The Use of Rituximab in Acute Thrombotic Thrombocytopenic Purpura (TTP)
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|ClinicalTrials.gov Identifier: NCT00937131|
Recruitment Status : Unknown
Verified July 2009 by University College, London.
Recruitment status was: Active, not recruiting
First Posted : July 10, 2009
Last Update Posted : July 10, 2009
TTP is a rare and serious blood disorder, characterized by the formation of small clots (micro thrombi) within the circulation and can be fatal. The formation of blood clots occurs primarily in the smaller blood vessels, the arterioles and capillaries, associated with multisystem organ involvement, especially the brain and kidneys. TTP has an incidence of approximately 1-3 people/million of the population/year.
TTP is due to a decrease in an enzyme, ADAMTS 13 that is released by cells lining blood vessels (endothelial cells). ADAMTS 13 'cleaves' or breaks down very large von Willebrand Factor (vWF) strands. vWF is used in blood clotting. Deficiency or inhibition of the enzyme, results in release of the ultra large vWF into the circulation. Platelets bind to these ultra large vWF multimers, promoting blood clot formation and platelet consumption (thrombocytopenia). In more then 70% of TTP cases no precipitating cause can be found and the majority of these patients have antibodies against ADAMTS 13. Plasma Exchange (PEX) was introduced in the management of TTP in 1977 and the mortality of TTP patients has since decreased from approximately 90% to 15-20%. PEX is essential in TTP treatment as plasma contains the missing enzyme ADAMTS 13.
Rituximab (licensed and internationally used monoclonal antibody) selectively acts on white blood cells known as B-lymphocytes or B cells that produce the antibody to ADAMTS 13. By inhibiting ADAMTS 13 antibody production, ADAMTS 13 activity increases, resulting in remission. Rituximab has been used in our institutions in patients with acute TTP that are refractory to standard treatment - PEX. The resulting remission has been dramatic, with a non-toxic side effect profile and no patients to date has relapsed (longest follow-up 19 months) following Rituximab therapy. Therefore, we plan to use Rituximab with PEX in patients who present with acute TTP.
|Condition or disease||Intervention/treatment||Phase|
|Thrombotic Thrombocytopenic Purpura (TTP)||Drug: Rituximab||Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Study to Assess the Safety, Efficacy and Tolerability of Rituximab (Mabthera) in Combination With Plasma Exchange (PEX) in Patients With Acute Thrombotic Thrombocytopenic Purpura (TTP)|
|Study Start Date :||March 2006|
|Estimated Primary Completion Date :||June 2010|
|Estimated Study Completion Date :||June 2010|
- Drug: Rituximab
Concentrate for solution for infusion, Intravenous use, 375mg/m2, Maximum 8 weekly infusionsOther Name: Rituximab (MabThera)
- The primary objective of this study is to investigate whether Rituximab and PEX decreases the time to remission of TTP patients. [ Time Frame: One year ]
- Improved mortality ot TTP patients [ Time Frame: 3 months ]
- Safety and toxicity of Rituximab in conjunction with standard therapy for acute TTP [ Time Frame: 3 months ]
- Effect of Rituximab on B lymphocyte function [ Time Frame: One year ]
- Effect of Rituximab on ADAMTS 13 activity and antibody production and time to relapse [ Time Frame: One year ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00937131
|St Bartholomew's Hospital|
|London, United Kingdom, EC1A 7BE|
|St Thomas Hosptial|
|London, United Kingdom, SE1 7EH|
|University College London Hospitals|
|London, United Kingdom, W1|
|Principal Investigator:||Marie A Scully, MBBS, BSc, MRCPath||University College London, University College London Hosptials NHS Trust|