Please select the eligibility criteria that correspond to the clinical trial below.
Title: Cyclophosphamide and rATG/Rituximab in Patients With Systemic Lupus Erythematosus: Phase II Trial
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 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.


Options:
A: Inclusion Criteria:

1. Patient with a complex perianal fistula. A complex perianal fistula must meet one of the following:

   * No fistula tract is palpated under the perianal skin or tract parallel to the rectum on examination with a stylet.
   * Associated anal incontinence in transsphincteric fistulas.
   * Risk factors for anal incontinence.
   * At least one prior surgery for a fistulous disease.
   * Suprasphincteric tracts shown by an image test.
2. Women of childbearing age should have a negative serum or urine pregnancy test (sensitive to 25IU of hCG) and not be lactating before study entry. Both men and women should use adequate birth control methods as defined by the investigator.
3. Seton presence is allowed at the time of study entry and until cells (in groups receiving ASCs) or Fibrin adhesive are implanted.
4. No condition that may prevent the patient from following the study procedures until 26 weeks of follow-up are completed is foreseen.
5. Patient should give his/her signed, written informed consent. -

Exclusion Criteria:

1. Patient has been diagnosed with IBD
2. Patient has a rectovaginal fistula
3. Patient is pregnant or lactating woman
4. Patient has acute sepsis at the time of study entry
5. A liposuction to draw at least 100 cc of fat from the abdominal wall is not technically feasible.
6. Patient needs surgery in the perianal region for reasons other than fistulas
7. Presence of two or more complex perianal fistulas
8. Patient has collections \> 2 cm in MRI. If such collections exist, the surgeon may perform a complete toilette of the area.
9. Patient is allergic to local anesthetics or Gadolinium (MRI contrast agent).
10. MRI is not technically feasible.
11. Patient has abused alcohol or other addictive substances within 6 months of study entry.
12. Patient has active or latent infection by HIV, HBV or HCV.
13. Patient has undergone major surgery or sustained a severe trauma, in the investigator's judgment, within 28 days of recruitment.
14. Patient is receiving or has received immunomodulatory treatment for reasons other than the fistula within 6 months of study entry.
15. Patient has a malignant tumour, except for basal or squamous cell carcinoma of the skin, or has a prior history of a malignant tumour, except if the tumour has been in remission for at least the past 5 years.

    -
B: 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
C: Inclusion Criteria:

Inclusion criteria: mandatory

1. Age between 18 and 50 years (Patients aged 50-65 can participate if specially approved by the Trial Steering Committee)
2. Confirmed diagnosis of active Crohn's Disease
3. Unsatisfactory course despite 3 immunosuppressive agents (usually azathioprine, methotrexate and infliximab) in addition to corticosteroids. Patients should have relapsing disease (i.e. \>1 exacerbation/year) despite thiopurines, methotrexate and/or infliximab maintenance therapy or clear demonstration of intolerance / toxicity to these drugs.
4. Impaired function and quality of life, compared to population means, on at least one of the following:

   1. IBDQ (Appendix 6)
   2. European Questionnaire of Life quality (EuroQOL-5D, Appendix 4)
   3. Impaired function on Karnofsky index (Appendix 7)
5. Current problems unsuitable for surgery and patient at risk for developing short bowel syndrome.
6. Informed consent

Inclusion criteria: discretionary

1. Wherever possible, diseased tissue should be accessible endoscopically for objective histological study but in the case of small bowel disease that is extensive but does not extend to duodenum or terminal ileum, participation without endoscopy is allowed.
2. Smokers may enter the study provided they have received intensive counselling about smoking.
3. Add patients with ileostomy/colostomy and patients with short bowel syndrome

Exclusion Criteria:

1. Pregnancy or unwillingness to use adequate contraception during the study
2. Concomitant severe disease
3. Diarrhoea due to short small or large bowel
4. Infection or risk thereof
5. Significant malnutrition: Body Mass Index (BMI) ≤18, serum albumin \<20 g/l
6. Previous poor compliance
7. Concurrent enrolment in any other protocol using an investigational drug or hematopoietic growth factor up to four weeks before study entry.
8. Lack of funding
D: Inclusion Criteria:

* Colonic or small bowel Crohn's disease based on endoscopic appearances and histology
* Refractory to induction with infliximab or adalimumab; or have lost response to these agents; or have had side effects precluding their further use
* Where there has been loss of response to one of these agents, the other must be tried before being eligible
* Crohn's disease activity score (CDAI) 250 or more.
* C-reactive protein \>10mg/L
* Surgery must have been offered to the subject (if appropriate) and declined
* Signed informed consent

Exclusion Criteria:

* Active sepsis, perforating disease. Coexistent perianal fistulous disease is permitted, providing no co-existent infection within previous 4 weeks
* Chronic stricturing disease in isolation
* Coexistent CMV disease
* Prior history of malignancy
* Pregnant or unwilling to practice contraceptive therapy or breast feeding females
* Last biologic therapy must be greater than 4 weeks prior, must be on stable corticosteroid dose for 14 days prior, during therapy and for 14 days after therapy, must be on stable immunomodulator dose (eg, azathioprine) for 14 days prior, during therapy and for 14 days after.

Answer: B