Low Dose Rituximab in Thrombotic Thrombocytopenic Purpura
Condition: Thrombotic Thrombocytopenic Purpura
MeSH terms: Purpura; Purpura, Thrombocytopenic; Purpura, Thrombotic Thrombocytopenic
Intervention: rituximab
Intervention description: rituximab intravenously 100 mg every week for four doses
Intervention MeSH terms: Rituximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ADAMTS13; Rituximab; Thrombotic thrombocytopenic purpura; TTP; Plasma exchange

Summary:

      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.
    

Eligibility criteria:

        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