Clinical trial NCT00531089: Rituximab in Patients With Relapsed or Refractory TTP-HUS
Official title: A Phase II Study Evaluating the Efficacy of Rituximab in the Management of Patients With Relapsed/Refractory Thrombotic Thrombocytopenic Purpura (TTP) - Hemolytic Uremic Syndrome (HUS)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Thrombotic Thrombocytopenic Purpura
Hemolytic Uremic Syndrome
Keywords: TTP
thrombotic thrombocytopenic purpura
HUS
hemolytic uremic syndrome
plasma exchange
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: Canadian Apheresis Group
name: Hoffmann-La Roche
name: McMaster University
First posted: 2007-09-18
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The general objective of this study is to assess the efficacy and safety of Rituximab in the management of patients with refractory or relapsed thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS). There have been several case reports and case series describing the use of Rituximab in patients with TTP-HUS; however its use has not been studied in a large trial. It is hypothesized that Rituximab may ameliorate the severity of certain cases of TTP-HUS by decreasing the number of activity of B-cells which may result in decreased production of the ADAMTS13 protease inhibitor. Patients with TTP-HUS not responding to standard therapy or patients with relapsed disease may have particular benefit. Treatments that decrease the frequency of relapse or shorten the time to remission of TTP-HUS will be of benefit by decreasing the need for blood product support.


Eligibility criteria: Inclusion Criteria:

* any patient 18 years or older diagnosed with relapsed or refractory TTP-HUS requiring therapy

Exclusion Criteria:

* alternate cause of hemolytic microangiopathy (evidence of DIC, malignant hypertension, vasculitis, anti-phospholipid antibody syndrome, post-partum acute renal failure)
* congenital or familial TTP
* TTP occuring post-stem cell, bone marrow, or solid organ transplant
* drug-induced TTP
* pregnancy or breast-feeding
* history of hepatitis B or C infection
* prior rituximab treatment
* active or metastatic cancer
* other causes of thrombocytopenia such as ITP, myelodysplastic syndrome, confirmed or suspected drug-induced thrombocytopenia
* refusal to receive blood products
* hypersensitivity to blood products, plasma products, murine proteins, or any component of the Rituximab formulation
* geographic inaccessibility
* co-morbid illness limiting life expectancy to less than 2 months independent of TTP
* failure to provide written informed consent

Primary outcomes:
measure: The proportion of patients achieving all: (1) platelet count >150x109/L; (2) LDH < 1.5 x normal; (3) no requirement for plasma exchange therapy; (4) asymptomatic.
timeFrame: 8 weeks after initiation of therapy
Secondary outcomes:
measure: proportion of patients with platelet count greater than 150 x 109/L
timeFrame: 8 weeks
measure: proportion of patients with LDH < 1.5 X normal
timeFrame: 8 weeks
measure: proportion of patients with no requirement for plasma exchange therapy
timeFrame: 8 weeks
measure: proportion of patients who are asymptomatic (no new neurological symptoms ans stabilization of previous neurological symptoms
timeFrame: 8 weeks
measure: clinical response (CR, PR, non-response)
timeFrame: 52 weeks
measure: frequency of relapse
timeFrame: 52 weeks
measure: mortality
timeFrame: 52 weeks
measure: changes from baseline in platelet counts, LDH, ADAMTS13 protease level, ADAMTS13 inhibitor level
timeFrame: 8, 12, 24, 52 weeks
measure: toxicity and clinical safety as assessed by monitoring of adverse events, laboratory parameters, vital signs during infusion, and immediate tolerability
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Foothills Medical Centre, Calgary Health REgion Apheresis Service
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: Winnipeg Regional Health Authority, Apheresis Department
state: Manitoba
city: St. John
country: Canada
facility: St. John Regional Hospital
state: New Brunswick
city: Hamilton
country: Canada
facility: Hamilton Health Sciences
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre, Westminister Campus
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital, ABMT/Apheresis Unit
state: Ontario
city: Greenfield Park
country: Canada
facility: Hopital Charles Lemoyne
state: Quebec
city: Montreal
country: Canada
facility: Hopital du Sacre-Coeur de Montreal
state: Quebec
city: Saskatoon
country: Canada
facility: St. Paul's Hospital Apheresis Unit
state: Saskatchewan
Study officials:
affiliation: Hamilton Health Sciences Corporation
name: Kathryn E Webert, E
role: PRINCIPAL_INVESTIGATOR
affiliation: Hamilton Health Sciences Corporation
name: Ronan Foley, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Canadian Apheresis Group
name: Gail Rock, MD
role: STUDY_DIRECTOR
affiliation: University of Western Ontario/London Health Sciences
name: William Clark, MD
role: STUDY_DIRECTOR
affiliation: University of Toronto
name: David Barth, MD
role: STUDY_DIRECTOR
References: