Evaluating the Effectiveness of Adding Rituximab to Standard Treatment for Thrombotic Thrombocytopenic Purpura (TTP)
Condition: Thrombotic Thrombocytopenic Purpura
MeSH terms: Purpura; Purpura, Thrombocytopenic; Purpura, Thrombotic Thrombocytopenic
Intervention: Rituximab; Plasma exchange; Corticosteroids
Intervention description: Dose of 375 mg/m2, given intravenously, repeated at 1-week intervals for a total of four doses; Target volume of 1.25 plasma volume replacement; fresh frozen plasma (FFP) is the required replacement fluid; provided daily until platelet counts are normal and signs of tissue damage have improved.; 1 mg/kg of prednisone (or equivalent) each day until plasma exchange is stopped
Intervention MeSH terms: Rituximab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: TTP; Rituximab; Plasma Exchange

Summary:

      Thrombotic thrombocytopenic purpura (TTP) is a rare disorder that causes blood clots to form
      in blood vessels. The main treatment for TTP is plasma exchange, in which affected patients
      receive transfusions of plasma, the liquid part of blood, from healthy donors. This study
      will examine the effectiveness of an antibody, rituximab, in combination with plasma
      exchange, at improving the immune response in people with TTP and decreasing the recurrence
      of TTP.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Differential or admission diagnosis of TTP-like syndrome, defined as the following:

               1. Platelet count of less than 80,000/µL for newly diagnosed patients and less than
                  120,000/µL for relapsed patients

               2. Microangiopathic hemolytic anemia (MHA) with red blood cell fragmentation

               3. Lactate dehydrogenase (LDH) level greater than two times the upper limit of
                  normal for newly diagnosed patients and greater than the upper limit of normal
                  for relapsed patients

          -  Receiving or will receive treatment for TTP with plasma exchange

          -  Has not started the sixth plasma exchange in the current TTP episode

        Exclusion Criteria:

          -  Treated for TTP in the 2 months before study entry

          -  Previously enrolled in this study

          -  Severe active infection indicated by sepsis (requirement for pressors with or without
             positive blood cultures) or clinical evidence of enteric infection with E. coli 0157
             or related organism

          -  Currently under treatment for cancer or has a current diagnosis of cancer (other than
             localized skin carcinoma)

          -  Microangiopathic hemolytic anemia due to a mechanical heart valve

          -  Severe high blood pressure, as defined by systolic blood pressure of greater than 180
             and diastolic blood pressure of greater than 120, or papilledema

          -  Has ever had an organ or stem cell transplant

          -  Has received calcineurin inhibitors (e.g., sirolimus, tacrolimus, cyclosporin A) in
             the 6 months before TTP diagnosis

          -  Diagnosis of disseminated intravascular coagulation (DIC), defined as the following:

               1. International normalized ratio (INR) level greater than 2.0 (unrelated to
                  anticoagulation, unresponsive to vitamin K administration) OR

               2. Fibrinogen less than 100 mg/dL

          -  Pregnant

          -  Requires ventilator assistance or intravenous pressors for treatment of TTP. If no
             longer required prior to study entry, patient is eligible for the study.

          -  Known congenital TTP or family history of TTP

          -  Established diagnosis of lupus, and/or actively treated for lupus in the 60 days
             before study entry. In addition, people with two or more of the following systemic
             lupus erythematosus (SLE) clinical criteria in the 60 days before study entry will be
             excluded:

               1. Characteristic skin rash, either malar or photosensitive

               2. Symmetric polyarthritis

               3. Serositis, either pleurisy or pericarditis

          -  Previously received rituximab

          -  Has taken the following drugs known to be associated with TTP-like syndrome in the 3
             months before study entry: clopidogrel (Plavix), ticlopidine (Ticlid), or quinine

          -  Will receive more than 1.5 plasma volumes per day after study entry

          -  HIV history or positive serology

          -  History of hepatitis B or positive serology for HBsAg or Anti-hepatitis B core antigen
             (Anti-HBc)

          -  History of hepatitis C

          -  Known persistent or unexplained platelet count below 150,000/µL in the 3 months before
             current TTP episode

          -  Known hypersensitivities or allergies to murine and/or humanized antibodies

          -  Currently participating in trials of investigational therapies or devices (other than
             investigational central catheters)

          -  Has ever had a diagnosis of ventricular tachycardia

          -  Acute transmural heart attack during the current hospital admission