Low Dose Rituximab in Thrombotic Thrombocytopenic Purpura

Thrombotic Thrombocytopenic Purpura Clinical Trial

Official title:

Adjuvant Low Dose Rituximab for Acquired TTP With Severe ADAMTS13 Deficiency

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01554514
• Other study ID #: 201108256-LDrituximab
• Secondary ID: 1U54HL112303-01
• Status: Completed
• Phase: Phase 2
• Start date: August 2012
• Est. completion date: February 14, 2020

Study information

• Verified date: August 2021
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: February 14, 2020
• Est. primary completion date: February 14, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 >1 x ULN

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

Related Conditions & MeSH terms

• Purpura
• Purpura, Thrombocytopenic
• Purpura, Thrombotic Thrombocytopenic
• Thrombotic Thrombocytopenic Purpura

Intervention

Biological:
• rituximab
rituximab intravenously 100 mg every week for four doses

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Duke University Medical Center	Durham	North Carolina
United States	Washington University	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View Citation

Chemnitz J, Draube A, Scheid C, Staib P, Schulz A, Diehl V, Söhngen D. Successful treatment of severe thrombotic thrombocytopenic purpura with the monoclonal antibody rituximab. Am J Hematol. 2002 Oct;71(2):105-8. — View Citation

Froissart A, Buffet M, Veyradier A, Poullin P, Provôt 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. — View Citation

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

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):481-9 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Incidence of Durable Treatment Response	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 and includes those with exacerbations	60 days
Secondary	Number of Days to Durable Treatment Response	Median time to treatment response	60 days
Secondary	Incidence of Relapse	Relapse is recurring TTP >30 days after Treatment Response	Between 30 days and 2 years
Secondary	Months to Relapse	Mean months to relapse	2 years
Secondary	Incidence of Death	Incidence of death will be assessed at 4 weeks, 1 year and 2 years	2 years
Secondary	Treatment-related Adverse Events	Incidence, type and severity of treatment-related adverse events will be assessed. Patient reports, lab values, and physical exam were used to identify treatment-related adverse events.	2 years