STAR - Study of TTP and Rituximab, A Randomized Clinical Trial

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-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