Stem Cell Transplantation in Crohn's Disease

Summary

Unfortunately, some patients with Crohn's disease (CD) fail to respond to the best clinical treatments and some only experience temporary benefit. For severe Crohn's disease, there is an experimental treatment called "high dose immunoablation" followed by autologous hematopoietic stem cell transplantation (HSCT). This study removes over active lymphocytes (immunoablation) and replaces them using blood stem cells that have been taken from the patient's own body. The aim of the study is to reset or reprogram the patient's immune system to its state prior to diagnosis.

Conditions

• Crohn Disease

Interventions

DRUG

Acetaminophen

Preparative/Conditioning Regime r-ATG premedication according to institutional guidlines

DRUG

Mesna

Stem Cell Mobilization: Infused according to institutional guidelines; Post-PBSC Infusion Conditioning: Mesna provided with Cytoxan according to institutional protocol.

DRUG

Cyclophosphamide

Stem Cell Mobilization: Cyclophosphamide (CY) infused intravenously over 1 hour: 50 mg/kg (25 mg/kg/day on 2 consecutive days)

DRUG

Filgrastim

Stem Cell Mobilization: Filgrastim (G-CSF) 10 mcg/kg SC will start 5 days after the last dose of CY and will end the day before the last leukapheresis; Post-PBSC Infusion Conditioning: Filgrastim administered intravenously 5 mcg/kg IV starting day + 5, continue until ANC of \>1000/μL

PROCEDURE

Apheresis catheter placement

Subjects will require placement of an Apheresis catheter by Intervention Radiologists on the day of collection of stem cells.

PROCEDURE

Leukapheresis

Leukapheresis will be performed on a continuous flow separator machine according to institutional guidelines to target 3-8 x 10\^6 CD34+ cells/kg body weight.

DRUG

Fludarabine

Preparative/Conditioning Regime Fludarabine given as 30 mg/m2 per dose x 4 days, beginning on day -6.

DRUG

Methylprednisolone

Preparative/Conditioning Regime r-ATG pre-medication according to institutional guidelines

DRUG

Diphenhydramine

Preparative/Conditioning Regime r-ATG premedication according to institutional guidelines

DRUG

anti-thymocyte globulin (rabbit)

Preparative/Conditioning Regime r-ATG administered intravenously: 2.5 mg/kg/dose IV over 6 hours on specified days (day -6,-4,-2); ); total 3 doses=7.5 mg/kg.

DRUG

lymphocyte immune globulin

Preparative/Conditioning Regime In patients who develop severe allergic reactions to rATG (Thymoglobulin), it may be substituted by horse ATG (hATG, ATGAM, Pharmacia \& Upjohn, Kalamazoo, MI). The recommended dose of hATG is 25 mg/kg/day for 3 doses.

BIOLOGICAL

Peripheral Blood Stem Cell Infusion

PBSC (peripheral blood stem cell) infusion on day 0 as per institutional guidelines.

DRUG

Cytoxan

Post-PBSC Infusion Conditioning Cytoxan infused intravenously: 50mg/kg/day x 2 days. Infused over 2 hours with adequate hydration or according to institutional guidelines.

Sponsors & Collaborators

• Cedars-Sinai Medical Center

  lead OTHER

Principal Investigators

• David Ziring, MD · Cedars-Sinai Medical Center

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

13 Years

Max Age

28 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-11-15

Primary Completion

2027-09-30

Completion

2027-09-30

FDA Drug

Yes

Countries

• United States

Study Locations