Autologous Stem Cell Transplant for Crohn's Disease

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

Interventions

PROCEDURE

Autologous stem cell transplant

Hematopoietic stem cell transplantation

DRUG

Cyclophosphamide

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

DRUG

Cyclophosphamide

Day -6 to -3: Cyclophosphamide 50 mg/kg/day (200 mg/kg total dose)

DRUG

Thymoglobulin

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

DRUG

Methylprednisolone

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

DRUG

Vedolizumab

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)

Sponsors & Collaborators

• Aaron Etra

  lead OTHER

Principal Investigators

• Aaron Etra, MD · Icahn School of Medicine at Mount Sinai

• Louis Cohen, MD · Icahn School of Medicine at Mount Sinai

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-02-22

Primary Completion

2028-10-31

Completion

2028-10-31

FDA Drug

Yes

Countries

• United States

Study Locations