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

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

Sponsors

Lead Sponsor: Hamilton Health Sciences Corporation

Collaborator: Hoffmann-La Roche

Source McMaster University
Brief 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).

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.

Overall Status Completed
Start Date September 2006
Completion Date June 2011
Primary Completion Date December 2010
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Feasibility of recruitment 3 years
Degree of adherence to the study protocol 3 years
Event free survival in controls 6 months
Bleeding 6 months
rescue therapy 6 months
Secondary Outcome
Measure Time Frame
Platelet count response 6 months
Quality of life 6 months
Circulating CD-20 positive lymphocytes 6 months
Platelet associated IgG 6 months
Enrollment 60
Condition
Intervention

Intervention Type: Drug

Intervention Name: Rituximab

Description: 375mg/m2 per week for 4 consecutive weeks

Arm Group Label: A

Other Name: Rituxan, Mabthera

Intervention Type: Drug

Intervention Name: Placebo

Description: Saline IV placebo once per week for 4 consecutive weeks

Arm Group Label: B

Eligibility

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: 80 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Donald M Arnold, MD Principal Investigator McMaster University
Location
Facility:
St. Paul's Hospital | Vancouver, British Columbia, V6Z 2A5, Canada
Queen Elizabeth II Health Sciences Centre | Halifax, Nova Scotia, B3H 1V7, Canada
McMaster Univerisity | Hamilton, Ontario, L8N3Z5, Canada
Grand River Regional Cancer Centre | Kitchener, Ontario, N2G 1G3, Canada
London Health Sciences Centre | London, Ontario, N6A 4S2, Canada
Ottawa Health Research Institute | Ottawa, Ontario, K1H 8L6, Canada
University Health Network | Toronto, Ontario, M5G 2C4, Canada
Location Countries

Canada

Verification Date

June 2012

Responsible Party

Type: Principal Investigator

Investigator Affiliation: McMaster University

Investigator Full Name: Donald Arnold

Investigator Title: MD

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: A

Type: Active Comparator

Description: Rituximab

Label: B

Type: Placebo Comparator

Description: Saline placebo iv infusion

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Prevention

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov