Please select the eligibility criteria that correspond to the clinical trial below.
Title: Allogeneic Bone Marrow Derived Mesenchymal Stem Cells for the Treatment of Fistulas in Patients With Refractory Perianal Crohn's Disease
Brief Summary: In a dose escalation study we will determine the safety and preliminary efficacy of allogeneic bone marrow mesenchymal stem cells (bmMSCs) in the induction of response for active fistulizing Crohn's Disease (CD).


Options:
A: Inclusion Criteria:

* Men and women \> 18 years of age
* Patient must have had CD (for at least 3 months from the time of initial diagnosis). The diagnosis of CD must have been confirmed by endoscopic and histologic evidence
* CDAI score of \<250 at screening and baseline
* Peri-anal fistulas must be refractory to conventional medical therapy Which means that at some time during the course of the disease, patient must have received both steroids and immunosuppressive agents (for example, azathioprine, 6-mercaptopurine (6-MP), methotrexate, or infliximab) which did not result in an adequate response to treatment
* Patients with previous surgical attempts to eradicate perianal fistulas are eligible for inclusion as are patients with setons in situ. Setons will be removed during the surgical procedure
* Patients included in the study might be receiving 5-aminosalicylic acid (5-ASA), steroids, azathioprine, 6-MP, methotrexate, or any similar drug at the time of enrolment and is allowed to have a history of infliximab treatment, provided the following conditions are fulfilled at screening:
* The dose of 5-ASA (both oral and rectal) must have been stable for at least 4 weeks prior to enrollment
* The dose of steroids must be stable for at least 4 weeks prior to enrollment
* The dose of immunosuppressants (for example azathioprine, 6-MP, or methotrexate) must have been stable for at least 8 weeks prior to enrollment and the patient on therapy for at least three months prior to enrollment
* The last dose of infliximab or other anti-TNF drug is \> 8 weeks prior to enrollment
* No need for immediate surgery (obstruction, strictures or abscess)
* If female and of child-bearing age, patient must be non-pregnant non-breastfeeding, and use adequate contraception
* Patient is willing to participate in the study and has signed the informed consent. Consent must be obtained prior to any study procedure

Exclusion Criteria:

* Patients with evidence of acute peri-anal infection, presence of peri-anal abscesses larger than 2 cm, and anal or rectal stricture
* Patients with evidence of any infections needing antibiotic treatment
* Rectovaginal fistulas, or complex peri-anal fistulas with more than two internal openings
* Patients suffering from renal- or hepatic failure
* Use of any investigational drug within 1 month prior to screening or within 5 half-lives of the investigational agent, whichever is longer
* Patient is allergic to gadolinium (MRI contrast agent)
* Patient with severe renal insufficiency defined as patients with a glomerular filtration rate (GFR) below 60 mL/min/1.73 m2. GFR = 186.3 x (serum creatinine)-1.154 x (age in years)-0.203 x 1.212 (if patient is black) x 0.742 (if female)
* Due to the high strength electromagnetic fields that will be used during MRI there is a risk of interference with any metallic implants in the body. The following conditions will disqualify patients from having an MRI and will be excluded from this study:

  * Electronically, magnetically, and mechanically activated implants
  * Ferromagnetic or electronically operated stapedial implants
  * Cardiac pacemakers/carotid sinus pacemaker implant
  * Hemostatic clips
  * Metallic splinters in the orbit
  * Insulin pumps and nerve stimulators
  * Lead wires or similar wires
  * Metal intrauterine device
* Change in concomitant medication:

  * Steroids must be stable for at least 4 weeks prior to enrollment
  * 5-ASA should be on a stable dose \> 4 weeks prior to enrollment
  * Immunosuppressants (e.g. azathioprine, 6MP or methotrexate) should be on a stable dose \> 8 weeks prior to enrolment
  * Infliximab or other anti-TNF antibody therapy should not be administered \< 8 weeks prior to enrollment
* Claustrophobia
* Documented HIV (Human Immunodeficiency Virus) infection. Active hepatitis B, hepatitis C or TB
* Patients who currently have or who have had an opportunistic infection (e.g., herpes zoster \[shingles\], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 6 months prior to screening
* Serious infections (such as pneumonia or pyelonephritis) in the previous 3 months. Less serious infections (such as acute upper respiratory tract infection \[colds\] or simple urinary tract infection) need not be considered exclusions at the discretion of the investigator
* Malignancy within the past 5 years (except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence)
* History of lymphoproliferative disease including lymphoma
* Patient is unwilling or unable to comply with the study procedures
B: 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.
C: Inclusion Criteria:

1. Age 18 to 80
2. Diagnosis of moderately to severely active Crohn's disease (CD)
3. CD involvement of the ileum and/or colon
4. Demonstrated, over the previous 5 year period, an inadequate response to, loss of response to, or intolerance of at least 1 of the following agents, within protocol-specified parameters:

   1. Immunomodulators
   2. Tumor necrosis factor-alpha (TNFα) antagonists
   3. Corticosteroids
5. May be receiving a therapeutic dose of conventional therapies for irritable bowel disease (IBD) defined by the protocol

Exclusion Criteria

1. Evidence of abdominal abscess at the initial screening visit, other than a minimum of 10 aphthous ulcerations involving a minimum of 10 contiguous cm of intestine
2. Extensive colonic resection, subtotal or total colectomy
3. History of \>3 small bowel resections or diagnosis of short bowel syndrome
4. Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine
5. Have received non permitted IBD therapies within either 30 or 60 days, depending on the medication, as stated in the protocol
6. Chronic hepatitis B or C infection
7. Active or latent tuberculosis
D: Inclusion Criteria

1. Men and Women 18-75 years of age with a diagnosis of Crohn's disease for at least six months duration.
2. Single and Multi-tract Perianal fistula, with or without previous failed surgical repair.
3. Have no contraindications to MR evaluations: e.g. pacemaker or magnetically active metal fragments, claustrophobia
4. Ability to comply with protocol
5. Competent and able to provide written informed consent
6. Concurrent Crohn's-related therapies with stable doses (\>2 months) corticosteroids, 5- ASA drugs, immunomodulators, anti-TNF therapy, anti-integrin and anti-interleukin therapies are permitted

Exclusion Criteria

1. Inability to give informed consent.
2. Clinically significant medical conditions within the six months before administration of MSCs: e.g. myocardial infarction, active angina, congestive heart failure or other conditions that would, in the opinion of the investigators, compromise the safety of the subject.
3. Specific exclusions:

   1. Hepatitis B or C
   2. HIV
   3. Abnormal AST or ALT at screening(defined as \>/= 2x ULN)
4. History of cancer including melanoma (with the exception of localized skin cancers) within one year of screening.
5. History of colorectal cancer within 5 years
6. Investigational drug within one month of treatment
7. Pregnant or breast feeding or trying to become pregnant.
8. Presence of a rectovaginal or perineal body fistula
9. Change in Crohn's immunosuppressive regimen within the 2 months prior to enrollment
10. Uncontrolled intestinal Crohn's disease which will require escalation for medical therapy or surgery within 2 months of enrollment
11. Severe anal canal disease that is stenotic and requires dilation
12. Female participant unwilling to agree to use acceptable contraception methods during participation in study

Answer: A