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

NCT00937131 | Completed Phase 2

• 1 other identifier: BRD/05/011
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

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.

Conditions

Thrombotic Thrombocytopenic Purpura (TTP)

Outcome Measures

Primary Outcomes (1)

• The primary objective of this study is to investigate whether Rituximab and PEX decreases the time to remission of TTP patients.

  One year

Secondary Outcomes (4)

• Improved mortality ot TTP patients

  3 months

• Safety and toxicity of Rituximab in conjunction with standard therapy for acute TTP

  3 months

• Effect of Rituximab on B lymphocyte function

  One year

• Effect of Rituximab on ADAMTS 13 activity and antibody production and time to relapse

  One year

Study Arms (1)

no comparator

NO INTERVENTION

Drug: Rituximab

Interventions

Rituximab DRUG

Concentrate for solution for infusion, Intravenous use, 375mg/m2, Maximum 8 weekly infusions

Also known as: Rituximab (MabThera)

no comparator

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University College, London: lead

Study Sites (3)

St Bartholomew's Hospital

London, EC1A 7BE, United Kingdom

Location

St Thomas Hosptial

London, SE1 7EH, United Kingdom

Location

University College London Hospitals

London, W1, United Kingdom

Location

Related Publications (1)

• Scully M, McDonald V, Cavenagh J, Hunt BJ, Longair I, Cohen H, Machin SJ. A phase 2 study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura. Blood. 2011 Aug 18;118(7):1746-53. doi: 10.1182/blood-2011-03-341131. Epub 2011 Jun 2.

  PMID: 21636861 DERIVED

MeSH Terms

Conditions

Purpura, Thrombotic Thrombocytopenic

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Thrombophilia; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Marie A Scully, MBBS, BSc, MRCPath

  University College London, University College London Hosptials NHS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2009
• First Posted: July 10, 2009
• Study Start: March 1, 2006
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: May 16, 2023

Record last verified: 2023-05

Locations

GB (3)