Low Dose Rituximab in Thrombotic Thrombocytopenic Purpura

Phase 2

Completed

• Conditions: Thrombotic Thrombocytopenic Purpura
• Interventions: Biological: rituximab

• Registration Number: NCT01554514
• Lead Sponsor: Washington University School of Medicine

Brief 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.

Detailed 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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2012-03-08
• Study First Submitted QC: 2012-03-13
• Study First Posted: 2012-03-15
• Study Start: 2012-08
• Primary Completion: 2020-02-14
• Study Completion: 2020-02-14
• Results First Submitted: 2021-02-09
• Results First Submitted QC: 2021-07-21
• Status Verified: 2021-08
• Results First Posted: 2021-08-13
• Last Update Submitted: 2021-08-13
• Last Update Posted: 2021-08-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

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%

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
low dose rituximab	rituximab	this is a single-arm trial

Primary Outcome Measures

Name	Time	Method
Incidence of the Composite Primary Outcome of Exacerbation or Refractory TTP	60 days	Exacerbation is recurring TTP ≤30 days after a Treatment Response (normal platelet count for 2 days) and discontinuation of plasma exchange. Refractory TTP is failure to achieve a Treatment Response by day 28, or failure to achieve a Durable Treatment Response (lasting at least 30 days) by day 60.

Secondary Outcome Measures

Name	Time	Method
Number of Days to Durable Treatment Response	60 days	Median time to treatment response
Incidence of Relapse	Between 30 days and 2 years	Relapse is recurring TTP \>30 days after Treatment Response
Incidence of Durable Treatment Response	60 days	Treatment Response is 2 consecutive days with platelet count ≥150, 000/µL Durable Treatment Response is a Treatment Response that persists for ≥30 days after discontinuation of plasma exchange and includes those with exacerbations
Incidence of Death	2 years	Incidence of death will be assessed at 4 weeks, 1 year and 2 years
Treatment-related Adverse Events	2 years	Incidence, type and severity of treatment-related adverse events will be assessed. Patient reports, lab values, and physical exam were used to identify treatment-related adverse events.
Months to Relapse	2 years	Mean months to relapse

Trial Locations

Locations (4)

Emory University; 🇺🇸 Atlanta, Georgia, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Washington University; 🇺🇸 Saint Louis, Missouri, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States