
    too difficult to recruit given new crohn's medications approved
  
["crohn's disease", 'crohn disease']
['high-dose cyclophosphamide']

        Inclusion Criteria:

          -  ≥ 18 years of age, males and females will be eligible

          -  Moderate to severe Crohn's Disease (CD) with CDAI > 220, in addition to evidence of
             ulceration on ileocolonoscopy or active disease on small bowel imaging (in patients
             with an ostomy, CDAI criteria do not apply)

          -  Disease progression (primary or secondary non-responder, or reaction to) to at least
             one anti-tumor necrosis factor (TNF) agent (infliximab, adalimumab, certolizumab
             pegol), and additionally had disease progression despite one of the following
             immunosuppressant drugs: azathioprine, 6-mercaptopurine, methotrexate, cyclosporine,
             natalizumab, vedolizumab

          -  Willingness to participate in a clinical trial

          -  Approval by Enrollment Panel, who will collectively decide on the appropriateness of
             possible study study participants

        Exclusion Criteria:

          -  Pregnant or nursing women

          -  Sexually active men and women who do not agree to use effective means of birth control
             during treatment period

          -  Evidence of primarily fibrostenosing disease without active inflammatory disease on
             disease staging

          -  Co-morbid conditions including cardiac disease with an ejection fraction of < 45%,
             chronic renal failure with serum creatinine > 2.0, liver disease with total bilirubin
             > 2.0, (excluding hyperbilirubinemia secondary to Gilbert's disease) or transaminitis
             > 3x upper limit of normal.

          -  History of serious allergic reaction to cyclophosphamide

          -  History of malignancy in the last 5 years (excluding non-melanomatous skin cancers)

          -  Patients who are pre-terminal

          -  Toxic megacolon

          -  Active infection

          -  White blood cell count < 3000 cells/ul, platelets < 100K / ul, hemoglobin < 10.0 g/dL

          -  Any use of thiopurines, methotrexate or anti-TNF agents in the previous four weeks
             prior to treatment
      