Pilot Study of Rituximab for the Treatment of Acute Immune Thrombocytopenic Purpura (ITP)

Purpura, Thrombocytopenic, Idiopathic Clinical Trial

Official title:

A Randomized, Double Blind, Placebo Controlled Pilot Trial of Rituximab for Non-splenectomized Adults With Acute Immune Thrombocytopenic Purpura Receiving Standard Treatment (R-ITP)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00372892
• Other study ID #: 06-105
• Secondary ID: HC-104634
• Status: Completed
• Phase: Phase 2
• First received: September 6, 2006
• Last updated: June 6, 2012
• Start date: September 2006
• Est. completion date: June 2011

Study information

• Verified date: June 2012
• Source: McMaster University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the feasibility of a randomized, double blind, placebo controlled trial of add-on rituximab for non-splenectomized adults with acute immune thrombocytopenic purpura (ITP).

Description:

Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by severe thrombocytopenia and bleeding. With current standard therapies, adult-onset ITP tends to recur thus exposing patients to prolonged risks of hemorrhage and toxicities of standard treatments. Rituximab, a chimeric anti-CD20 monoclonal antibody, has been shown to be effectively raise the platelet count in some patients with ITP and there is clinical and biological evidence to suggest that, if given early, rituximab may prevent ITP relapses.

We have designed a randomized, double blind, placebo controlled pilot trial of rituximab for the treatment of non-splenectomized adults with acute ITP who are receiving standard treatments. The primary objectives of this trial are to determine the feasibility of recruitment, randomization and blinding; the safety of rituximab in ITP; and the event rate in the control group which will be used to calculate the sample size for a larger trial. Secondary objectives are to determine rates of 6-month event free survival where an event is defined as any of: a platelet count <50; the need for rescue treatment; or significant bleeding. Data from this pilot trial will inform the design of a larger phase III trial.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: June 2011
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Non-splenectomized patients with acute ITP, where "acute ITP" is defined as a platelet count below 30 at the time that standard treatment was recommended by a physician and for which no treatment had been received for the preceding 30 days.

• Must be receiving standard ITP treatment.

Exclusion Criteria:

• Cardiac arrhythmia.

• Uncontrolled hypertension or inability to hold antihypertensive medications for 12 hours prior to and throughout study drug infusions.

• Known coronary artery disease, angina pectoris or myocardial infarction within the last year.

• Significant pulmonary disease within the last year.

• Stroke, transient ischemic attack or venous thrombosis within the last year.

• Secondary causes of thrombocytopenia (splenomegaly [palpable spleen or radiologically confirmed >14 cm], drug-induced thrombocytopenia, hereditary thrombocytopenia, microangiopathic hemolytic anemia, myelodysplastic syndrome).

• Chronic lymphocytic leukemia or lymphoma.

• Active or metastatic cancer.

• History of hepatitis B or C or HIV.

• Active infection in the 4 weeks before randomization.

• Inherited coagulation factor deficiency.

• Aspirin, aspirin-containing compounds, salicylates, non-steroidal anti-inflammatory medications (NSAIDS) medications, clopidogrel or ticlopidine in the 7 days preceding study drug infusions; vitamin K antagonists (warfarin) in the 3 days preceding study drug infusions; unfractionated heparin or low molecular weight heparin in the 24 hours preceding study drug infusions.

• Elevated INR or prolonged PTT; LDH, serum creatinine, liver function tests (AST/SGOT, ALT/SGPT, alkaline phosphatase, total bilirubin) increased more than 1.5 times upper limit of normal.

• Prior rituximab treatment.

• Unable to schedule 4 weekly study infusions.

• Pregnancy or breastfeeding.

• Known sensitivity to murine proteins, Chinese Hamster Ovary (CHO) cell proteins or to any component of rituximab.

• Participation in another clinical trial.

• Geographic inaccessibility.

• Failure to provide written informed consent.

• Any additional laboratory test result, health related illness or other diagnosis which, in the opinion of the treating physician, may put the subject's health or safety at risk.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Purpura
• Purpura, Thrombocytopenic
• Purpura, Thrombocytopenic, Idiopathic

Intervention

Drug:
• Rituximab
375mg/m2 per week for 4 consecutive weeks
• Placebo
Saline IV placebo once per week for 4 consecutive weeks

Locations

Country	Name	City	State
Canada	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	McMaster Univerisity	Hamilton	Ontario
Canada	Grand River Regional Cancer Centre	Kitchener	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	Ottawa Health Research Institute	Ottawa	Ontario
Canada	University Health Network	Toronto	Ontario
Canada	St. Paul's Hospital	Vancouver	British Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Hamilton Health Sciences Corporation	Hoffmann-La Roche

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility of recruitment		3 years	No
Primary	Degree of adherence to the study protocol		3 years	No
Primary	Event free survival in controls		6 months	No
Primary	Bleeding		6 months	Yes
Primary	rescue therapy		6 months	Yes
Secondary	Platelet count response		6 months	No
Secondary	Quality of life		6 months	No
Secondary	Circulating CD-20 positive lymphocytes		6 months	No
Secondary	Platelet associated IgG		6 months	No