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

This study has been terminated.
(Low enrollment rate)
Sponsor:
Collaborators:
Genentech
Information provided by (Responsible Party):
New England Research Institutes
ClinicalTrials.gov Identifier:
NCT00799773
First received: November 26, 2008
Last updated: July 18, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Thrombotic Thrombocytopenic Purpura
Drug: Rituximab
Procedure: Plasma exchange
Drug: Corticosteroids
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: STAR - Study of TTP and Rituximab, A Randomized Clinical Trial

Resource links provided by NLM:


Further study details as provided by New England Research Institutes:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Use of Non-study Treatment [ Time Frame: Measured at Month 36 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Relationship Between Clinical and Laboratory Data and Response to Treatment [ Time Frame: Measured at Days 52 and 82 ] [ Designated as safety issue: No ]
  • Incidence of Relapse Among Participants in the Two Study Groups Who Achieve Early Treatment Response [ Time Frame: Measured at Month 36 ] [ Designated as safety issue: No ]
  • All Cause Mortality [ Time Frame: Measured at Month 36 ] [ Designated as safety issue: No ]
  • Treatment-related Complications [ Time Frame: Measured at Day 52 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • Rituximab Response in Participants With Varying Levels of ADAMTS-13 Activity and Antibodies Against ADAMTS-13 [ Time Frame: Measured at Month 36 ] [ Designated as safety issue: No ]
  • Effect of Plasma Exchange on Rituximab Levels [ Time Frame: Measured at Month 6 ] [ Designated as safety issue: No ]
  • Effect of Rituximab Levels on the Extent of B-cell Depletion (CD-19+ Cells) [ Time Frame: Measured at Month 12 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 3
Study Start Date: April 2009
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Participants will receive rituximab in addition to plasma exchange and corticosteroids.
Drug: Rituximab
Dose of 375 mg/m2, given intravenously, repeated at 1-week intervals for a total of four doses
Other Name: Rituxan
Procedure: Plasma exchange
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.
Drug: Corticosteroids
1 mg/kg of prednisone (or equivalent) each day until plasma exchange is stopped
Active Comparator: 2
Participants will receive plasma exchange and corticosteroids.
Procedure: Plasma exchange
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.
Drug: Corticosteroids
1 mg/kg of prednisone (or equivalent) each day until plasma exchange is stopped

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.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00799773

Locations
United States, Alabama
University of Alabama, Birmingham
Birmingham, Alabama, United States, 35249
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Louisiana
Tulane University Health Sciences Center
New Orleans, Louisiana, United States, 70112
United States, Maryland
University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21205
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, New York
New York-Presbyterian Hospital/Weill Cornell Medical Center
New York, New York, United States, 10021
United States, North Carolina
University of North Carolina Hospitals
Chapel Hill, North Carolina, United States, 27514
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
University Hospital Cleveland
Cleveland, Ohio, United States, 44106
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
Integris Baptist Medical Center
Oklahoma City, Oklahoma, United States, 73112
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh Presbyterian and Shadyside Hospital
Pittsburgh, Pennsylvania, United States, 15213
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Washington
Puget Sound Blood Center
Seattle, Washington, United States, 98104
United States, Wisconsin
Gunderson Clinic, LTD
LaCrosse, Wisconsin, United States, 54601
University of Wisconsin at Madison
Madison, Wisconsin, United States, 53792
Froedtert Memorial Lutheran Hospital
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
New England Research Institutes
Genentech
Investigators
Principal Investigator: Susan F. Assmann, PhD New England Research Institutes, Inc.
Principal Investigator: Jan McFarland, MD Froedtert Memorial Lutheran Hospital
Principal Investigator: Eliot Williams, MD, PhD University of Wisconsin, Madison
Principal Investigator: Keith McCrae, MD University Hospital Case Medical Center
Principal Investigator: Ellis Neufeld, MD Children's Hospital Boston
Principal Investigator: James Bussel, MD Weill Medical Colllege, Cornell University
Principal Investigator: Thomas Ortel, MD Duke University
Principal Investigator: Christopher Hillyer, MD Emory University
Principal Investigator: Paul Ness, MD Johns Hopkins University
Principal Investigator: David Kuter, MD Massachusetts General Hospital
Principal Investigator: Sherrill Slichter, MD University of Washington Medical Center/Fred Hutchinson Cancer Research Center (FHCRC)
Principal Investigator: Cindy Leissinger, MD Tulane University
Principal Investigator: Ronald Strauss, MD University of Iowa
Principal Investigator: John Hess, MD University of Maryland
Principal Investigator: Mark Brecher, MD University of North Carolina, Chapel Hill
Principal Investigator: James George, MD University of Oklahoma
Principal Investigator: Barbara Konkle, MD University of Pennsylvania
Principal Investigator: Darrell Triulzi, MD University of Pittsburgh Presbyterian and Shadyside/Children's Hospital Pittsburgh
Study Chair: Joseph Kiss, MD University of Pittsburgh
  More Information

No publications provided

Responsible Party: New England Research Institutes
ClinicalTrials.gov Identifier: NCT00799773     History of Changes
Other Study ID Numbers: 558, U01HL072268, HL072268, HL072033, HL072291, HL072196, HL072248, HL072191, HL072305, HL072028, HL072072, HL072355, HL072283, HL072346, HL072331, HL072290
Study First Received: November 26, 2008
Results First Received: May 7, 2013
Last Updated: July 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by New England Research Institutes:
TTP
Rituximab
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
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 28, 2014