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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2009 by University College, London.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
University College, London
ClinicalTrials.gov Identifier:
NCT00937131
First received: July 9, 2009
Last updated: NA
Last verified: July 2009
History: No changes posted
  Purpose

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 Intervention Phase
Thrombotic Thrombocytopenic Purpura (TTP)
Drug: Rituximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

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

Enrollment: 40
Study Start Date: March 2006
Estimated Study Completion Date: June 2010
Estimated Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Rituximab
    Concentrate for solution for infusion, Intravenous use, 375mg/m2, Maximum 8 weekly infusions
    Other Name: Rituximab (MabThera)
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  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: NCT00937131

Locations
United Kingdom
University College London Hospitals
London, United Kingdom, W1
St Bartholomew's Hospital
London, United Kingdom, EC1A 7BE
St Thomas Hosptial
London, United Kingdom, SE1 7EH
Sponsors and Collaborators
University College, London
Investigators
Principal Investigator: Marie A Scully, MBBS, BSc, MRCPath University College London, University College London Hosptials NHS Trust
  More Information

No publications provided by University College, London

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Nadeem Khan, University College London
ClinicalTrials.gov Identifier: NCT00937131     History of Changes
Other Study ID Numbers: BRD/05/011
Study First Received: July 9, 2009
Last Updated: July 9, 2009
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

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

ClinicalTrials.gov processed this record on October 01, 2014