Status:
COMPLETED
Cyclophosphamide and Rabbit Antithymocyte Globulin (rATG)/Rituximab in Patients With Systemic Lupus Erythematosus
Lead Sponsor:
Northwestern University
Conditions:
Systemic Lupus Erythematosus
Eligibility:
All Genders
15-60 years
Phase:
PHASE2
Brief Summary
This study is designed to examine whether treating patients with lupus with high dose cyclophosphamide together with rATG/rituximab (drugs which reduce the function of the immune system), followed by ...
Detailed Description
Mobilization Participants will be administered Cyclophosphamide at 2.0 g/m2 in 200 ml of normal saline (NS) over 1 hour. Hydration with 0.9 NS at approximately 100-250-ml/ hour will begin 4 hours prio...
Eligibility Criteria
Inclusion
- Ages 15 to 60 years old
- Meet at least 4 of 11 American College of Rheumatology (ACR) Classification criteria for systemic lupus erythematosus (SLE) (see Appendix 16.2)
- Meet one of following five:
- For lupus nephritis, participants must fail pulse cyclophosphamide (500 to 1000 mg/m2 monthly for a minimum of 6 months). Failure is defined as meeting criteria to be considered as BILAG renal category A.
- For visceral organ involvement other than nephritis, participants must be BILAG cardiovascular/respiratory category A, vasculitis category A, or neurologic category A and must fail at least 3 months of oral or IV cyclophosphamide and be corticosteroid dependent. Steroid dependence being defined as at least 3 months of steroid therapy and inability to wean corticosteroid to less than 20 mg/day of prednisone or equivalent.
- For cytopenias that are immune mediated, participants must be BILAG hematologic category A. Participants must fail corticosteroids (either oral prednisone \> 0.5 mg/kg/day for more than 6 months or pulse methylprednisolone for at least one cycle of three days), and at least one of the following: azathioprine at 2 mg/kg/day for at least 3 months, mycophenolate mofetil 2 grams daily for more than 3 months, cyclophosphamide intravenously or orally for at least 3 months, or cyclosporine at least 3 mg/kg/day for at least 3 months, danazol for at least 3 months, or splenectomy.
- For mucocutaneous disease, participants must meet BILAG mucocutaneous category A, be unable to be weaned from prednisone to less than 0.5 mg/kg/day for more than 6 months and obvious cushingoid habitus, and have received at least one of the following: azathioprine at 2 mg/kg/day for at least 3 months, methotrexate at 15mg/week for at least 3 months, cyclophosphamide intravenously or orally for at least 3 months, or cyclosporine at least 3 mg/kg/day for at least 3 months.
- For arthritis/myositis, participants must meet BILAG musculoskeletal category A, be unable to be weaned from prednisone to less than 0.5 mg/kg/day for more than 6 months and obvious cushingoid habitus, and have received at least one of the following: azathioprine at 2 mg/kg/day for at least 3 months, methotrexate at 15mg/ week for at least 3 months, cyclophosphamide intravenously or orally for at least 3 months, or cyclosporine at least 3 mg/kg/day for at least 3 months.
- Able to give informed consent.
- If indication for hematopoietic stem cell transplant (HSCT) is nephritis, a renal biopsy must demonstrate the potential of a reversible (non-fibrotic) component indicating that if successful the participant would not be likely to be permanently dialysis-dependent after transplant.
- Since the BILAG is only one of multiple indices for SLE, patients may also be candidates if despite prior immune suppression therapy as described above, patients are still on active immune suppression (more than 10mg a day of prednisone).
- Patients with SLE whose major manifestation is Antiphospholipid syndrome (APS) may be candidates without prior immune suppression therapy if they have had a visceral organ thrombotic or embolic event despite anticoagulation.
- Patients with SLE whose major manifestation is Antiphospholipid syndrome (APS) may be candidates without prior immune suppression therapy if they have had a visceral organ thrombotic or embolic event despite anticoagulation.
Exclusion
- HIV positive
- Ongoing malignancy except localized basal cell or squamous skin cancer. Other malignancies for which the participant is judged to be cured by local surgical therapy, such as head and neck cancer, or stage I or II breast cancer will be considered on an individual basis by the investigators doing the final screening for participant qualification.
- Positive pregnancy test, inability or unwillingness to pursue effective means of birth control, failure to willingly accept or comprehend irreversible sterility as a side effect of therapy.
- Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible.
- Diffusing capacity of lung for carbon monoxide (DLCO) \< 45% of predicted unless attributed to active lupus.
- Resting left ventricular ejection fraction (LVEF) \< 40% unless attributed to active lupus.
- Known hypersensitivity to E Coli derived proteins.
- Transaminases greater than 2 times normal unless attributed to active lupus.
- Positive tuberculosis skin test
- Any active infection
- Any co-morbid illness that in the opinion of the investigator would jeopardize the ability of the subject to tolerate the study.
- Failure to collect at least 2.0 x 106 cluster of differentiation 34 (CD34+) cells/kg
- Antinuclear antibody (ANA)-negative
Key Trial Info
Start Date :
September 23 2005
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
May 1 2019
Estimated Enrollment :
32 Patients enrolled
Trial Details
Trial ID
NCT00278538
Start Date
September 23 2005
End Date
May 1 2019
Last Update
February 28 2020
Active Locations (2)
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1
Northwestern University, Feinberg School of Medicine
Chicago, Illinois, United States, 60611
2
Northwestern University
Chicago, Illinois, United States, 60611