An Open-Label, Proof of Consent Study of Vorinostat for the Treatment of Mdoerate-to-Severe Crohn s Disease and Maintenance Therapy With Ustekinumab

* INCLUSION CRITERIA: Individuals with moderate-to-severe CD, UC, and CGD colitis who are not controlled by and refractory to standard therapy will be eligible for inclusion into this study if they meet the following criteria: 1. Are 18 to 65 years of age, inclusive, at enrollment date. 2. Have a diagnosis of CD, UC, or CGD colitis that has been endoscopically or radiographically confirmed. A colonoscopy will be required at baseline to document mucosal disease activity. SES-CD for CD and CGD colitis will be obtained with minimum score of 7 and MES for UC patients will be obtained with minimum score of 2. 3. Have active CD symptoms as defined by a CDAI score between 220 and 350, UC symptoms defined by a Mayo score of 6 to 10 (moderate) or 10 to 12 (severe), or CGD colitis symptoms defined as an HBI score of 8-16 (moderate) or \> 16 (severe), and demonstrate active symptoms as defined by continued weight loss, abdominal pain and/or diarrhea not controlled by standard therapy. 4. The participant must have active CD and UC symptoms (as noted above) and therefore have had an inadequate response to, loss of response to, or intolerance to at least 1 of the following agent groups in control of their disease (as defined below for each individual agent group: Corticosteroids or Immunomodulators or TNF-alpha antagonists or Anti-integrin antibodies or JAK inhibitors or IL-12p19 (IL-23) antagonists). No specific induction therapy or long-term treatment for CGD colitis patients has been defined; therefore all symptomatic patients will be evaluated for inclusion on individual basis. a. Corticosteroids i. Signs and symptoms of persistently active disease despite a history of at least one 4-week induction regimen that included a dose equivalent to prednisone \>=30 mg PO once daily (QD) for 2 weeks or intravenously (IV) for 1 week OR ii. One failed attempt to taper corticosteroids to below a dose equivalent to prednisone 10 mg PO QD or to taper to below a dose of 9 mg of budesonide OR iii. History of intolerance of corticosteroids at the discretion of the principal investigator (PI) (including but not limited to Cushing s syndrome, osteopenia/osteoporosis, hyperglycemia, insomnia, or infection) b. Immunomodulators i. Signs and symptoms of persistently active disease despite a history of at least one 12-week regimen of oral azathioprine (AZA) (\>= 2.5 mg/kg/Day) or 6-MP (\>= 1.5 mg/kg/Day) OR ii. Signs and symptoms of persistently active disease despite a history of at least one 12-week regimen of MTX (\>= 25 mg/week) OR iii. History of intolerance of at least one immunomodulator (including but not limited to nausea/vomiting leading to discontinuation, abdominal pain, pancreatitis, liver function test abnormalities, lymphopenia, thiopurine methyltransferase genetic mutation, or serious infection) c. TNF-alpha antagonists with signs and symptoms of persistently active disease despite a history of receiving infliximab, adalimumab, or certolizumab at a dose approved for the treatment of CD or UC and: i. Patient had an inadequate response after completing the full induction regimen, per approved product labeling ii. Responded initially but then lost response with continued therapy iii. Patient had a significant adverse event response which precluded further use including but not exclusion of infusion reaction, serum sickness and/or lupus-like rash. d. Anti-integrin antibodies: with signs and symptoms of persistently active disease despite a history of receiving an anti-integrin antibody agent (natalizumab or vedolizumab) at a dose approved for the treatment of CD or UC and: i. Patient had an inadequate response after completing the full induction regimen, per approved product labeling ii. Responded initially but then lost response with continued therapy iii. Patient had a significant adverse event response which precluded further use including but not exclusion of infusion reaction, serum sickness and/or lupus-like reaction. e. JAK inhibitor: with signs and symptoms of persistently active disease despite a history of receiving a JAK inhibitor (tofacitinib and ruxolitinib) at a dose approved for the treatment of CD or UC and: i. Patient had an inadequate response after completing the full induction regimen, per approved product labeling ii. Responded initially but then lost response with continued therapy iii. Patient had a significant adverse event response which precluded further use including but not exclusion of infusion reaction, serum sickness and/or lupus-like reaction. f. Anti-IL-12 p19 (IL-23) antibodies: with signs and symptoms of persistently active disease despite a history of receiving an anti-IL-12p19 (IL-23) antibody agent (Skyrizi and Tremfya) at a dose approved for the treatment of CD or UC and: i. Patient had an inadequate response after completing the full induction regimen, per approved product labeling ii. Responded initially but then lost response with continued therapy iii. Patient had a significant adverse event response which precluded further use including but not exclusion of infusion reaction, serum sickness and/or lupus-like reaction. 5. At the discretion of the PI, concomitant medications will be permitted if the following conditions are met prior to baseline assessment (Day-1): a. 5-aminosalicylic acid (ASA)-based compounds are permissible if: i. Oral 5-ASA-based compounds must be at a stable dose for at least 3 weeks prior to baseline or ii. Recently discontinued oral 5-ASA-based compounds must have been discontinued at least 3 weeks prior to baseline or iii. Rectal 5-ASA-based compounds are not permissible during the study and must have been discontinued at least 3 weeks prior to baseline. b. Corticosteroids (e.g., prednisone, budesonide) are permissible if: i. Oral corticosteroids must be at a prednisone-equivalent dose of \<= 40 mg/day, or 9 mg/day of budesonide, and have been at a stable dose for at least 3 weeks prior to baseline or ii. Discontinuation of oral corticosteroids must have been completed at least 3 weeks prior to baseline or iii. Parenteral (subcutaneous, intramuscular, or IV) or rectal corticosteroids are not permitted during the study and must not have been used within a 3- week period prior to baseline c. CD, UC, or CGD colitis-specific antibiotics are permissible if using an antibiotic for treatment of CD,UC, or CGD colitis (i.e., metronidazole, ciprofloxacin, rifaximin, ampicillin, sulfonamide and tetracycline) i. Participants must have been using the antibiotic for at least 3 weeks before baseline at a stable dose or ii. If not currently using a CD, UC, or CGD colitis-specific antibiotic, the stop date must have been at least 3 weeks prior to baseline. d. Immunomodulators are permissible if: i. Participants receiving chronic (i.e., \>= 12 weeks) treatment with AZA, 6- MP, or MTX prior to baseline must be on a stable dose for at least 6-8 weeks prior to baseline and must continue on this same dose during the study. OR ii. Participants who have discontinued therapy with AZA, 6-MP, or MTX must have stopped the medication at least 4 weeks prior to baseline. OR iii. Participants must not have received therapy with other known immunomodulators (e.g. cyclosporine, tacrolimus, sirolimus, pentoxifylline, or mycophenolate mofetil) or experimental agents (e.g. granulocyte- or macrophage colony stimulating factor) for at least 8 weeks or 5 half-lives of agent from baseline, whichever is longer. e. The use of Anti-TNF, Anti-integrin, JAK inhibitors, Anti-IL-12p19 (IL-23) therapy or other biological therapy listed below will not be permitted and the following washout period will be required in order for participant to be eligible: i. Three months washout prior to baseline for certolizumab or natalizumab. ii. Two months washout prior to baseline for adalimumab, infliximab, and vedolizumab, tofacitinib, ruxolitinib, Skyrizi and Tremfya. iii. 8-week washout prior to baseline for cyclosporine, pimecrolimus, tacrolimus, and any other systemic immunosuppressant. 6\. Participants must have a primary medical care provider. 7\. Male participants must agree to employ birth control measures to prevent pregnancy in female partners from start of treatment and continuing through 3 months post treatment. 8\. Females of childbearing potential must not be breast-feeding, possibly or actually pregnant, must not have had unprotected intercourse for one month prior to dosing, and must agree not to become pregnant beginning from enrollment in the study to at least 6 months after the end of treatment. Participants must remain completely abstinent of potentially reproductive sexual intercourse (e.g. due to a committed lifestyle) or to consistently use BOTH a barrier method with a spermicide (male or female condom) AND ALSO one of the below listed methods of birth control: 1. Continuous/daily hormonal methods including oral contraceptive pills, patch, implant/injection, etc. 2. Surgical sterilization of either partner, of sufficient duration to be effective, and NOT known to have failed. 3. Intrauterine device. EXCLUSION CRITERIA: Individuals who meet ANY of the following criteria will be excluded from participation in this study: 1. Presence of clinically significant systemic infection (e.g., chronic or acute infection, urinary tract infection, or upper respiratory tract infection) within three months of screening. 2. History or presence of recurrent or chronic infection (e.g., viral infection \[including hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV)\], bacterial infection, systemic fungal infection, or syphilis). 3. Positive for tuberculosis (TB) via QuantiFERON-Gold (QFT-G). Individuals who are known to have received the tuberculosis vaccine will be administered the QFT-G. Patients cannot have received tuberculosis vaccine within 12 months prior to start of study and cannot receive tuberculosis vaccine while on study or within 12 months from the time of conclusion of study participation. 4. Has a history of active tuberculosis (TB) or a chest x-ray (CXR) with findings suggestive of old TB infection including calcified nodular lesions, apical fibrosis, or pleural scarring), acute or chronic HBV, HCV, HIV, or opportunistic infections. 5. A conduction abnormality on baseline electrocardiogram (ECG) that in the opinion of a cardiologist, is deemed significant. 6. At the discretion of the principal investigator, off-label use of any small molecule therapeutics that are immune modulators (e.g., naltrexone) within 90 days of beginning screening or at any time during the last 30-days of the screening window. 7. Presence of abnormal hematological and biochemical parameters, including: * Neutrophil count \< 1500 cells/mm3 * Hemoglobin \< 9 g/dL * Platelet count \<= 150,000 cells/mm3 * Creatinine \>= 1.2 times the upper limit of normal (ULN) * Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \>= 1.5 times ULN * Prothrombin time-international normalized ratio (PT-INR) \> 1.0 ULN * Serum bilirubin level \> 1.0 times ULN 8. Individuals on chronic anticoagulation medications. 9. Stool sample positive for GI pathogens potentially causing disease (as assessed by FilmArray GI panel for 22 viral, bacterial, and parasitic organisms that can cause infectious diarrhea \[GI pathogen panel\]). The principal investigator will consult with an infectious disease specialist to review results and decide whether treatment is warranted. 10. Presence of cytomegalovirus (CMV) infection as defined by positive immunohistochemical staining on tissue intestine biopsy. 11. History of low-grade or high-grade colonic mucosal dysplasia. 12. History of bowel surgery other than perianal (e.g., fistulotomy, seton placement, or abscess drainage) within 6 months prior to beginning the CDAI screening diary, Mayo scoring, or Harvey Bradshaw index or drawing screening blood samples. 13. Presence of surgical changes to gut anatomy that preclude administration of clinical activity indices; this includes but is not limited to ileostomy, colostomy, or subtotal colectomy with ileorectal anastomosis. 14. Known or suspected short bowel syndrome. 15. Requirement of parenteral, total parenteral, elemental oral, or nasogastric nutrition. 16. History or current evidence of cancer, other than non-melanomatous cancer of the skin, or participants that have undergone excision of basal cell carcinoma, squamous cell carcinoma of the skin. All patients receiving ustekinumab will be monitored for the appearance of non-melanoma skin cancer. Patients greater than 60 years of age, those with a medical history of prolonged immunosuppressant therapy and those with a history of PUVA treatment will be followed closely. 17. Unwillingness or inability to comply with study requirements. 18. Presence of only small bowel disease that is inaccessible by standard colonoscopy for harvest of research biopsies. Individuals with only upper gastrointestinal disease or only perianal fistulizing disease are also excluded for this reason. 19. Refusal to abstain from using COX-2 inhibitors or non-steroidal anti-inflammatory drugs (NSAIDs) throughout the study agent administration period. 20. Has uncontrolled diabetes 21. Is taking anti-seizure medication, such as valproic acid or its derivative (i.e., Depakote). 22. Presence of any condition that, in the opinion of the principal investigator, contraindicates participation in this study. 23. Has participated in another investigational trial within 8 weeks (or 5 half-lives of any investigational study agent), whichever is greater, prior to the pre-trial (screening) visit. The window will be derived from the last date of treatment on the previous trial.