Low Dose Rituximab in Thrombotic Thrombocytopenic Purpura

The Washington University

Status and phase: Completed; Phase 2

Conditions: Thrombotic Thrombocytopenic Purpura

Treatments: Biological: rituximab

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01554514

201108256-LDrituximab

1U54HL112303-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 19 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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19 participants in 1 patient group

low dose rituximab

Experimental group

Description:

this is a single-arm trial

Treatment:

Biological: rituximab