Clinical trial NCT01713738: Clinical Trial of Rituximab in Children and Adolescents With Chronic Idiopathic Thrombocytopenic Purpura (ITP)
Official title: Open Label, Phase I/II Trial of Rituximab for Chronic, Severe Idiopathic Thrombocytopenic Purpura (ITP)in Children and Adolescents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Idiopathic Thrombocytopenic Purpura (ITP)
Immune Thrombocytopenic Purpura (ITP)
Keywords: ITP
rituximab
bleeding score
platelet count
health-related quality of life
HRQL
Lead sponsor: Neufeld, Ellis J, MD, PhD
Sponsor class: INDIV
Collaborators: name: Genentech, Inc.
name: Biogen
name: Glaser Pediatric Research Network
name: Terrana ITP Research Fund
First posted: 2012-10-25
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Eligibility 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 -

Primary outcomes:
measure: platelet levels
timeFrame: 9 - 12 weeks after 1st dose of rituximab
measure: hypogammaglobulinemia
timeFrame: over one year
Secondary outcomes:
measure: fraction of responsive patients maintaining response over 1 year
timeFrame: week 52
measure: assessment of need for salvage therapy
timeFrame: first 12 weeks of trial
measure: rate of early response before day 57
timeFrame: before day 57, and 4 additional weeks
measure: trend of bleeding scores throughout trial
timeFrame: over one year
measure: description of health-related quality of life
timeFrame: over one year
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA, Mattel Children's Hospital
state: California
city: Palo Alto
country: United States
facility: Stanford University School of Medicine
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Detroit
country: United States
facility: Van Eslander Cancer Center, St. John Hospital
state: Michigan
city: New York
country: United States
facility: Weill Medical College at Cornell University
state: New York
city: Dallas
country: United States
facility: Southwestern Medical Center at Dallas
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
affiliation: Boston Children's Hospital
name: Ellis J Neufeld, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: