NIPH Clinical Trials Search

Investigator Initiated Clinical Trial of Rituximab for Thrombotic Thrombocytopenic Purpura

Basic Information

Recruitment status	COMPLETED
Health condition(s) or Problem(s) studied	Thrombotic Thrombocytopenic Purpura
Date of first enrollment	20/01/2014
Target sample size	8
Countries of recruitment	Japan
Study type	Interventional
Intervention(s)	Intervention type:DRUG Name of intervention:Rituximab Dose form / Japanese Medical Device Nomenclature:INJECTION Route of administration / Site of application:INTRAVENOUS DRIP Dose per administration:375 mg/m2 mg/m2 Dosing frequency / Frequency of use:QW 4 Planned duration of intervention:4 weeks Intended dose regimen:1st cycle Initiate infusion at a rate of 50 mg/hr. In the absence of adverse events such as allergic reaction or infusion reaction, increase infusion rate by 50 mg/hr increments every 30 minutes, to a maximum of 400 mg/hr. Subsequent cycles If patients did not experience or experience grade 2 or less severe adverse events such as allergic reaction or infusion reaction during previous cycles, initiate infusion at a rate of 100 mg/hr and increase infusion rate by 100 mg/hr increments every 30 minutes, to a maximum of 400 mg/hr. If patients experience grade 3 or more severe adverse events such as allergic reaction or infusion reaction during previous cycles, initiate infusion at a rate of 50 mg/hr and increase infusion rate by 50 mg/hr increments every 30 minutes, to a maximum of 400 mg/hr. detailes of teratment arms: Comparative intervention name: Dose form / Japanese Medical Device Nomenclature: Route of administration / Site of application: Dose per administration: Dosing frequency / Frequency of use: Planned duration of intervention: Intended dose regimen:

Outcome(s)

Primary Outcome

Response rate at 4 weeks. Response is defined by fulfilling all the conditions below. 1) Normalization of platelet count 2) cessation of plasma exchange 3) Improvement of clinical symptoms

Secondary Outcome

1) Peripheral blood B-cell count (CD20 positive cell, CD19 positive cell), peripheral blood T-cell count (CD3 positive cell) 2) Changes of platelet count from base line. 3) Normalization of platelet count: the rate of patients who achieved plate count of >=150,000/microL. 4) Cessation of plasma exchange: the rate of patients who achieved plate count of >=150,000/microL for 2 consecutive days and cessation of plasma exchange. 5) Improvement of clinical symptoms: improvement of anemia (Normalization of hemoglobin level or increase of hemoglobin level by 2 g/dL or more), Neuropsychiatric symptoms (Improvement of sum of GCS from base line).

Key inclusion & exclusion criteria

Age minimum	>= 20age old
Age maximum	<= 79age old
Gender	Both
Include criteria	Tentative registration 1)Definitive or suspected case of acquired TTP according to the Provisional Diagnostic Guideline of TTP of Study Group for Coagulation Disorders (MHLW). -Definitive diagnosis: ADAMTS13 activity <5% and ADAMTS13 inhibitor positive, or presence of all of the 5 clinical symptoms(*) regardless of ADAMTS13 activity. Suspected diagnosis: presence of thrombocytopenia and microangiopathic hemolytic anemia regardless of ADAMTS13 activity. * thrombocytopenia, microangiopathic hemolytic anemia, renal insufficiency, fever, fluctuating levels of neuropsychiatric symptoms. 2) 20 to 79 years old at the time of informed consent. 3) Written informed consent from the subject or legally acceptable representative Registration 1) Patients with refractory or relapsed TTP who fulfill the criteria below. -refractory TTP: fulfill one of the following conditions i) Platelet count <50,000/microL after 5 procedures of plasma exchange. ii) ADAMTS13 inhibitor level of 2 bethesda unit (BU)/mL or more at the time of tentative registration. -relapsed TTP: relapse after at least 30 days from the previous episode.
Exclude criteria	Tentative registration 1) Secondary TTP associated with drug, hematopoietic stem cell transplantation, solid organ transplantation, collagen disease, malignancy, or pregnancy. 2) Congenital TTP (Upshaw-Shulman Syndrome) due to ADMTS 13 deficiency. 3) Presence of malignancy. 4) Severe hematological, neuropsychiatric, hepatic, pulmonary, endocrinological, immunological, or gastrointestinal conditions not related to TTP. 5) Previous exposure to rituximab. 6) Male patient who is not able to consent contraception during study period. 7) Female patient who is pregnant, lactating, or suspected of pregnancy. Female patient who wish to pregnant during study period. 8) Pariticipation in another registration clinical trial and administration of investigational drug during 12 weeks before informed consent. 9) Patients inadequate as the subject of the study judged by investigators. Registration 1) Known HIV seropositive status. 2) Positive status of HBs antigen, HBs antibody, HBc antibody, or HCV antibody except for HBV seropositivity due to vaccination.