Autologous Stem Cell Transplant for Crohn's Disease

NCT03219359 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: GCO 17-0378
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Crohn's Disease (CD) is an inflammatory bowel disease. It can lead to significant complications and discomfort in the stomach and intestines. Crohn's disease is a debilitating, incurable disease of immune cells; it affects almost 1 million people in the United States. CD is characterized by inflammation of the stomach and intestine as well as organs outside of the intestines such as the skin, eyes, and joints. Current therapies to treat CD aim to suppress the patient's immune cells but these therapies become ineffective for the majority of patients and lead to complications including the requirement for surgical bowel resection, impaired quality of life, and lifelong disability. Hematopoietic stem cell transplantation (HCT) is a procedure used to treat a number of medical conditions including Crohn's disease. To improve success of HCT in CD doctors considered combining transplant with other drugs to improve the chances of achieving remission and also maintaining the remission. The Investigators' plan in this study is to incorporate the drug Vedolizumab after transplant to test if this drug will improve remission and make patients healthier. Patients may qualify to take part in this research study because Crohn's disease is active, because surgery is not a treatment option and because there is evidence that the disease has failed to respond to treatments for Crohn's disease including the following:

• corticosteroids
• azathioprine, 6-mercaptopurine, methotrexate
• Anti-TNFα (infliximab, adalimumab, certolizumab, golimumab)
• Anti-integrin agents (natalizumab, Vedolizumab) If patients meet entry criteria will undergo a baseline endoscopy, colonoscopy and MR or CT enterography. If documentation of active mucosal disease patients will then be tapered off of current medications and undergo stem cell mobilization. Mobilization will involve low dose chemotherapy, growth factors and require 1-2 week hospitalization. Patients will then undergo stem cell transplant which will involve high dose chemotherapy and require a 2-4 week hospitalization. After restoration of the immune system patients will be placed on vedolizumab per standard dosing (0,2,6 then 8 every weeks) for a total of 8 doses. Patients will have monthly study visits and a repeat colonoscopy and MR/CT scan at 6 months.

Conditions

Crohn Disease

Keywords

IBD; Inflammatory Bowel Diseases; Gastroenteritis; Crohn's disease; Colitis; Vedolizumab

Outcome Measures

Primary Outcomes (1)

• Change in Crohn's Disease Activity Index (CDAI)

  The proportion of patients in clinical remission, defined as a CDAI \< 150, one year after autologous HCT from 45% to 65% as compared to baseline.

  baseline and 1 year post transplant

Secondary Outcomes (1)

• Change in endoscopic activity indices

  baseline and 1 year post transplant

Other Outcomes (2)

• Change in burden of intestinal disease

  baseline and 1 year post transplant

• Change in Inflammatory Bowel Disease Questionnaire (IBDQ)

  baseline and 1 year post transplant

Study Arms (1)

Experimental

EXPERIMENTAL

Hematopoietic Stem Cell Transplant followed by maintenance Vedolizumab

Procedure: Autologous stem cell transplant; Drug: Cyclophosphamide; Drug: Thymoglobulin; Drug: Methylprednisolone; Drug: Vedolizumab

Interventions

Autologous stem cell transplant PROCEDURE

Hematopoietic stem cell transplantation

Also known as: Bone Marrow Transplant

Experimental

Cyclophosphamide DRUG

Days 1 and 2: Cyclophosphamide 2gm/m2/day x 2 days (total dose 4gm/m2) Day 3 until leukapheresis: G-CSF 10μg/kg/day to CD34+ \>20x104/ml then leukapheresis daily to collection goal

Experimental

Thymoglobulin DRUG

Day -3 to -1: 2.5 mg/kg/day (7.5 mg/kg total dose)

Also known as: ATG

Experimental

Methylprednisolone DRUG

Day -3 to -1: 1 gram prior to each ATG dose

Experimental

Vedolizumab DRUG

Starting first day after discharge from transplant admission, then 2 weeks after 1st infusion, 4 weeks after 2nd infusion, followed by every 8 weeks for 52 weeks (8 doses)

Experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of Crohn's disease by standard criteria
• Active disease based on clinical symptoms, defined as CDAI \>250. In patients with an ostomy, the number of liquid stools score in the CDAI will be replaced by the number of times that the ostomy bag is emptied daily.
• Active disease based on endoscopic evaluation, defined as SES-CD score \> 3 in at least one bowel segment
• Failure to respond to (or intolerant/adverse reaction to or declines) a member of each of the class of drugs listed below:
• corticosteroids
• azathioprine,
• mercaptopurine, methotrexate
• Anti-TNFα (infliximab, adalimumab, certolizumab, golimumab)
• Anti-integrin agents (natalizumab, vedolizumab)
• Ustekinumab
• Failure to respond refers to ongoing objective inflammation with symptoms and, as is traditional, is defined by the gastroenterologist evaluating the patient.
• No surgical therapeutic option secondary to risk of short bowel syndrome or patient refusal

You may not qualify if:

• History of significant toxicity to any medications used in trial (cyclophosphamide, thymoglobulin, vedolizumab)
• Pregnant or breastfeeding
• Age \<18
• Karnofsky Performance Score \<60
• Patients who have an uncontrolled infection (presumed or documented) despite appropriate therapy for at least one month
• Patients with symptomatic coronary artery disease or uncontrolled congestive heart failure.
• HIV infected
• Ejection fraction \<30% or requiring supplemental continuous oxygen.
• DLCO \<35% or requiring supplementary oxygen.
• Patients for whom an insufficient number of stem cells (\<2 X 10\^6/kg) have been collected.

Sponsors & Collaborators

• Aaron Etra: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

MeSH Terms

Conditions

Crohn Disease; Inflammatory Bowel Diseases; Gastroenteritis; Colitis

Interventions

Bone Marrow Transplantation; Cyclophosphamide; thymoglobulin; Methylprednisolone; vedolizumab

Condition Hierarchy (Ancestors)

Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colonic Diseases

Intervention Hierarchy (Ancestors)

Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Aaron Etra, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Louis Cohen, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Louis Cohen, MD

CONTACT

(212) 241-8100; louis.cohen@mssm.edu

Aaron Etra, MD

CONTACT

aaron.etra@mountsinai.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: July 13, 2017
• First Posted: July 17, 2017
• Study Start: February 22, 2018
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2028
• Last Updated: November 5, 2025

Record last verified: 2025-10

Locations

US (1)