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

This study has been completed.
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
Donald Arnold, McMaster University
ClinicalTrials.gov Identifier:
NCT00372892
First received: September 6, 2006
Last updated: June 6, 2012
Last verified: June 2012
  Purpose

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).


Condition Intervention Phase
Purpura, Thrombocytopenic, Idiopathic
Drug: Rituximab
Drug: Placebo
Phase 2

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

Resource links provided by NLM:


Further study details as provided by McMaster University:

Primary Outcome Measures:
  • Feasibility of recruitment [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Degree of adherence to the study protocol [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Event free survival in controls [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Bleeding [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • rescue therapy [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Platelet count response [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Quality of life [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Circulating CD-20 positive lymphocytes [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Platelet associated IgG [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: September 2006
Study Completion Date: June 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A
Rituximab
Drug: Rituximab
375mg/m2 per week for 4 consecutive weeks
Other Name: Rituxan, Mabthera
Placebo Comparator: B
Saline placebo iv infusion
Drug: Placebo
Saline IV placebo once per week for 4 consecutive weeks

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00372892

Locations
Canada, British Columbia
St. Paul's Hospital
Vancouver, British Columbia, Canada, V6Z 2A5
Canada, Nova Scotia
Queen Elizabeth II Health Sciences Centre
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
McMaster Univerisity
Hamilton, Ontario, Canada, L8N3Z5
Grand River Regional Cancer Centre
Kitchener, Ontario, Canada, N2G 1G3
London Health Sciences Centre
London, Ontario, Canada, N6A 4S2
Ottawa Health Research Institute
Ottawa, Ontario, Canada, K1H 8L6
University Health Network
Toronto, Ontario, Canada, M5G 2C4
Sponsors and Collaborators
Hamilton Health Sciences Corporation
Hoffmann-La Roche
Investigators
Principal Investigator: Donald M Arnold, MD McMaster University
  More Information

No publications provided by McMaster University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Donald Arnold, MD, McMaster University
ClinicalTrials.gov Identifier: NCT00372892     History of Changes
Other Study ID Numbers: 06-105, HC-104634
Study First Received: September 6, 2006
Last Updated: June 6, 2012
Health Authority: Canada: Health Canada

Keywords provided by McMaster University:
Idiopathic Thrombocytopenic Purpura
Rituximab
Feasibility study

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

ClinicalTrials.gov processed this record on August 28, 2014