Ignite Creation Date:
2025-12-25 @ 12:05 AM
Ignite Modification Date:
2025-12-25 @ 10:03 PM
Study NCT ID:
NCT04224558
Status:
RECRUITING
Last Update Posted:
2025-02-24
First Post:
2018-04-04
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Stem Cell Transplantation in Crohn's Disease
Sponsor:
Cedars-Sinai Medical Center
Organization:
Study Overview
Official Title:
Autologous Hematopoietic Stem Cell Transplantation for Refractory Crohn's Disease
Status:
RECRUITING
Status Verified Date:
2025-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
Detailed Description:
The treatment of Crohn's disease has proven to be quite efficacious in the majority of patients with the timely use of combination therapies for remission induction (corticosteroids and/or biologics) and maintenance of disease control (immunosuppressives and/or biologics). However, a proportion of patients fail to achieve complete and long term disease control and often require multiple intestinal surgeries with a risk of developing short bowel syndrome. Lymphoablation followed by hematopoietic stem cell transplantation to rescue the immune system has been proposed as an alternative strategy to induce long term disease control in this high-risk population. It has been demonstrated that despite the potential toxicity and morbidity associated with the procedure, the benefit-risk ratio is favorable. Hence, the investigators propose to offer HSCT to selected CD patients and to study mechanisms of reducing T cell autoreactivity which will hopefully lead to more focused therapeutic approaches in the future.
This is an open-label, non-randomized, non-blinded, prospective study in therapeutic refractory Crohn's patients, failing conventional therapy.
The primary objective is to evaluate the safety and potential clinical benefit of lymphoablation followed by autologous HSCT rescue in therapy refractory CD. Death (transplant-related mortality, TRM) and severe toxicity (≥ grade 3 toxicity; NCI Toxicity Criteria version 4.0) within the first 6 months after HSCT will be monitored to meet this end-point.
SECONDARY OBJECTIVES
1. To evaluate the incidence of HSCT related complications, i.e. viral reactivations (CMV, Adenovirus, EBV, BK virus) or fungal infections.
2. To evaluate the impact of HSCT on quality of life and school productivity.
3. To elucidate the underlying mechanism involved in the observed benefit of HSCT on CD.
First, the safety will be evaluated by the amount of related adverse events. All adverse events will be recorded in a standardized way and their relationship to the study protocol will be assessed at various short and long term time points.
Second, to determine clinical benefit, the percentage of patients in sustained disease remission at 0, 2, 4, 6, 12 and 24 months post HSCT will be determined. Sustained disease remission is defined as a Crohn's Disease Activity Index (CDAI) \< 150 without the use of corticosteroids. In addition, mucosal healing will be assessed during ileocolonoscopy at 6 and 12 months following HSCT using the CD endoscopic index (SES).
SECONDARY ENDPOINTS
\- Change in Crohn's disease endoscopic index after 6 and 12 months.
This is an open-label, non-randomized, non-blinded, prospective study in therapeutic refractory Crohn's patients, failing conventional therapy.
The primary objective is to evaluate the safety and potential clinical benefit of lymphoablation followed by autologous HSCT rescue in therapy refractory CD. Death (transplant-related mortality, TRM) and severe toxicity (≥ grade 3 toxicity; NCI Toxicity Criteria version 4.0) within the first 6 months after HSCT will be monitored to meet this end-point.
SECONDARY OBJECTIVES
1. To evaluate the incidence of HSCT related complications, i.e. viral reactivations (CMV, Adenovirus, EBV, BK virus) or fungal infections.
2. To evaluate the impact of HSCT on quality of life and school productivity.
3. To elucidate the underlying mechanism involved in the observed benefit of HSCT on CD.
First, the safety will be evaluated by the amount of related adverse events. All adverse events will be recorded in a standardized way and their relationship to the study protocol will be assessed at various short and long term time points.
Second, to determine clinical benefit, the percentage of patients in sustained disease remission at 0, 2, 4, 6, 12 and 24 months post HSCT will be determined. Sustained disease remission is defined as a Crohn's Disease Activity Index (CDAI) \< 150 without the use of corticosteroids. In addition, mucosal healing will be assessed during ileocolonoscopy at 6 and 12 months following HSCT using the CD endoscopic index (SES).
SECONDARY ENDPOINTS
\- Change in Crohn's disease endoscopic index after 6 and 12 months.
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: