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The Use of Rituximab in Acute Thrombotic Thrombocytopenic Purpura (TTP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. 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
Information provided by:
University College, London

Brief Summary:

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Intervention Details:
  • Drug: Rituximab
    Concentrate for solution for infusion, Intravenous use, 375mg/m2, Maximum 8 weekly infusions
    Other Name: Rituximab (MabThera)

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Improved mortality ot TTP patients [ Time Frame: 3 months ]
  2. Safety and toxicity of Rituximab in conjunction with standard therapy for acute TTP [ Time Frame: 3 months ]
  3. Effect of Rituximab on B lymphocyte function [ Time Frame: One year ]
  4. Effect of Rituximab on ADAMTS 13 activity and antibody production and time to relapse [ Time Frame: One year ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients > 18 years and < 65 years who present with an acute episode of TTP
  • Evidence of microangiopathic haemolytic anaemia
  • Thrombocytopenia with a normal clotting screen
  • Raised Lactate Dehydrogenase (one and a half time above upper normal)
  • Patients without neurological dysfunction able to give informed consent
  • Patients of reproductive age (must avoid pregnancy for 12 months and/or normalised B cell function after receiving Rituximab. Oestrogen containing oral contraceptive pills and the morning after pills should be avoided in female TTP patients)
  • Patients with an acute deterioration in neurological function which may include encephalopathy, such as altered personality, problems with short term memory and coma can be included when consent has been given by next of kin or from the appropriate legal representative.

Exclusion Criteria:

  • All female subjects who are knowingly pregnant or breast feeding or do not use an adequate form of contraception (the effect on the foetus and newborn have not yet been fully established so Rituximab should be avoided in these groups. Male patients receiving Rituximab should ensure adequate contraception for 12 months following treatment).
  • Patients who are HIV positive (which does not appear to be antibody mediated, would be unlikely to benefit from Rituximab)
  • Patients with childhood TTP
  • Patients who have Haemolytic Uraemic Syndrome (HUS) (which is not associated with reduced ADAMTS 13 levels)
  • Patients who are post bone marrow transplant - either autologous or allogeneic
  • Patients wiht a medical or long term psychiatric condition which, in the opinion of the investigator, contraindicates the patients' participation into the trial
  • Previous or concurrent malignancies at other sites, with exception of appropriately treated localized epithelial or cervical cancer. Patients with a history of cured tumours may be entered (> 5 years).

Information from the National Library of Medicine

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 identifier (NCT number): NCT00937131

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United Kingdom
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
Sponsors and Collaborators
University College, London
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Principal Investigator: Marie A Scully, MBBS, BSc, MRCPath University College London, University College London Hosptials NHS Trust
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Nadeem Khan, University College London Identifier: NCT00937131    
Other Study ID Numbers: BRD/05/011
First Posted: July 10, 2009    Key Record Dates
Last Update Posted: July 10, 2009
Last Verified: July 2009
Additional relevant MeSH terms:
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Purpura, Thrombocytopenic
Purpura, Thrombotic Thrombocytopenic
Blood Coagulation Disorders
Hematologic Diseases
Pathologic Processes
Skin Manifestations
Thrombotic Microangiopathies
Blood Platelet Disorders
Immune System Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents