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Low Dose Rituximab in Thrombotic Thrombocytopenic Purpura

This study is currently recruiting participants.
Verified August 2012 by Washington University School of Medicine
Sponsor:
Information provided by (Responsible Party):
J. Evan Sadler, M.D., Ph.D., Washington University
ClinicalTrials.gov Identifier:
NCT01554514
First received: March 8, 2012
Last updated: August 20, 2012
Last verified: August 2012
History of Changes
  Purpose

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 Intervention Phase
Thrombotic Thrombocytopenic Purpura
 Biological: rituximab
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Adjuvant Low Dose Rituximab for Acquired TTP With Severe ADAMTS13 Deficiency

Resource links provided by NLM:

Drug Information available for: Rituximab
U.S. FDA Resources

Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Incidence of the composite primary outcome of exacerbation or refractory TTP [ Time Frame: 60 days ] [ Designated as safety issue: No ]
    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:
  • Incidence of Durable Treatment Response [ Time Frame: 60 days ] [ Designated as safety issue: No ]
    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

  • Number of days to Durable Treatment Response [ Time Frame: 60 days ] [ Designated as safety issue: No ]
  • Incidence of Relapse [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Relapse is recurring TTP >30 days after Treatment Response

  • Number of days to Relapse [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Incidence of death [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Incidence of death will be assessed at 4 weeks, 1 year and 2 years

  • Treatment-related adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Incidence, type and severity of treatment-related adverse events will be assessed


Estimated Enrollment: 20
Study Start Date: August 2012
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: low dose rituximab Biological: rituximab
rituximab intravenously 100 mg every week for four doses
Other Name: Rituxan

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of suspected thrombotic thrombocytopenic purpura (TTP)
  • Will receive treatment with plasma exchange
  • Plasma ADAMTS13 activity <10%

Exclusion Criteria:

  • Treatment for TTP within the past 2 months
  • Severe active infection
  • Current diagnosis of cancer (subjects with localized skin carcinoma will be accepted)
  • Microangiopathic hemolytic anemia due to a mechanical heart valve
  • Severe hypertension, as defined by systolic BP >180 AND diastolic BP >120, or papilledema
  • Organ or stem cell transplant
  • Use of calcineurin inhibitors within 6 months prior to diagnosis of TTP
  • Disseminated intravascular coagulation
  • Pregnancy
  • Known congenital TTP.
  • Rituximab within the previous year.
  • HIV positive
  • History of hepatitis B or positive serology for HBsAg or Anti-HBc
  • History of hepatitis C
  • Persistent or unexplained platelet count below 150,000/μL within 3 months
  • Hypersensitivities or allergies to murine and/or humanized antibodies
  • Current participation in trials of investigational therapies or devices, other than central catheters
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01554514

Locations
United States, Missouri
Washington University Recruiting
St. Louis, Missouri, United States, 63110
Contact: J E Sadler, MD, PhD     314-362-8802     esadler@wustl.edu    
Sponsors and Collaborators
J. Evan Sadler, M.D., Ph.D.
Investigators
Principal Investigator: J E Sadler, MD, PhD Washington University School of Medicine
  More Information

No publications provided

Responsible Party: J. Evan Sadler, M.D., Ph.D., Professor of Medicine, Washington University
ClinicalTrials.gov Identifier: NCT01554514     History of Changes
Other Study ID Numbers: LDrituximab
Study First Received: March 8, 2012
Last Updated: August 20, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Washington University School of Medicine:
ADAMTS13
Rituximab
Thrombotic thrombocytopenic purpura
TTP
Plasma exchange

Additional relevant MeSH terms:
Purpura
Purpura, Thrombocytopenic
Purpura, Thrombotic Thrombocytopenic
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Thrombotic Microangiopathies
Thrombocytopenia
 Blood Platelet Disorders
Immune System Diseases
Thrombophilia
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on June 18, 2013