Back to resultsLow Dose Rituximab in Thrombotic Thrombocytopenic Purpura
Primary Purpose
Thrombotic Thrombocytopenic Purpura
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
rituximab
Sponsored by
About this trial
This is an interventional treatment trial for Thrombotic Thrombocytopenic Purpura focused on measuring ADAMTS13, Rituximab, Thrombotic thrombocytopenic purpura, TTP, Plasma exchange
Eligibility Criteria
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
Sites / Locations
- Emory University
- Beth Israel Deaconess Medical Center
- Washington University
- Duke University Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
low dose rituximab
Arm Description
this is a single-arm trial
Outcomes
Primary Outcome Measures
Incidence of the Composite Primary Outcome of Exacerbation or Refractory TTP
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
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
Number of Days to Durable Treatment Response
Median time to treatment response
Incidence of Relapse
Relapse is recurring TTP >30 days after Treatment Response
Months to Relapse
Mean months to relapse
Incidence of Death
Incidence of death will be assessed at 4 weeks, 1 year and 2 years
Treatment-related Adverse Events
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.
Full Information
NCT ID
NCT01554514
First Posted
March 8, 2012
Last Updated
August 13, 2021
Sponsor
Washington University School of Medicine
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT01554514
Brief Title
Low Dose Rituximab in Thrombotic Thrombocytopenic Purpura
Official Title
Adjuvant Low Dose Rituximab for Acquired TTP With Severe ADAMTS13 Deficiency
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Completed
Study Start Date
August 2012 (undefined)
Primary Completion Date
February 14, 2020 (Actual)
Study Completion Date
February 14, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thrombotic Thrombocytopenic Purpura
Keywords
ADAMTS13, Rituximab, Thrombotic thrombocytopenic purpura, TTP, Plasma exchange
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
low dose rituximab
Arm Type
Experimental
Arm Description
this is a single-arm trial
Intervention Type
Biological
Intervention Name(s)
rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
rituximab intravenously 100 mg every week for four doses
Primary Outcome Measure Information:
Title
Incidence of the Composite Primary Outcome of Exacerbation or Refractory TTP
Description
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.
Time Frame
60 days
Secondary Outcome Measure Information:
Title
Incidence of Durable Treatment Response
Description
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
Time Frame
60 days
Title
Number of Days to Durable Treatment Response
Description
Median time to treatment response
Time Frame
60 days
Title
Incidence of Relapse
Description
Relapse is recurring TTP >30 days after Treatment Response
Time Frame
Between 30 days and 2 years
Title
Months to Relapse
Description
Mean months to relapse
Time Frame
2 years
Title
Incidence of Death
Description
Incidence of death will be assessed at 4 weeks, 1 year and 2 years
Time Frame
2 years
Title
Treatment-related Adverse Events
Description
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.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elaine M Majerus, MD, PhD
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
21926591
Citation
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.
Results Reference
background
PubMed Identifier
20058208
Citation
Kiss JE. Thrombotic thrombocytopenic purpura: recognition and management. Int J Hematol. 2010 Jan;91(1):36-45. doi: 10.1007/s12185-009-0478-z.
Results Reference
result
PubMed Identifier
23279219
Citation
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.
Results Reference
result
PubMed Identifier
15389904
Citation
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.
Results Reference
result
PubMed Identifier
12353309
Citation
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.
Results Reference
result
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Low Dose Rituximab in Thrombotic Thrombocytopenic Purpura
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