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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00799773
• Date of registration: 26/11/2008
• Prospective Registration: Yes
• Primary sponsor: New England Research Institutes
• Public title: Evaluating the Effectiveness of Adding Rituximab to Standard Treatment for Thrombotic Thrombocytopenic Purpura (TTP) STAR
• Scientific title: STAR - Study of TTP and Rituximab, A Randomized Clinical Trial
• Date of first enrolment: April 2009
• Target sample size: 3
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT00799773
• Study type: Interventional
• Phase: Phase 3

Countries of recruitment

United States

Contacts

• Name: Thomas Ortel, MD
• Affiliation: Duke University

• Name: Jan McFarland, MD
• Affiliation: Froedtert Memorial Lutheran Hospital

• Name: David Kuter, MD
• Affiliation: Massachusetts General Hospital

• Name: James Bussel, MD
• Affiliation: Weill Medical Colllege, Cornell University

• Name: Keith McCrae, MD
• Affiliation: University Hospitals Cleveland Medical Center

• Name: Darrell Triulzi, MD
• Affiliation: University of Pittsburgh Presbyterian and Shadyside/Children's Hospital Pittsburgh

• Name: Ellis Neufeld, MD
• Affiliation: Boston Children’s Hospital

• Name: Susan F. Assmann, PhD
• Affiliation: New England Research Institutes, Inc.

• Name: Mark Brecher, MD
• Affiliation: University of North Carolina, Chapel Hill

• Name: Joseph Kiss, MD
• Affiliation: University of Pittsburgh

• Name: Christopher Hillyer, MD
• Affiliation: Emory University

• Name: Cindy Leissinger, MD
• Affiliation: Tulane University

• Name: John Hess, MD
• Affiliation: University of Maryland

• Name: James George, MD
• Affiliation: University of Oklahoma

• Name: Eliot Williams, MD, PhD
• Affiliation: University of Wisconsin, Madison

• Name: Paul Ness, MD
• Affiliation: Johns Hopkins University

• Name: Barbara Konkle, MD
• Affiliation: University of Pennsylvania

• Name: Sherrill Slichter, MD
• Affiliation: University of Washington Medical Center/Fred Hutchinson Cancer Research Center (FHCRC)

• Name: Ronald Strauss, MD
• Affiliation: University of Iowa

Key inclusion & exclusion 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



Age minimum: 12 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Thrombotic Thrombocytopenic Purpura

Intervention(s)

Drug: Rituximab

Drug: Corticosteroids

Procedure: Plasma exchange

Primary Outcome(s)

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(s)

Treatment-related Complications [Time Frame: Measured at Day 52]

Use of Non-study Treatment [Time Frame: Measured at Month 36]

All Cause Mortality [Time Frame: Measured at Month 36]

Effect of Rituximab Levels on the Extent of B-cell Depletion (CD-19+ Cells) [Time Frame: Measured at Month 12]

Effect of Plasma Exchange on Rituximab Levels [Time Frame: Measured at Month 6]

Incidence of Relapse Among Participants in the Two Study Groups Who Achieve Early Treatment Response [Time Frame: Measured at Month 36]

Relationship Between Clinical and Laboratory Data and Response to Treatment [Time Frame: Measured at Days 52 and 82]

Rituximab Response in Participants With Varying Levels of ADAMTS-13 Activity and Antibodies Against ADAMTS-13 [Time Frame: 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 [Time Frame: Measured at Days 52 and 82]

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]

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]

Secondary ID(s)

HL072072

HL072248

HL072305

U01HL072268

HL072196

HL072291

HL072355

HL072028

HL072346

558

HL072191

HL072033

HL072283

HL072268

HL072290

HL072331

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Heart, Lung, and Blood Institute (NHLBI)

Genentech, Inc.

Results

• Results available: Yes
• Date Posted: 22/07/2013
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00799773