Low Dose Rituximab in Thrombotic Thrombocytopenic Purpura

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