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Low Dose Rituximab in Thrombotic Thrombocytopenic Purpura

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ClinicalTrials.gov Identifier: NCT01554514
Recruitment Status : Completed
First Posted : March 15, 2012
Results First Posted : August 13, 2021
Last Update Posted : August 17, 2021
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Thrombotic Thrombocytopenic Purpura Biological: rituximab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Adjuvant Low Dose Rituximab for Acquired TTP With Severe ADAMTS13 Deficiency
Study Start Date : August 2012
Actual Primary Completion Date : February 14, 2020
Actual Study Completion Date : February 14, 2020

Arm Intervention/treatment
Experimental: low dose rituximab
this is a single-arm trial
Biological: rituximab
rituximab intravenously 100 mg every week for four doses
Other Name: Rituxan

Primary Outcome Measures :
  1. Incidence of the Composite Primary Outcome of Exacerbation or Refractory TTP [ Time Frame: 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 :
  1. Incidence of Durable Treatment Response [ Time Frame: 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

  2. Number of Days to Durable Treatment Response [ Time Frame: 60 days ]
    Median time to treatment response

  3. Incidence of Relapse [ Time Frame: Between 30 days and 2 years ]
    Relapse is recurring TTP >30 days after Treatment Response

  4. Months to Relapse [ Time Frame: 2 years ]
    Mean months to relapse

  5. Incidence of Death [ Time Frame: 2 years ]
    Incidence of death will be assessed at 4 weeks, 1 year and 2 years

  6. Treatment-related Adverse Events [ Time Frame: 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.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01554514

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United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Missouri
Washington University
Saint Louis, Missouri, United States, 63110
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Washington University School of Medicine
National Heart, Lung, and Blood Institute (NHLBI)
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Principal Investigator: Elaine M Majerus, MD, PhD Washington University School of Medicine
  Study Documents (Full-Text)

Documents provided by Washington University School of Medicine:
Publications of Results:
Other Publications:
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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01554514    
Other Study ID Numbers: 201108256-LDrituximab
1U54HL112303-01 ( U.S. NIH Grant/Contract )
First Posted: March 15, 2012    Key Record Dates
Results First Posted: August 13, 2021
Last Update Posted: August 17, 2021
Last Verified: August 2021
Keywords provided by Washington University School of Medicine:
Thrombotic thrombocytopenic purpura
Plasma exchange
Additional relevant MeSH terms:
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Purpura, Thrombocytopenic
Purpura, Thrombotic Thrombocytopenic
Blood Coagulation Disorders
Hematologic Diseases
Pathologic Processes
Skin Manifestations
Thrombotic Microangiopathies
Blood Platelet Disorders
Immune System Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents