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

• Sponsor: HealthCore-NERI (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00799773
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), Genentech, Inc. (Industry)
• Enrollment: 3
• Locations: 23
• Arms: 2
• Duration (Months): 10.1
• Patients Per Site: 0.1
• Patients Per Site Per Month: 0

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Thrombotic Thrombocytopenic Purpura	Drug: Rituximab; Procedure: Plasma exchange; Drug: Corticosteroids	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: STAR - Study of TTP and Rituximab, A Randomized Clinical Trial
• Study Start Date: Apr 1, 2009
• Actual Primary Completion Date: Feb 1, 2010
• Actual Study Completion Date: Feb 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

1. Use of Non-study Treatment [Measured at Month 36]

2. 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]

3. Relationship Between Clinical and Laboratory Data and Response to Treatment [Measured at Days 52 and 82]

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

5. All Cause Mortality [Measured at Month 36]

6. Treatment-related Complications [Measured at Day 52]

7. 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 [Measured at Month 36]

8. Rituximab Response in Participants With Varying Levels of ADAMTS-13 Activity and Antibodies Against ADAMTS-13 [Measured at Month 36]

9. Effect of Plasma Exchange on Rituximab Levels [Measured at Month 6]

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

11. 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 [Measured at Month 12]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama, Birmingham	Birmingham	Alabama	United States	35249
2	Emory University	Atlanta	Georgia	United States	30322
3	University of Iowa	Iowa City	Iowa	United States	52242
4	Tulane University Health Sciences Center	New Orleans	Louisiana	United States	70112
5	University of Maryland Medical Center	Baltimore	Maryland	United States	21201
6	Johns Hopkins Hospital	Baltimore	Maryland	United States	21205
7	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
8	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115
9	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
10	Children's Hospital Boston	Boston	Massachusetts	United States	02115
11	New York-Presbyterian Hospital/Weill Cornell Medical Center	New York	New York	United States	10021
12	University of North Carolina Hospitals	Chapel Hill	North Carolina	United States	27514
13	Duke University Medical Center	Durham	North Carolina	United States	27710
14	University Hospital Cleveland	Cleveland	Ohio	United States	44106
15	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
16	Integris Baptist Medical Center	Oklahoma City	Oklahoma	United States	73112
17	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
18	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
19	University of Pittsburgh Presbyterian and Shadyside Hospital	Pittsburgh	Pennsylvania	United States	15213
20	Puget Sound Blood Center	Seattle	Washington	United States	98104
21	Gunderson Clinic, LTD	LaCrosse	Wisconsin	United States	54601
22	University of Wisconsin at Madison	Madison	Wisconsin	United States	53792
23	Froedtert Memorial Lutheran Hospital	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• HealthCore-NERI
• National Heart, Lung, and Blood Institute (NHLBI)
• Genentech, Inc.

Investigators

• Principal Investigator: 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
• Study Chair: Joseph Kiss, MD, University of Pittsburgh

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: HealthCore-NERI
• ClinicalTrials.gov Identifier: NCT00799773
• Other Study ID Numbers: 558; U01HL072268; HL072268; HL072033; HL072291; HL072196; HL072248; HL072191; HL072305; HL072028; HL072072; HL072355; HL072283; HL072346; HL072331; HL072290
• First Posted: Dec 1, 2008
• Last Update Posted: Jul 22, 2013
• Last Verified: Jul 1, 2013

• Keywords provided by HealthCore-NERI: TTP; Rituximab; Plasma Exchange
• Additional relevant MeSH terms: Purpura; Purpura, Thrombocytopenic; Purpura, Thrombotic Thrombocytopenic; Rituximab

Study Results

Participant Flow

Arm/Group Title	Rituximab	Standard of Care
Arm/Group Description	Participants will receive rituximab in addition to plasma exchange and corticosteroids.	Participants will receive plasma exchange and corticosteroids.
Period Title: Overall Study
STARTED	2	1
COMPLETED	2	1
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Rituximab	Standard of Care	Total
Arm/Group Description	Participants will receive rituximab in addition to plasma exchange and corticosteroids.	Participants will receive plasma exchange and corticosteroids.	Total of all reporting groups
Overall Participants	2	1	3
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 100%	1 100%	3 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.5 (26.2)	24	37 (22)
Sex: Female, Male (Count of Participants)
Female	2 100%	1 100%	3 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	2 100%	1 100%	3 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The STAR informed consent form told subjects their data would be combined with other subjects' data in study reports. Because one treatment arm included only one subject, this subject's data cannot be combined with other subjects' data. Therefore, to protect subject confidentiality, results are not being released for this study.

Arm/Group Title	Rituximab	Standard of Care
Arm/Group Description	Participants will receive rituximab in addition to plasma exchange and corticosteroids.	Participants will receive plasma exchange and corticosteroids.
Measure Participants	0	0

2. Secondary Outcome

Title	Use of Non-study Treatment
Time Frame	Measured at Month 36

Outcome Measure Data

Analysis Population Description

The STAR informed consent form told subjects their data would be combined with other subjects' data in study reports. Because one treatment arm included only one subject, this subject's data cannot be combined with other subjects' data. Therefore, to protect subject confidentiality, results are not being released for this study.

Arm/Group Title	Rituximab	Standard of Care
Arm/Group Description	Participants will receive rituximab in addition to plasma exchange and corticosteroids.	Participants will receive plasma exchange and corticosteroids.
Measure Participants	0	0

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The STAR informed consent form told subjects their data would be combined with other subjects' data in study reports. Because one treatment arm included only one subject, this subject's data cannot be combined with other subjects' data. Therefore, to protect subject confidentiality, results are not being released for this study.

Arm/Group Title	Rituximab	Standard of Care
Arm/Group Description	Participants will receive rituximab in addition to plasma exchange and corticosteroids.	Participants will receive plasma exchange and corticosteroids.
Measure Participants	0	0

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The STAR informed consent form told subjects their data would be combined with other subjects' data in study reports. Because one treatment arm included only one subject, this subject's data cannot be combined with other subjects' data. Therefore, to protect subject confidentiality, results are not being released for this study.

Arm/Group Title	Rituximab	Standard of Care
Arm/Group Description	Participants will receive rituximab in addition to plasma exchange and corticosteroids.	Participants will receive plasma exchange and corticosteroids.
Measure Participants	0	0

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The STAR informed consent form told subjects their data would be combined with other subjects' data in study reports. Because one treatment arm included only one subject, this subject's data cannot be combined with other subjects' data. Therefore, to protect subject confidentiality, results are not being released for this study.

Arm/Group Title	Rituximab	Standard of Care
Arm/Group Description	Participants will receive rituximab in addition to plasma exchange and corticosteroids.	Participants will receive plasma exchange and corticosteroids.
Measure Participants	0	0

6. Secondary Outcome

Title	All Cause Mortality
Time Frame	Measured at Month 36

Outcome Measure Data

Analysis Population Description

The STAR informed consent form told subjects their data would be combined with other subjects' data in study reports. Because one treatment arm included only one subject, this subject's data cannot be combined with other subjects' data. Therefore, to protect subject confidentiality, results are not being released for this study.

Arm/Group Title	Rituximab	Standard of Care
Arm/Group Description	Participants will receive rituximab in addition to plasma exchange and corticosteroids.	Participants will receive plasma exchange and corticosteroids.
Measure Participants	0	0

7. Secondary Outcome

Title	Treatment-related Complications
Time Frame	Measured at Day 52

Outcome Measure Data

Analysis Population Description

The STAR informed consent form told subjects their data would be combined with other subjects' data in study reports. Because one treatment arm included only one subject, this subject's data cannot be combined with other subjects' data. Therefore, to protect subject confidentiality, results are not being released for this study.

Arm/Group Title	Rituximab	Standard of Care
Arm/Group Description	Participants will receive rituximab in addition to plasma exchange and corticosteroids.	Participants will receive plasma exchange and corticosteroids.
Measure Participants	0	0

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The STAR informed consent form told subjects their data would be combined with other subjects' data in study reports. Because one treatment arm included only one subject, this subject's data cannot be combined with other subjects' data. Therefore, to protect subject confidentiality, results are not being released for this study.

Arm/Group Title	Rituximab	Standard of Care
Arm/Group Description	Participants will receive rituximab in addition to plasma exchange and corticosteroids.	Participants will receive plasma exchange and corticosteroids.
Measure Participants	0	0

9. Secondary Outcome

Title	Rituximab Response in Participants With Varying Levels of ADAMTS-13 Activity and Antibodies Against ADAMTS-13
Time Frame	Measured at Month 36

Outcome Measure Data

Analysis Population Description

The STAR informed consent form told subjects their data would be combined with other subjects' data in study reports. Because one treatment arm included only one subject, this subject's data cannot be combined with other subjects' data. Therefore, to protect subject confidentiality, results are not being released for this study.

Arm/Group Title	Rituximab	Standard of Care
Arm/Group Description	Participants will receive rituximab in addition to plasma exchange and corticosteroids.	Participants will receive plasma exchange and corticosteroids.
Measure Participants	0	0

10. Secondary Outcome

Title	Effect of Plasma Exchange on Rituximab Levels
Time Frame	Measured at Month 6

Outcome Measure Data

Analysis Population Description

The STAR informed consent form told subjects their data would be combined with other subjects' data in study reports. Because one treatment arm included only one subject, this subject's data cannot be combined with other subjects' data. Therefore, to protect subject confidentiality, results are not being released for this study.

Arm/Group Title	Rituximab	Standard of Care
Arm/Group Description	Participants will receive rituximab in addition to plasma exchange and corticosteroids.	Participants will receive plasma exchange and corticosteroids.
Measure Participants	0	0

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The STAR informed consent form told subjects their data would be combined with other subjects' data in study reports. Because one treatment arm included only one subject, this subject's data cannot be combined with other subjects' data. Therefore, to protect subject confidentiality, results are not being released for this study.

Arm/Group Title	Rituximab	Standard of Care
Arm/Group Description	Participants will receive rituximab in addition to plasma exchange and corticosteroids.	Participants will receive plasma exchange and corticosteroids.
Measure Participants	0	0

12. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The STAR informed consent form told subjects their data would be combined with other subjects' data in study reports. Because one treatment arm included only one subject, this subject's data cannot be combined with other subjects' data. Therefore, to protect subject confidentiality, results are not being released for this study.

Arm/Group Title	Rituximab	Standard of Care
Arm/Group Description	Participants will receive rituximab in addition to plasma exchange and corticosteroids.	Participants will receive plasma exchange and corticosteroids.
Measure Participants	0	0

Adverse Events

Adverse Event Reporting Description	The STAR informed consent form told subjects their data would be combined with other subjects' data in study reports. Because one treatment arm included only one subject, to protect subject confidentiality adverse events, though collected, are not being reported for this study.
Arm/Group Title	Rituximab		Standard of Care
Arm/Group Description	Participants will receive rituximab in addition to plasma exchange and corticosteroids.		Participants will receive plasma exchange and corticosteroids.
All Cause Mortality
	Rituximab		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Rituximab		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Rituximab		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

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

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.