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A Pilot Study of Rituximab for the Anticoagulation Resistant Manifestations of Antiphospholipid Syndrome (RITAPS)

Primary Purpose

Antiphospholipid Syndrome

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Rituximab
Sponsored by
Hospital for Special Surgery, New York
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Antiphospholipid Syndrome focused on measuring antiphospholipid syndrome

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • - Positive aPL profile defined as:

    • Positive lupus anticoagulant test as defined by the International Society on Thrombosis and Haemostasis, on two or more occasions, at least 12 weeks apart and/or
    • Positive anticardiolipin antibody (aCL) immunoglobulin G(Ig)G/M/A isotype, present in > 40U, on two or more occasions, at least 12 weeks apart and/or
    • Positive anti-β2-glycoprotein-I (aβ2GPI) IgG/M/A isotype, present in > 40U, on two or more occasions, at least 12 weeks apart

AND

- Clinical features attributable to aPL that are resistant to warfarin and/or heparin:

  • Persistent thrombocytopenia and/or
  • Persistent autoimmune hemolytic anemia and/or
  • Cardiac valve disease and/or
  • Chronic skin ulcers and/or
  • Renal thrombotic microangiopathy and/or
  • Cognitive dysfunction with/without white matter changes

Exclusion Criteria (selected):

  • > 4/11 American College of Rheumatology Classification Criteria for SLE
  • Acute thrombosis
  • History of stroke (only for patients with cognitive dysfunction)
  • Positive Hepatitis B or C serology
  • History of positive HIV
  • Acute or chronic pancreatitis
  • Treatment with any investigational agent within 4 weeks of screening
  • Receipt of a live vaccine within 4 weeks prior to randomization
  • Previous Treatment with Rituximab (MabThera® / Rituxan®)
  • Previous treatment with Natalizumab (Tysabri®)
  • Known active bacterial, viral fungal mycobacterial, or other infection
  • Pregnancy
  • Concomitant malignancies or previous malignancies, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
  • History of psychiatric disorder that would interfere with normal participation in this protocol
  • Significant cardiac or pulmonary disease

Sites / Locations

  • Barbara Volcker Center for Women and Rheumatic Disease, Hospital for Special Surgery

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Rituximab

Arm Description

All patients will receive 1000 milligrams of rituximab by intravenous infusion on Days 1 and 15.

Outcomes

Primary Outcome Measures

Number of Participants Experiencing Serious and Non Serious Adverse Events
Serious and non-serious adverse events were evaluated throughout 52 weeks + additional 4 months for the patients with low B cell counts.

Secondary Outcome Measures

The Efficacy of Rituximab
Outcome measures scored as complete response(CR),partial(PR),and none(NR) at 24 weeks.For thrombocytopenia,CR defined as a platelet count of ≥150×109/μl,PR as 100-149,and NR as <100.For CVD,CR defined as the disappearance of cardiac lesions,PR as 50%improvement,and NR as no change.For skin ulcer,CR defined as disappearance,PR as 50% improvement,and NR as no change.For aPL nephropathy,CR defined as a normal serum creatinine level,inactive urinary sediment,and urinary protein:creatinine 0.5;PR as a serum cr level 15%above baseline,RBCs per high-power field 50%above baseline with no casts,50%improvement in the urinary prt:cr,and estimated GFR 10%above baseline;and NR as the absence of C/PR.For cognitive dysfunction,CR defined as normalization of the cognitive impairment index with 50%improvement,PR as abnormal index with 50%,and NR as no change.

Full Information

First Posted
September 28, 2007
Last Updated
October 2, 2017
Sponsor
Hospital for Special Surgery, New York
Collaborators
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00537290
Brief Title
A Pilot Study of Rituximab for the Anticoagulation Resistant Manifestations of Antiphospholipid Syndrome
Acronym
RITAPS
Official Title
A Pilot Study of Rituximab for the Anticoagulation Resistant Manifestations of Antiphospholipid Syndrome (RITAPS)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
September 2007 (undefined)
Primary Completion Date
January 2013 (Actual)
Study Completion Date
January 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospital for Special Surgery, New York
Collaborators
Genentech, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RITuximab AntiphosPholipid Syndrome (RITAPS) Study is designed to evaluate whether a medication called rituximab would reduce the signs and symptoms of antiphospholipid antibody (aPL) -related certain clinical problems.
Detailed Description
Persistently antiphospholipid antibody (aPL)-positive patients, age 18 - 75 years of age, with anticoagulation-resistant manifestations of APS and fulfilling protocol defined study inclusion criteria will receive two doses of Rituximab, and will be followed for 6 and 12 months for clinical and safety outcomes, respectively. Patients are eligible to take part in this study if their blood test is persistently positive for aPL and they have one or more of the aPL-related clinical problem(s) listed below: low platelet (blood cells involved in the prevention of bleeding) count; anemia (deficiency of red blood cells); heart valve disease; skin ulcers; kidney smal vessel blood clots; and/or memory problems.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Antiphospholipid Syndrome
Keywords
antiphospholipid syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Rituximab
Arm Type
Experimental
Arm Description
All patients will receive 1000 milligrams of rituximab by intravenous infusion on Days 1 and 15.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
Rituximab 1000mg IV on Days 0 and 15
Primary Outcome Measure Information:
Title
Number of Participants Experiencing Serious and Non Serious Adverse Events
Description
Serious and non-serious adverse events were evaluated throughout 52 weeks + additional 4 months for the patients with low B cell counts.
Time Frame
52 weeks + additional 4 months if needed
Secondary Outcome Measure Information:
Title
The Efficacy of Rituximab
Description
Outcome measures scored as complete response(CR),partial(PR),and none(NR) at 24 weeks.For thrombocytopenia,CR defined as a platelet count of ≥150×109/μl,PR as 100-149,and NR as <100.For CVD,CR defined as the disappearance of cardiac lesions,PR as 50%improvement,and NR as no change.For skin ulcer,CR defined as disappearance,PR as 50% improvement,and NR as no change.For aPL nephropathy,CR defined as a normal serum creatinine level,inactive urinary sediment,and urinary protein:creatinine 0.5;PR as a serum cr level 15%above baseline,RBCs per high-power field 50%above baseline with no casts,50%improvement in the urinary prt:cr,and estimated GFR 10%above baseline;and NR as the absence of C/PR.For cognitive dysfunction,CR defined as normalization of the cognitive impairment index with 50%improvement,PR as abnormal index with 50%,and NR as no change.
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: - Positive aPL profile defined as: Positive lupus anticoagulant test as defined by the International Society on Thrombosis and Haemostasis, on two or more occasions, at least 12 weeks apart and/or Positive anticardiolipin antibody (aCL) immunoglobulin G(Ig)G/M/A isotype, present in > 40U, on two or more occasions, at least 12 weeks apart and/or Positive anti-β2-glycoprotein-I (aβ2GPI) IgG/M/A isotype, present in > 40U, on two or more occasions, at least 12 weeks apart AND - Clinical features attributable to aPL that are resistant to warfarin and/or heparin: Persistent thrombocytopenia and/or Persistent autoimmune hemolytic anemia and/or Cardiac valve disease and/or Chronic skin ulcers and/or Renal thrombotic microangiopathy and/or Cognitive dysfunction with/without white matter changes Exclusion Criteria (selected): > 4/11 American College of Rheumatology Classification Criteria for SLE Acute thrombosis History of stroke (only for patients with cognitive dysfunction) Positive Hepatitis B or C serology History of positive HIV Acute or chronic pancreatitis Treatment with any investigational agent within 4 weeks of screening Receipt of a live vaccine within 4 weeks prior to randomization Previous Treatment with Rituximab (MabThera® / Rituxan®) Previous treatment with Natalizumab (Tysabri®) Known active bacterial, viral fungal mycobacterial, or other infection Pregnancy Concomitant malignancies or previous malignancies, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix History of psychiatric disorder that would interfere with normal participation in this protocol Significant cardiac or pulmonary disease
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Doruk Erkan, MD
Organizational Affiliation
Hospital for Special Surgery, New York
Official's Role
Principal Investigator
Facility Information:
Facility Name
Barbara Volcker Center for Women and Rheumatic Disease, Hospital for Special Surgery
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
23124321
Citation
Erkan D, Vega J, Ramon G, Kozora E, Lockshin MD. A pilot open-label phase II trial of rituximab for non-criteria manifestations of antiphospholipid syndrome. Arthritis Rheum. 2013 Feb;65(2):464-71. doi: 10.1002/art.37759.
Results Reference
result
PubMed Identifier
22269862
Citation
Khattri S, Zandman-Goddard G, Peeva E. B-cell directed therapies in antiphospholipid antibody syndrome--new directions based on murine and human data. Autoimmun Rev. 2012 Aug;11(10):717-22. doi: 10.1016/j.autrev.2011.12.011. Epub 2012 Jan 16.
Results Reference
derived
Links:
URL
http://www.hss.edu/clinical-trials-directory.asp
Description
Hospital for Special Surgery Clinical Trials List
URL
http://www.hss.edu/barbara-volcker.asp
Description
Barbara Volcker Center for Women and Rheumatic Disease

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A Pilot Study of Rituximab for the Anticoagulation Resistant Manifestations of Antiphospholipid Syndrome

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