Low Dose Rituximab in Thrombotic Thrombocytopenic Purpura

ID: NCT01554514
Status: Recruiting
Phase: Phase 2
Start Date: August 01, 2012
First Submitted: March 08, 2012
Last Updated: February 22, 2018
Results: N/A
Sponsors & Collaborators: J. Evan Sadler, M.D., Ph.D., National Heart, Lung, and Blood Institute (NHLBI)
Location: United States
Conditions: Thrombotic Thrombocytopenic Purpura
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Study Description

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.

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.
Condition or disease Intervention/treatment Phase

Thrombotic Thrombocytopenic Purpura

Biological: rituximab
Other Names
Rituxan
Phase 2

Tracking Information

First Submitted DateMarch 08, 2012
Last Update Posted DateFebruary 22, 2018
Start DateAugust 01, 2012
Anticipated Completion DateDecember 01, 2019
Primary Completion DateDecember 01, 2018
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Incidence of the composite primary outcome of exacerbation or refractory TTP [Time Frame: 60 days]

    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.

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Incidence of Durable Treatment Response [Time Frame: 60 days]

    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]

  • Incidence of Relapse [Time Frame: 2 years]

    Relapse is recurring TTP >30 days after Treatment Response

  • Number of days to Relapse [Time Frame: 2 years]

  • Incidence of death [Time Frame: 2 years]

    Incidence of death will be assessed at 4 weeks, 1 year and 2 years

  • Treatment-related adverse events [Time Frame: 2 years]

    Incidence, type and severity of treatment-related adverse events will be assessed

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleLow Dose Rituximab in Thrombotic Thrombocytopenic Purpura
Official TitleAdjuvant Low Dose Rituximab for Acquired TTP With Severe ADAMTS13 Deficiency
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.

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.

Study TypeInterventional
Study PhasePhase 2
Estimated Enrollment
20
Allocation
Not Available
Interventional Model
Single Group Assignment
Masking
None (Open Label)
Primary Purpose
Treatment
Conditions
Thrombotic Thrombocytopenic Purpura
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Biological: rituximab

rituximab intravenously 100 mg every week for four doses

Other Names
Rituxan
Study Groups/Cohorts
low dose rituximab
this is a single-arm trial

Study Arms
Experimental low dose rituximab
this is a single-arm trial
Biological : rituximab
rituximab intravenously 100 mg every week for four doses

Arm Intervention/Treatment
Experimental low dose rituximab
this is a single-arm trial
Biological : rituximab

Recruitment Information

Recruitment Status:Recruiting
Enrollment20
Completion DateDecember 01, 2019
Eligibility Criteria: 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
GenderAll
Age18 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Not Available
Listed Location Countries
United States

Administrative Information

NCT Number:NCT01554514
Other Study ID Numbers
LDrituximab
1U54HL112303-01
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible PartyJ. Evan Sadler, M.D., Ph.D., Washington University
Study Sponsor
J. Evan Sadler, M.D., Ph.D.
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator
J E Sadler, MD, PhD
Washington University School of Medicine