Evaluating the Effectiveness of Adding Rituximab to Standard Treatment for Thrombotic Thrombocytopenic Purpura (TTP)

• Status: Terminated
• Trial end date: 2010-02-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: HealthCore-NERI; New England Research Institutes
• Collaborators: Genentech, Inc.; National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Rituximab

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