Low Dose Rituximab in Thrombotic Thrombocytopenic Purpura

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2014 by Washington University School of Medicine
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
J. Evan Sadler, M.D., Ph.D., Washington University
ClinicalTrials.gov Identifier:
First received: March 8, 2012
Last updated: October 1, 2015
Last verified: December 2014
Thrombotic thrombocytopenic purpura (TTP) is a disease characterized by small blood clots throughout the body that can damage major organs and cause death. TTP is treated with plasma exchange (also called "plasmapheresis"). Patients who do not respond initially to plasma exchange often are helped by later treatment with rituximab. The purpose of this study is to see whether combining low doses of rituximab with plasma exchange will help patients get better sooner and reduce the chance of getting TTP again.

Condition Intervention Phase
Thrombotic Thrombocytopenic Purpura
Biological: rituximab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Adjuvant Low Dose Rituximab for Acquired TTP With Severe ADAMTS13 Deficiency

Resource links provided by NLM:

Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Incidence of the composite primary outcome of exacerbation or refractory TTP [ Time Frame: 60 days ] [ Designated as safety issue: No ]
    Exacerbation is recurring TTP ≤30 days after a Treatment Response (normal platelet count for 2 days) and discontinuation of plasma exchange. Refractory TTP is failure to achieve a Treatment Response by day 28, or failure to achieve a Durable Treatment Response (lasting at least 30 days) by day 60.

Secondary Outcome Measures:
  • Incidence of Durable Treatment Response [ Time Frame: 60 days ] [ Designated as safety issue: No ]
    Treatment Response is 2 consecutive days with platelet count ≥150, 000/µL Durable Treatment Response is a Treatment Response that persists for ≥30 days after discontinuation of plasma exchange

  • Number of days to Durable Treatment Response [ Time Frame: 60 days ] [ Designated as safety issue: No ]
  • Incidence of Relapse [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Relapse is recurring TTP >30 days after Treatment Response

  • Number of days to Relapse [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Incidence of death [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Incidence of death will be assessed at 4 weeks, 1 year and 2 years

  • Treatment-related adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Incidence, type and severity of treatment-related adverse events will be assessed

Estimated Enrollment: 20
Study Start Date: August 2012
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: low dose rituximab Biological: rituximab
rituximab intravenously 100 mg every week for four doses
Other Name: Rituxan

Detailed Description:
This is a pilot safety/efficacy study of adjuvant low dose rituximab (100 mg/week x 4 doses) plus standard plasma exchange and corticosteroids for the treatment of thrombotic thrombocytopenic purpura (TTP) with severe ADAMTS13 deficiency. Results for study subjects will be compared to historical controls treated initially with plasma exchange and corticosteroids. This study proposes to test the hypothesis that adjuvant low dose rituximab may decrease the incidence of a composite primary endpoint (exacerbations or refractory disease) in acquired TTP with severe ADAMTS13 deficiency. A novel ADAMTS13 assay will be used to identify patients with TTP and severe ADAMTS13 deficiency for enrollment, and to assess the utility of ADAMST13 as a biomarker for response to therapy and prognosis.

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Age 18 or greater
  2. Diagnosis of suspected thrombotic thrombocytopenic purpura (TTP)

    1. Platelet count of < 80,000 for newly diagnosed patients and < 120,000 for relapsed patients
    2. Microangiopathic hemolytic anemia with RBC fragmentation
    3. LDH >2 x ULN for newly diagnosed patients and >1 x ULN for relapsed patients
  3. Subjects who will receive treatment for TTP with plasma exchange
  4. Subjects who have not started the 5th plasma exchange
  5. Plasma ADAMTS13 activity <10%

Exclusion Criteria:

  1. Treatment for TTP within the past 2 months
  2. Severe active infection indicated by sepsis (requirement for pressors with or without positive blood cultures) or clinical evidence of enteric infection with E. coli O157:H7 or related organism
  3. Currently under treatment for cancer (subjects with localized skin carcinoma will be accepted)
  4. Microangiopathic hemolytic anemia due to a mechanical heart valve
  5. Severe hypertension, as defined by systolic BP >180 AND diastolic BP >120, or papilledema
  6. Organ or stem cell transplant
  7. Use of calcineurin inhibitors (sirolimus, tacrolimus, cyclosporin A) within 6 months prior to diagnosis of TTP
  8. Disseminated intravascular coagulation as defined by:

    a. INR >2.0 (unrelated to anticoagulation, unresponsive to Vitamin K) or b. Fibrinogen <100 mg/dl

  9. Pregnancy
  10. Known congenital TTP.
  11. Rituximab within the previous year.
  12. HIV history or positive serology
  13. History of hepatitis B or positive serology for HBsAg or Anti-HBc
  14. Persistent or unexplained platelet count below 150,000/μL within 3 months of current TTP presentation
  15. Hypersensitivities or allergies to murine and/or humanized antibodies
  16. Current participation in trials of investigational therapies or devices, other than central catheters
  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: NCT01554514

United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Shannon Gleason    404-778-4334    shannon.gleason@emory.edu   
Principal Investigator: Ana Antun, MD         
Sub-Investigator: Martha Arellano, MD         
Sub-Investigator: Manila Gaddh, MD         
Sub-Investigator: Leonard T Heffner, MD         
Sub-Investigator: Anand P Jillella, MD         
Sub-Investigator: H Jean Khoury, MD         
Sub-Investigator: Jacques Galipeau, MD         
Sub-Investigator: Amelia Langston, MD         
Sub-Investigator: Vamsi Kota, MD         
Sub-Investigator: Zaid Al-Kadhimi, MD         
United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Anita Rodrigues    617-667-1939    aerodrig@bidmc.harvard.edu   
Contact: Emma Logan    617-667-5984    eklogan@bidmc.harvard.edu   
Principal Investigator: Jeffrey Zwicker, MD         
Sub-Investigator: Kenneth Bauer, MD         
Sub-Investigator: Ayad Hamdan, MD         
Sub-Investigator: Erik Uhlmann, MD         
United States, Missouri
Washington University Recruiting
St. Louis, Missouri, United States, 63110
Contact: Vanetta Worthy    314-362-9998    VWORTHY@DOM.wustl.edu   
Contact: Patricia Nieters, RN, BSN    314-362-3371    nietersp@mir.wustl.edu   
Principal Investigator: J E Sadler, MD         
Sub-Investigator: Morey Blinder, MD         
Sub-Investigator: Elaine Majerus         
Sub-Investigator: Stephen Oh, MD         
Sub-Investigator: Kristin Sanfilippo, MD         
Sub-Investigator: Theodore Thomas, MD         
Sub-Investigator: George Broze, MD         
Sub-Investigator: Siddhartha Devarakonda, MD         
Sub-Investigator: Lingling Du, MD         
Sub-Investigator: Charles Eby, MD         
Sub-Investigator: Tanner Johanns, MD         
Sub-Investigator: Timothy Ley, MD         
Sub-Investigator: Chih Yi Liao, MD         
Sub-Investigator: Daniel Link, MD         
Sub-Investigator: Joshua Muia, PhD         
Sub-Investigator: Thomas Regenbogen, MD         
Sub-Investigator: Suresh Vedantham, MD         
Sub-Investigator: Pavan Bhamidipati, MD         
Sub-Investigator: Douglas Tollefsen, MD         
United States, North Carolina
Duke University Medical Center Not yet recruiting
Durham, North Carolina, United States, 27710
Contact: Betty H Thames, RN, BSN    919-681-9564    elizabeth.thames@duke.edu   
Principal Investigator: Ara Metjian, MD         
Sub-Investigator: Thomas L Ortel, MD         
Sub-Investigator: Nirmish Shah, MD         
Sub-Investigator: Gowthami Arepally, MD         
Sub-Investigator: Toyosi Onwuemene, MD         
Sponsors and Collaborators
J. Evan Sadler, M.D., Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: J E Sadler, MD, PhD Washington University School of Medicine
  More Information

Responsible Party: J. Evan Sadler, M.D., Ph.D., Professor of Medicine, Washington University
ClinicalTrials.gov Identifier: NCT01554514     History of Changes
Other Study ID Numbers: LDrituximab
Study First Received: March 8, 2012
Last Updated: October 1, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Washington University School of Medicine:
Thrombotic thrombocytopenic purpura
Plasma exchange

Additional relevant MeSH terms:
Purpura, Thrombocytopenic
Purpura, Thrombotic Thrombocytopenic
Blood Coagulation Disorders
Blood Platelet Disorders
Hematologic Diseases
Immune System Diseases
Pathologic Processes
Signs and Symptoms
Skin Manifestations
Thrombotic Microangiopathies
Antineoplastic Agents
Antirheumatic Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2015