Low Dose Rituximab in Thrombotic Thrombocytopenic Purpura

NCT01554514 | Completed Phase 2 Results

• 2 other identifiers: 201108256-LDrituximab1U54HL112303-01
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Thrombotic Thrombocytopenic Purpura

Keywords

ADAMTS13; Rituximab; Thrombotic thrombocytopenic purpura; TTP; Plasma exchange

Outcome Measures

Primary Outcomes (1)

• Incidence of the Composite Primary Outcome of Exacerbation or Refractory TTP

  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.

  60 days

Secondary Outcomes (6)

• Incidence of Durable Treatment Response

  60 days

• Number of Days to Durable Treatment Response

  60 days

• Incidence of Relapse

  Between 30 days and 2 years

• Months to Relapse

  2 years

• Incidence of Death

  2 years

Study Arms (1)

low dose rituximab

EXPERIMENTAL

this is a single-arm trial

Biological: rituximab

Interventions

rituximab BIOLOGICAL

rituximab intravenously 100 mg every week for four doses

Also known as: Rituxan

low dose rituximab

Eligibility Criteria

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

You may qualify if:

• Age 18 or greater
• Diagnosis of suspected thrombotic thrombocytopenic purpura (TTP)
• Platelet count of \< 80,000 for newly diagnosed patients and \< 120,000 for relapsed patients
• Microangiopathic hemolytic anemia with RBC fragmentation
• LDH \>1 x ULN
• Subjects who will receive treatment for TTP with plasma exchange
• Subjects who have not started the 5th plasma exchange
• Plasma ADAMTS13 activity \<10%

You may not qualify if:

• Treatment for TTP within the past 2 months
• 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
• Currently under treatment for cancer (subjects with localized skin carcinoma will be accepted)
• Microangiopathic hemolytic anemia due to a mechanical heart valve
• Severe hypertension, as defined by systolic BP \>180 AND diastolic BP \>120, or papilledema
• Organ or stem cell transplant
• Use of calcineurin inhibitors (sirolimus, tacrolimus, cyclosporin A) within 6 months prior to diagnosis of TTP
• Disseminated intravascular coagulation as defined by:
• a. INR \>2.0 (unrelated to anticoagulation, unresponsive to Vitamin K) or b. Fibrinogen \<100 mg/dl
• Pregnancy
• Known congenital TTP.
• Rituximab within the previous year.
• HIV history or positive serology
• History of hepatitis B or positive serology for HBsAg or Anti-HBc
• Persistent or unexplained platelet count below 150,000/μL within 3 months of current TTP presentation

Sponsors & Collaborators

• Washington University School of Medicine: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (4)

Emory University

Atlanta, Georgia, 30322, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (5)

• Froissart A, Buffet M, Veyradier A, Poullin P, Provot F, Malot S, Schwarzinger M, Galicier L, Vanhille P, Vernant JP, Bordessoule D, Guidet B, Azoulay E, Mariotte E, Rondeau E, Mira JP, Wynckel A, Clabault K, Choukroun G, Presne C, Pourrat J, Hamidou M, Coppo P; French Thrombotic Microangiopathies Reference Center. Efficacy and safety of first-line rituximab in severe, acquired thrombotic thrombocytopenic purpura with a suboptimal response to plasma exchange. Experience of the French Thrombotic Microangiopathies Reference Center. Crit Care Med. 2012 Jan;40(1):104-11. doi: 10.1097/CCM.0b013e31822e9d66.

  PMID: 21926591 BACKGROUND

• Kiss JE. Thrombotic thrombocytopenic purpura: recognition and management. Int J Hematol. 2010 Jan;91(1):36-45. doi: 10.1007/s12185-009-0478-z.

  PMID: 20058208 RESULT

• Westwood JP, Webster H, McGuckin S, McDonald V, Machin SJ, Scully M. Rituximab for thrombotic thrombocytopenic purpura: benefit of early administration during acute episodes and use of prophylaxis to prevent relapse. J Thromb Haemost. 2013 Mar;11(3):481-90. doi: 10.1111/jth.12114.

  PMID: 23279219 RESULT

• Ahmad A, Aggarwal A, Sharma D, Dave HP, Kinsella V, Rick ME, Schechter GP. Rituximab for treatment of refractory/relapsing thrombotic thrombocytopenic purpura (TTP). Am J Hematol. 2004 Oct;77(2):171-6. doi: 10.1002/ajh.20166.

  PMID: 15389904 RESULT

• Chemnitz J, Draube A, Scheid C, Staib P, Schulz A, Diehl V, Sohngen D. Successful treatment of severe thrombotic thrombocytopenic purpura with the monoclonal antibody rituximab. Am J Hematol. 2002 Oct;71(2):105-8. doi: 10.1002/ajh.10204.

  PMID: 12353309 RESULT

MeSH Terms

Conditions

Purpura, Thrombotic Thrombocytopenic

Interventions

Rituximab

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

Results Point of Contact

• Title: Dr. Elaine Majerus
• Organization: Washington University

emajerus@wustl.edu

314-362-8866

Study Officials

• Elaine M Majerus, MD, PhD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2012
• First Posted: March 15, 2012
• Study Start: August 1, 2012
• Primary Completion: February 14, 2020
• Study Completion: February 14, 2020
• Last Updated: August 17, 2021
• Results First Posted: August 13, 2021

Record last verified: 2021-08

Locations

US (4)