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Evaluating the Effectiveness of Adding Rituximab to Standard Treatment for Thrombotic Thrombocytopenic Purpura (TTP) (STAR)

Primary Purpose

Thrombotic Thrombocytopenic Purpura

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Rituximab
Plasma exchange
Corticosteroids
Sponsored by
Carelon Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Thrombotic Thrombocytopenic Purpura focused on measuring TTP, Rituximab, Plasma Exchange

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Differential or admission diagnosis of TTP-like syndrome, defined as the following:

    1. Platelet count of less than 80,000/µL for newly diagnosed patients and less than 120,000/µL for relapsed patients
    2. Microangiopathic hemolytic anemia (MHA) with red blood cell fragmentation
    3. Lactate dehydrogenase (LDH) level greater than two times the upper limit of normal for newly diagnosed patients and greater than the upper limit of normal for relapsed patients
  • Receiving or will receive treatment for TTP with plasma exchange
  • Has not started the sixth plasma exchange in the current TTP episode

Exclusion Criteria:

  • Treated for TTP in the 2 months before study entry
  • Previously enrolled in this study
  • Severe active infection indicated by sepsis (requirement for pressors with or without positive blood cultures) or clinical evidence of enteric infection with E. coli 0157 or related organism
  • Currently under treatment for cancer or has a current diagnosis of cancer (other than localized skin carcinoma)
  • Microangiopathic hemolytic anemia due to a mechanical heart valve
  • Severe high blood pressure, as defined by systolic blood pressure of greater than 180 and diastolic blood pressure of greater than 120, or papilledema
  • Has ever had an organ or stem cell transplant
  • Has received calcineurin inhibitors (e.g., sirolimus, tacrolimus, cyclosporin A) in the 6 months before TTP diagnosis
  • Diagnosis of disseminated intravascular coagulation (DIC), defined as the following:

    1. International normalized ratio (INR) level greater than 2.0 (unrelated to anticoagulation, unresponsive to vitamin K administration) OR
    2. Fibrinogen less than 100 mg/dL
  • Pregnant
  • Requires ventilator assistance or intravenous pressors for treatment of TTP. If no longer required prior to study entry, patient is eligible for the study.
  • Known congenital TTP or family history of TTP
  • Established diagnosis of lupus, and/or actively treated for lupus in the 60 days before study entry. In addition, people with two or more of the following systemic lupus erythematosus (SLE) clinical criteria in the 60 days before study entry will be excluded:

    1. Characteristic skin rash, either malar or photosensitive
    2. Symmetric polyarthritis
    3. Serositis, either pleurisy or pericarditis
  • Previously received rituximab
  • Has taken the following drugs known to be associated with TTP-like syndrome in the 3 months before study entry: clopidogrel (Plavix), ticlopidine (Ticlid), or quinine
  • Will receive more than 1.5 plasma volumes per day after study entry
  • HIV history or positive serology
  • History of hepatitis B or positive serology for HBsAg or Anti-hepatitis B core antigen (Anti-HBc)
  • History of hepatitis C
  • Known persistent or unexplained platelet count below 150,000/µL in the 3 months before current TTP episode
  • Known hypersensitivities or allergies to murine and/or humanized antibodies
  • Currently participating in trials of investigational therapies or devices (other than investigational central catheters)
  • Has ever had a diagnosis of ventricular tachycardia
  • Acute transmural heart attack during the current hospital admission

Sites / Locations

  • University of Alabama, Birmingham
  • Emory University
  • University of Iowa
  • Tulane University Health Sciences Center
  • University of Maryland Medical Center
  • Johns Hopkins Hospital
  • Massachusetts General Hospital
  • Beth Israel Deaconess Medical Center
  • Brigham and Women's Hospital
  • Children's Hospital Boston
  • New York-Presbyterian Hospital/Weill Cornell Medical Center
  • University of North Carolina Hospitals
  • Duke University Medical Center
  • University Hospital Cleveland
  • University of Oklahoma Health Sciences Center
  • Integris Baptist Medical Center
  • University of Pennsylvania
  • Children's Hospital of Pittsburgh
  • University of Pittsburgh Presbyterian and Shadyside Hospital
  • Puget Sound Blood Center
  • Gunderson Clinic, LTD
  • University of Wisconsin at Madison
  • Froedtert Memorial Lutheran Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

1

2

Arm Description

Participants will receive rituximab in addition to plasma exchange and corticosteroids.

Participants will receive plasma exchange and corticosteroids.

Outcomes

Primary Outcome Measures

Role of Rituximab in Increasing Early Treatment Response in Participants With TTP Who Are Also Treated With Plasma Exchange and Corticosteroids

Secondary Outcome Measures

Use of Non-study Treatment
Whether Participants Receiving Rituximab Achieve Early or Late Treatment Response Faster and Require Fewer Plasma Exchanges Than Participants Not Receiving Rituximab
Relationship Between Clinical and Laboratory Data and Response to Treatment
Incidence of Relapse Among Participants in the Two Study Groups Who Achieve Early Treatment Response
All Cause Mortality
Treatment-related Complications
Evaluating How Levels of ADAMTS-13 Enzyme and Autoantibody at Specific Time Points or Over the Course of the Study Correlate With Other Indicators of Disease Activity, Remission Rates, Rapidity of Achieving a Remission, and Recurrence Rate
Rituximab Response in Participants With Varying Levels of ADAMTS-13 Activity and Antibodies Against ADAMTS-13
Effect of Plasma Exchange on Rituximab Levels
Effect of Rituximab Levels on the Extent of B-cell Depletion (CD-19+ Cells)
B-cell Depletion in Relation to ADAMTS-13 Activity and to ADAMTS-13 Antibody Levels and Disease Activity in Participants Who Receive Rituximab Versus Those Who do Not

Full Information

First Posted
November 26, 2008
Last Updated
July 18, 2013
Sponsor
Carelon Research
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00799773
Brief Title
Evaluating the Effectiveness of Adding Rituximab to Standard Treatment for Thrombotic Thrombocytopenic Purpura (TTP)
Acronym
STAR
Official Title
STAR - Study of TTP and Rituximab, A Randomized Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
July 2013
Overall Recruitment Status
Terminated
Why Stopped
Low enrollment rate
Study Start Date
April 2009 (undefined)
Primary Completion Date
February 2010 (Actual)
Study Completion Date
February 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Carelon Research
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Genentech, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Thrombotic thrombocytopenic purpura (TTP) is a rare disorder that causes blood clots to form in blood vessels. The main treatment for TTP is plasma exchange, in which affected patients receive transfusions of plasma, the liquid part of blood, from healthy donors. This study will examine the effectiveness of an antibody, rituximab, in combination with plasma exchange, at improving the immune response in people with TTP and decreasing the recurrence of TTP.
Detailed Description
TTP is a disorder that causes blood clots to form in the small blood vessels throughout the body. If the clots in fact block the blood vessels, blood flow is restricted to various organs, including the brain, kidneys, and heart. This can lead to neurological problems, stroke, abnormal kidney function, and heart problems. Because a large number of platelets are used in the blood clotting process, people with TTP have a reduced number of platelets circulating in their blood. They also have fewer red blood cells circulating in their blood because the red blood cells break down prematurely as blood squeezes past a blood clot. The primary treatment for TTP is plasmapheresis, also called plasma exchange, which is a procedure that circulates a person's blood through a machine that first removes the damaged plasma and then adds healthy donor plasma into the blood. Next, patients receive a blood transfusion with the new blood. Corticosteroids, a type of medication that reduces the amount of antibodies a person's body makes, are also commonly used in conjunction with plasma exchange to treat TTP. Plasma exchange is usually effective, with platelet and red blood cell counts returning to normal after the procedure is complete. However, some people do experience a relapse of TTP and will require repeat plasma exchanges. Rituximab, an antibody currently used to treat lymphoma and rheumatoid arthritis, may improve immune system response and decrease the number of days needed to undergo the plasma exchange procedure. The purpose of this study is to evaluate the effectiveness of rituximab in combination with plasma exchange at improving an early treatment response in people with TTP and decreasing the likelihood of a relapse of TTP. This 3-year study will enroll people who have recently been diagnosed with TTP or recently experienced a relapse and have not yet had six plasma exchanges during the current episode of TTP. Participants will be randomly assigned to receive either plasma exchanges and corticosteroids or plasma exchanges, corticosteroids, and rituximab. Blood will be collected from participants at baseline and each day they undergo the plasma exchange procedure. All participants will receive a plasma exchange every day until their platelet counts are normal and signs of tissue damage have improved. Participants will receive corticosteroid medication every day until plasma exchange is stopped, at which time the dosage will be gradually tapered until 7 weeks after the last plasma exchange. Participants receiving rituximab will receive the first dose intravenously within 7 days of the first plasma exchange; they will continue to receive rituximab once a week for 4 weeks. After the plasma exchanges are completed, all participants will have routine follow-up care with their doctors to make sure there is no TTP relapse. In the 1 year after study entry, additional blood collections will occur at varying times. Study researchers will monitor participants' health in the 3 years after study entry by following up with their doctors or through periodic phone calls. A portion of blood will be collected and stored for future TTP research purposes; this is optional.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thrombotic Thrombocytopenic Purpura
Keywords
TTP, Rituximab, Plasma Exchange

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Participants will receive rituximab in addition to plasma exchange and corticosteroids.
Arm Title
2
Arm Type
Active Comparator
Arm Description
Participants will receive plasma exchange and corticosteroids.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
Dose of 375 mg/m2, given intravenously, repeated at 1-week intervals for a total of four doses
Intervention Type
Procedure
Intervention Name(s)
Plasma exchange
Intervention Description
Target volume of 1.25 plasma volume replacement; fresh frozen plasma (FFP) is the required replacement fluid; provided daily until platelet counts are normal and signs of tissue damage have improved.
Intervention Type
Drug
Intervention Name(s)
Corticosteroids
Intervention Description
1 mg/kg of prednisone (or equivalent) each day until plasma exchange is stopped
Primary Outcome Measure Information:
Title
Role of Rituximab in Increasing Early Treatment Response in Participants With TTP Who Are Also Treated With Plasma Exchange and Corticosteroids
Time Frame
Measured at Day 52
Secondary Outcome Measure Information:
Title
Use of Non-study Treatment
Time Frame
Measured at Month 36
Title
Whether Participants Receiving Rituximab Achieve Early or Late Treatment Response Faster and Require Fewer Plasma Exchanges Than Participants Not Receiving Rituximab
Time Frame
Measured at Days 52 and 82
Title
Relationship Between Clinical and Laboratory Data and Response to Treatment
Time Frame
Measured at Days 52 and 82
Title
Incidence of Relapse Among Participants in the Two Study Groups Who Achieve Early Treatment Response
Time Frame
Measured at Month 36
Title
All Cause Mortality
Time Frame
Measured at Month 36
Title
Treatment-related Complications
Time Frame
Measured at Day 52
Title
Evaluating How Levels of ADAMTS-13 Enzyme and Autoantibody at Specific Time Points or Over the Course of the Study Correlate With Other Indicators of Disease Activity, Remission Rates, Rapidity of Achieving a Remission, and Recurrence Rate
Time Frame
Measured at Month 36
Title
Rituximab Response in Participants With Varying Levels of ADAMTS-13 Activity and Antibodies Against ADAMTS-13
Time Frame
Measured at Month 36
Title
Effect of Plasma Exchange on Rituximab Levels
Time Frame
Measured at Month 6
Title
Effect of Rituximab Levels on the Extent of B-cell Depletion (CD-19+ Cells)
Time Frame
Measured at Month 12
Title
B-cell Depletion in Relation to ADAMTS-13 Activity and to ADAMTS-13 Antibody Levels and Disease Activity in Participants Who Receive Rituximab Versus Those Who do Not
Time Frame
Measured at Month 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Differential or admission diagnosis of TTP-like syndrome, defined as the following: Platelet count of less than 80,000/µL for newly diagnosed patients and less than 120,000/µL for relapsed patients Microangiopathic hemolytic anemia (MHA) with red blood cell fragmentation Lactate dehydrogenase (LDH) level greater than two times the upper limit of normal for newly diagnosed patients and greater than the upper limit of normal for relapsed patients Receiving or will receive treatment for TTP with plasma exchange Has not started the sixth plasma exchange in the current TTP episode Exclusion Criteria: Treated for TTP in the 2 months before study entry Previously enrolled in this study Severe active infection indicated by sepsis (requirement for pressors with or without positive blood cultures) or clinical evidence of enteric infection with E. coli 0157 or related organism Currently under treatment for cancer or has a current diagnosis of cancer (other than localized skin carcinoma) Microangiopathic hemolytic anemia due to a mechanical heart valve Severe high blood pressure, as defined by systolic blood pressure of greater than 180 and diastolic blood pressure of greater than 120, or papilledema Has ever had an organ or stem cell transplant Has received calcineurin inhibitors (e.g., sirolimus, tacrolimus, cyclosporin A) in the 6 months before TTP diagnosis Diagnosis of disseminated intravascular coagulation (DIC), defined as the following: International normalized ratio (INR) level greater than 2.0 (unrelated to anticoagulation, unresponsive to vitamin K administration) OR Fibrinogen less than 100 mg/dL Pregnant Requires ventilator assistance or intravenous pressors for treatment of TTP. If no longer required prior to study entry, patient is eligible for the study. Known congenital TTP or family history of TTP Established diagnosis of lupus, and/or actively treated for lupus in the 60 days before study entry. In addition, people with two or more of the following systemic lupus erythematosus (SLE) clinical criteria in the 60 days before study entry will be excluded: Characteristic skin rash, either malar or photosensitive Symmetric polyarthritis Serositis, either pleurisy or pericarditis Previously received rituximab Has taken the following drugs known to be associated with TTP-like syndrome in the 3 months before study entry: clopidogrel (Plavix), ticlopidine (Ticlid), or quinine Will receive more than 1.5 plasma volumes per day after study entry HIV history or positive serology History of hepatitis B or positive serology for HBsAg or Anti-hepatitis B core antigen (Anti-HBc) History of hepatitis C Known persistent or unexplained platelet count below 150,000/µL in the 3 months before current TTP episode Known hypersensitivities or allergies to murine and/or humanized antibodies Currently participating in trials of investigational therapies or devices (other than investigational central catheters) Has ever had a diagnosis of ventricular tachycardia Acute transmural heart attack during the current hospital admission
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susan F. Assmann, PhD
Organizational Affiliation
New England Research Institutes, Inc.
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jan McFarland, MD
Organizational Affiliation
Froedtert Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Eliot Williams, MD, PhD
Organizational Affiliation
University of Wisconsin, Madison
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Keith McCrae, MD
Organizational Affiliation
University Hospitals Cleveland Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ellis Neufeld, MD
Organizational Affiliation
Boston Children's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
James Bussel, MD
Organizational Affiliation
Weill Medical Colllege, Cornell University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Thomas Ortel, MD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Christopher Hillyer, MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Paul Ness, MD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David Kuter, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Sherrill Slichter, MD
Organizational Affiliation
University of Washington Medical Center/Fred Hutchinson Cancer Research Center (FHCRC)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Cindy Leissinger, MD
Organizational Affiliation
Tulane University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ronald Strauss, MD
Organizational Affiliation
University of Iowa
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
John Hess, MD
Organizational Affiliation
University of Maryland
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mark Brecher, MD
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
James George, MD
Organizational Affiliation
University of Oklahoma
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Barbara Konkle, MD
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Darrell Triulzi, MD
Organizational Affiliation
University of Pittsburgh Presbyterian and Shadyside/Children's Hospital Pittsburgh
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Joseph Kiss, MD
Organizational Affiliation
University of Pittsburgh
Official's Role
Study Chair
Facility Information:
Facility Name
University of Alabama, Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35249
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Tulane University Health Sciences Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
University of Maryland Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Children's Hospital Boston
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
New York-Presbyterian Hospital/Weill Cornell Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
University of North Carolina Hospitals
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
University Hospital Cleveland
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Integris Baptist Medical Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
University of Pittsburgh Presbyterian and Shadyside Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Puget Sound Blood Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Gunderson Clinic, LTD
City
LaCrosse
State/Province
Wisconsin
ZIP/Postal Code
54601
Country
United States
Facility Name
University of Wisconsin at Madison
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Froedtert Memorial Lutheran Hospital
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Evaluating the Effectiveness of Adding Rituximab to Standard Treatment for Thrombotic Thrombocytopenic Purpura (TTP)

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