Cyclophosphamide and rATG/Rituximab in Patients With Systemic Lupus Erythematosus

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Northwestern University
Sponsor:
Information provided by (Responsible Party):
Richard Burt, MD, Northwestern University
ClinicalTrials.gov Identifier:
NCT00278538
First received: January 15, 2006
Last updated: February 4, 2014
Last verified: February 2014
  Purpose

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 return of their previously collected stem cells will result in improvement in the disease. Stem cells are undeveloped cells that have the capacity to grow into mature blood cells, which normally circulate in the blood stream. The purpose of the intense chemotherapy is to destroy the cells in the immune system which may be causing this disease. The purpose of the stem cell infusion is to produce a normal immune system that will no longer attack body. The study purpose is to examine whether this treatment will result in improvement in the lupus disease.


Condition Intervention Phase
Systemic Lupus Erythematosus
Biological: Hematopoietic stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Cyclophosphamide and rATG/Rituximab in Patients With Systemic Lupus Erythematosus: Phase II Trial

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • The primary efficacy outcome is overall survival and the proportion of participants who achieve and maintain remission after transplant. [ Time Frame: 5 years after transplant ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: August 2005
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: hematopoietic stem cell transplantation
Autologous hematopoietic stem cell transplantation will be performed
Biological: Hematopoietic stem cell transplantation
Autologous hematopoietic stem cell transplantation

  Eligibility

Ages Eligible for Study:   15 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ages 15 to 60 years old
  • Meet at least 4 of 11 American College of Rheumatology (ACR) Classification criteria for SLE (see Appendix 16.2)
  • Meet one of following five:

    1. 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.
    2. 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.
    3. 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.
    4. 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.
    5. 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 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

Exclusion Criteria:

  • 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.
  • DLCO < 45% of predicted unless attributed to active lupus.
  • Resting 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 CD34+ cells/kg
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00278538

Contacts
Contact: Dzemila Spahovic, MD 312-695-4960 d-spahovic@northwestern.edu

Locations
United States, Illinois
Northwestern University, Feinberg School of Medicine Recruiting
Chicago, Illinois, United States, 60611
Principal Investigator: Richard Burt, MD         
Sub-Investigator: Kathleen Quigley, R.N         
Sub-Investigator: Kimberly Young, RN         
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Principal Investigator: Richard Burt, MD         
Sponsors and Collaborators
Northwestern University
Investigators
Principal Investigator: Richard Burt, MD Northwestern University
  More Information

No publications provided

Responsible Party: Richard Burt, MD, MD, Northwestern University
ClinicalTrials.gov Identifier: NCT00278538     History of Changes
Other Study ID Numbers: DI SLE.Auto2003
Study First Received: January 15, 2006
Last Updated: February 4, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Cyclophosphamide
Rituximab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on July 31, 2014