Cyclophosphamide and Rabbit Antithymocyte Globulin (rATG)/Rituximab in Patients With Systemic Lupus Erythematosus
Condition: Systemic Lupus Erythematosus
MeSH terms: Lupus Erythematosus, Systemic
Intervention: Hematopoietic stem cell transplantation
Intervention description: Autologous hematopoietic stem cell transplantation
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 15 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Stem cell, Autoimmune disease, Systemic Lupus Erythematosus

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 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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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:

               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 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 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.

          -  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