- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01554514
Low Dose Rituximab in Thrombotic Thrombocytopenic Purpura
August 13, 2021 updated by: Washington University School of Medicine
Adjuvant Low Dose Rituximab for Acquired TTP With Severe ADAMTS13 Deficiency
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
19
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Georgia
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Atlanta, Georgia, United States, 30322
- Emory University
-
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Beth Israel Deaconess Medical Center
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Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University
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North Carolina
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Durham, North Carolina, United States, 27710
- Duke University Medical Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Age 18 or greater
Diagnosis of suspected thrombotic thrombocytopenic purpura (TTP)
- Platelet count of < 80,000 for newly diagnosed patients and < 120,000 for relapsed patients
- Microangiopathic hemolytic anemia with RBC fragmentation
- LDH >1 x ULN
- Subjects who will receive treatment for TTP with plasma exchange
- Subjects who have not started the 5th plasma exchange
- Plasma ADAMTS13 activity <10%
Exclusion Criteria:
- Treatment for TTP within the past 2 months
- 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
- Currently under treatment for 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 (sirolimus, tacrolimus, cyclosporin A) within 6 months prior to diagnosis of TTP
Disseminated intravascular coagulation as defined by:
a. INR >2.0 (unrelated to anticoagulation, unresponsive to Vitamin K) or b. Fibrinogen <100 mg/dl
- Pregnancy
- Known congenital TTP.
- Rituximab within the previous year.
- HIV history or positive serology
- History of hepatitis B or positive serology for HBsAg or Anti-HBc
- Persistent or unexplained platelet count below 150,000/μL within 3 months of current TTP presentation
- Hypersensitivities or allergies to murine and/or humanized antibodies
- Current participation in trials of investigational therapies or devices, other than central catheters
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: low dose rituximab
this is a single-arm trial
|
rituximab intravenously 100 mg every week for four doses
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
60 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
60 days
|
Number of Days to Durable Treatment Response
Time Frame: 60 days
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Median time to treatment response
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60 days
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Incidence of Relapse
Time Frame: Between 30 days and 2 years
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Relapse is recurring TTP >30 days after Treatment Response
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Between 30 days and 2 years
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Months to Relapse
Time Frame: 2 years
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Mean months to relapse
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2 years
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Incidence of Death
Time Frame: 2 years
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Incidence of death will be assessed at 4 weeks, 1 year and 2 years
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2 years
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Treatment-related Adverse Events
Time Frame: 2 years
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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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2 years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Elaine M Majerus, MD, PhD, Washington University School of Medicine
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Froissart A, Buffet M, Veyradier A, Poullin P, Provot F, Malot S, Schwarzinger M, Galicier L, Vanhille P, Vernant JP, Bordessoule D, Guidet B, Azoulay E, Mariotte E, Rondeau E, Mira JP, Wynckel A, Clabault K, Choukroun G, Presne C, Pourrat J, Hamidou M, Coppo P; French Thrombotic Microangiopathies Reference Center. Efficacy and safety of first-line rituximab in severe, acquired thrombotic thrombocytopenic purpura with a suboptimal response to plasma exchange. Experience of the French Thrombotic Microangiopathies Reference Center. Crit Care Med. 2012 Jan;40(1):104-11. doi: 10.1097/CCM.0b013e31822e9d66.
- Kiss JE. Thrombotic thrombocytopenic purpura: recognition and management. Int J Hematol. 2010 Jan;91(1):36-45. doi: 10.1007/s12185-009-0478-z.
- Westwood JP, Webster H, McGuckin S, McDonald V, Machin SJ, Scully M. Rituximab for thrombotic thrombocytopenic purpura: benefit of early administration during acute episodes and use of prophylaxis to prevent relapse. J Thromb Haemost. 2013 Mar;11(3):481-90. doi: 10.1111/jth.12114.
- Ahmad A, Aggarwal A, Sharma D, Dave HP, Kinsella V, Rick ME, Schechter GP. Rituximab for treatment of refractory/relapsing thrombotic thrombocytopenic purpura (TTP). Am J Hematol. 2004 Oct;77(2):171-6. doi: 10.1002/ajh.20166.
- Chemnitz J, Draube A, Scheid C, Staib P, Schulz A, Diehl V, Sohngen D. Successful treatment of severe thrombotic thrombocytopenic purpura with the monoclonal antibody rituximab. Am J Hematol. 2002 Oct;71(2):105-8. doi: 10.1002/ajh.10204.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
August 1, 2012
Primary Completion (Actual)
February 14, 2020
Study Completion (Actual)
February 14, 2020
Study Registration Dates
First Submitted
March 8, 2012
First Submitted That Met QC Criteria
March 13, 2012
First Posted (Estimate)
March 15, 2012
Study Record Updates
Last Update Posted (Actual)
August 17, 2021
Last Update Submitted That Met QC Criteria
August 13, 2021
Last Verified
August 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Hematologic Diseases
- Hemorrhage
- Blood Coagulation Disorders
- Skin Manifestations
- Thrombocytopenia
- Blood Platelet Disorders
- Thrombophilia
- Thrombotic Microangiopathies
- Purpura
- Purpura, Thrombocytopenic
- Purpura, Thrombotic Thrombocytopenic
- Physiological Effects of Drugs
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Rituximab
Other Study ID Numbers
- 201108256-LDrituximab
- 1U54HL112303-01 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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