ellis J Neufeld, MD, PhD Children's Hospital Boston
  More Information

No publications provided

Responsible Party: Ellis J. Neufeld, MD, PhD, Children's Hospital Boston
ClinicalTrials.gov Identifier: NCT01713738     History of Changes
Other Study ID Numbers: CHB 02-12-160, Genentec/IDEC U2591S, Glaser 435
Study First Received: October 18, 2012
Last Updated: November 8, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Neufeld, Ellis J, MD, PhD:
ITP
rituximab
bleeding score
platelet count
health-related quality of life
HRQL

Additional relevant MeSH terms:
Purpura
Purpura, Thrombocytopenic
Purpura, Thrombocytopenic, Idiopathic
Autoimmune Diseases
Blood Coagulation Disorders
Blood Platelet Disorders
Hematologic Diseases
Hemorrhage
Hemorrhagic Disorders
Immune System Diseases
Pathologic Processes
Signs and Symptoms
Skin Manifestations
Thrombocytopenia
Thrombotic Microangiopathies
Rituximab
Antineoplastic Agents
Antirheumatic Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014