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

NCT00799773 | Terminated Phase 3 Results DMC

• 16 other identifiers: 558U01HL072268HL072268HL072033HL072291HL072196HL072248HL072191HL072305HL072028HL072072HL072355HL072283HL072346HL072331HL072290
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 23

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.

Conditions

Thrombotic Thrombocytopenic Purpura

Keywords

TTP; Rituximab; Plasma Exchange

Outcome Measures

Primary Outcomes (1)

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

  Measured at Day 52

Secondary Outcomes (11)

• Use of Non-study Treatment

  Measured at Month 36

• Whether Participants Receiving Rituximab Achieve Early or Late Treatment Response Faster and Require Fewer Plasma Exchanges Than Participants Not Receiving Rituximab

  Measured at Days 52 and 82

• Relationship Between Clinical and Laboratory Data and Response to Treatment

  Measured at Days 52 and 82

• Incidence of Relapse Among Participants in the Two Study Groups Who Achieve Early Treatment Response

  Measured at Month 36

• All Cause Mortality

  Measured at Month 36

Study Arms (2)

1

EXPERIMENTAL

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

Drug: Rituximab; Procedure: Plasma exchange; Drug: Corticosteroids

2

ACTIVE COMPARATOR

Participants will receive plasma exchange and corticosteroids.

Procedure: Plasma exchange; Drug: Corticosteroids

Interventions

Rituximab DRUG

Dose of 375 mg/m2, given intravenously, repeated at 1-week intervals for a total of four doses

Also known as: Rituxan

1

Plasma exchange PROCEDURE

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.

1; 2

Corticosteroids DRUG

1 mg/kg of prednisone (or equivalent) each day until plasma exchange is stopped

1; 2

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Carelon Research: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Genentech, Inc.: collaborator

Study Sites (23)

University of Alabama, Birmingham

Birmingham, Alabama, 35249, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Tulane University Health Sciences Center

New Orleans, Louisiana, 70112, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21205, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

New York-Presbyterian Hospital/Weill Cornell Medical Center

New York, New York, 10021, United States

Location

University of North Carolina Hospitals

Chapel Hill, North Carolina, 27514, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University Hospital Cleveland

Cleveland, Ohio, 44106, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Integris Baptist Medical Center

Oklahoma City, Oklahoma, 73112, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Pittsburgh Presbyterian and Shadyside Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

Puget Sound Blood Center

Seattle, Washington, 98104, United States

Location

Gunderson Clinic, LTD

La Crosse, Wisconsin, 54601, United States

Location

University of Wisconsin at Madison

Madison, Wisconsin, 53792, United States

Location

Froedtert Memorial Lutheran Hospital

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Purpura, Thrombotic Thrombocytopenic

Interventions

Rituximab; Plasma Exchange; Adrenal Cortex Hormones

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Thrombophilia; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Blood Transfusion; Biological Therapy; Therapeutics; Plasmapheresis; Blood Component Removal; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

One treatment arm had only one subject, so to protect patient confidentiality, results are not being entered.

Results Point of Contact

• Title: Susan F. Assmann, PhD
• Organization: New England Research Institutes, Inc.

sassmann@neriscience.com

617-923-7747

Study Officials

• Susan F. Assmann, PhD

  New England Research Institutes, Inc.

  PRINCIPAL INVESTIGATOR

• Jan McFarland, MD

  Froedtert Hospital

  PRINCIPAL INVESTIGATOR

• Eliot Williams, MD, PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

• Keith McCrae, MD

  University Hospitals Cleveland Medical Center

  PRINCIPAL INVESTIGATOR

• Ellis Neufeld, MD

  Boston Children's Hospital

  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

  PRINCIPAL INVESTIGATOR

• Joseph Kiss, MD

  University of Pittsburgh

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2008
• First Posted: December 1, 2008
• Study Start: April 1, 2009
• Primary Completion: February 1, 2010
• Study Completion: February 1, 2010
• Last Updated: July 22, 2013
• Results First Posted: July 22, 2013

Record last verified: 2013-07

Locations

US (23)