Low Dose Rituximab in Thrombotic Thrombocytopenic Purpura
Low Dose Rituximab in Thrombotic Thrombocytopenic Purpura
Thrombotic thrombocytopenic purpura (TTP) is a disease characterized by small blood clots
 throughout the body that can damage major organs and cause death. TTP is treated with plasma
 exchange (also called "plasmapheresis"). Patients who do not respond initially to plasma
 exchange often are helped by later treatment with rituximab. The purpose of this study is to
 see whether combining low doses of rituximab with plasma exchange will help patients get
 better sooner and reduce the chance of getting TTP again.
This is a pilot safety/efficacy study of adjuvant low dose rituximab (100 mg/week x 4 doses)
 plus standard plasma exchange and corticosteroids for the treatment of thrombotic
 thrombocytopenic purpura (TTP) with severe ADAMTS13 deficiency. Results for study subjects
 will be compared to historical controls treated initially with plasma exchange and
 corticosteroids. This study proposes to test the hypothesis that adjuvant low dose rituximab
 may decrease the incidence of a composite primary endpoint (exacerbations or refractory
 disease) in acquired TTP with severe ADAMTS13 deficiency. A novel ADAMTS13 assay will be used
 to identify patients with TTP and severe ADAMTS13 deficiency for enrollment, and to assess
 the utility of ADAMST13 as a biomarker for response to therapy and prognosis.
Inclusion Criteria:

 1. Age 18 or greater

 2. Diagnosis of suspected thrombotic thrombocytopenic purpura (TTP)

 1. Platelet count of < 80,000 for newly diagnosed patients and < 120,000 for
 relapsed patients

 2. Microangiopathic hemolytic anemia with RBC fragmentation

 3. LDH >1 x ULN

 3. Subjects who will receive treatment for TTP with plasma exchange

 4. Subjects who have not started the 5th plasma exchange

 5. Plasma ADAMTS13 activity <10%

 Exclusion Criteria:

 1. Treatment for TTP within the past 2 months

 2. Severe active infection indicated by sepsis (requirement for pressors with or without
 positive blood cultures) or clinical evidence of enteric infection with E. coli
 O157:H7 or related organism

 3. Currently under treatment for cancer (subjects with localized skin carcinoma will be
 accepted)

 4. Microangiopathic hemolytic anemia due to a mechanical heart valve

 5. Severe hypertension, as defined by systolic BP >180 AND diastolic BP >120, or
 papilledema

 6. Organ or stem cell transplant

 7. Use of calcineurin inhibitors (sirolimus, tacrolimus, cyclosporin A) within 6 months
 prior to diagnosis of TTP

 8. Disseminated intravascular coagulation as defined by:

 a. INR >2.0 (unrelated to anticoagulation, unresponsive to Vitamin K) or b. Fibrinogen
 <100 mg/dl

 9. Pregnancy

 10. Known congenital TTP.

 11. Rituximab within the previous year.

 12. HIV history or positive serology

 13. History of hepatitis B or positive serology for HBsAg or Anti-HBc

 14. Persistent or unexplained platelet count below 150,000/μL within 3 months of current
 TTP presentation

 15. Hypersensitivities or allergies to murine and/or humanized antibodies

 16. Current participation in trials of investigational therapies or devices, other than
 central catheters