Stem Cell Transplant for Crohn's Disease

Recruiting at 1 trial location

Overseen By Shawna H McIntyre, RN

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Paul Szabolcs

Must be taking: 6-MP, 5-ASA, Metronidazole

Must not be taking: Anti-TNF, Anti-integrin, Anti-IL12/23

Disqualifiers: Toxic megacolon, Intestinal perforation, Pregnancy, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the trial involves high-dose chemotherapy, it's possible that some medications might need to be adjusted or stopped. Please consult with the trial coordinators for specific guidance.

What data supports the effectiveness of the treatment Autologous CD34-selected peripheral blood stem cells transplant for Crohn's Disease?

Research shows that autologous haematopoietic stem cell transplantation (AHSCT) has been effective in treating severe, treatment-resistant Crohn's disease, with studies indicating good safety and promising results. The ASTIC trial and other studies have suggested benefits for patients undergoing this treatment. ^{1 2 3 4 5}

Is autologous stem cell transplantation safe for humans?

Autologous stem cell transplantation for Crohn's disease has been studied and generally shows good safety, although it can be associated with some risks like mortality and adverse events. The balance between risks and benefits is important, and safety data from various studies suggest it is generally safe for humans. ^{1 2 3 5 6}

How is the Autologous CD34-selected PBSC transplant treatment different from other treatments for Crohn's disease?

The Autologous CD34-selected PBSC transplant is unique because it involves using a patient's own stem cells to reset the immune system, which is different from standard drug treatments that typically aim to reduce inflammation or suppress the immune response. This approach is considered for severe cases of Crohn's disease that do not respond to other treatments. ^{1 2 3 5 6}

What is the purpose of this trial?

The objective of this study is to evaluate the safety and effectiveness of administering high-dose chemotherapy followed by infusion of autologous CD34-selected peripheral blood stem cells (PBSC) in pediatric and adult patients with severe Crohn's disease.

Research Team

Paul Szabolcs, MD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for pediatric and adult patients aged 10-60 with severe Crohn's disease who haven't responded to aggressive medical treatments or can't have surgery without risking short bowel syndrome. Participants must understand the consent process, not be pregnant, agree to use birth control post-transplant, and meet specific health criteria like adequate blood counts and organ function.

Inclusion Criteria

I have severe Crohn's disease not responding to treatment and might need a stem cell transplant.

Subject and/or guardian must be able to understand and provide informed consent

I am a female over 10 or have started my periods, not pregnant, and agree to use birth control.

Exclusion Criteria

I have responded to treatment without needing steroids continuously.

Past or current medical problems or findings that may pose additional risks, interfere with study requirements, or impact data quality

I have not had a severely swollen colon or a tear in my intestine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

High-dose Chemotherapy

Participants receive high-dose chemotherapy as part of the treatment protocol

2-3 weeks

Stem Cell Infusion

Infusion of autologous CD34-selected peripheral blood stem cells (PBSC)

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Autologous CD34-selected peripheral blood stem cells transplant

Trial Overview The study tests high-dose chemotherapy followed by an infusion of the patient's own CD34-selected peripheral blood stem cells. The goal is to assess if this approach is safe and effective in treating severe Crohn's disease that hasn’t improved with standard therapies.

Participant Groups

Group I: 1 Experimental Treatment 9 Interventions

High-dose immunotherapy followed by infusion of autologous CD34-selected peripheral blood stem cells (PBSC)

Autologous CD34-selected peripheral blood stem cells transplant is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Autologous CD34-selected PBSC transplant for:

• Multiple sclerosis
• Systemic lupus erythematosus
• Systemic sclerosis
• Rheumatoid arthritis
• Juvenile idiopathic arthritis

Approved in United States as Autologous CD34-selected PBSC transplant for:

• Multiple sclerosis
• Systemic lupus erythematosus
• Crohn's disease

Approved in Canada as Autologous CD34-selected PBSC transplant for:

• Multiple sclerosis
• Systemic lupus erythematosus

Who Is Running the Clinical Trial?

Paul Szabolcs

Lead Sponsor

Trials

8

Recruited

230+

Findings from Research

In a study of 82 patients with severe, treatment-refractory Crohn's disease who underwent autologous haematopoietic stem cell transplantation (AHSCT), 68% experienced complete remission or significant symptom improvement at a median follow-up of 41 months, indicating AHSCT's potential efficacy.

AHSCT was found to be relatively safe, with only one patient dying from an infectious complication, suggesting that while there are risks, the treatment can effectively manage Crohn's disease that has not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous Haematopoietic Stem Cell Transplantation for Crohn's Disease: A Retrospective Survey of Long-term Outcomes From the European Society for Blood and Marrow Transplantation. Brierley, CK., Castilla-Llorente, C., Labopin, M., et al.[2022]

In a study involving 4 patients with moderate-severe refractory Crohn's disease, autologous hematopoietic stem cell transplantation (HSCT) using unselected peripheral blood stem cells (PBSCs) resulted in clinical remission for all patients by the third month, with significant improvement in disease activity scores.

The treatment was found to be safe, with no deaths or life-threatening infections reported, and 3 out of 4 patients maintained remission for over 16 months, indicating the potential long-term benefits of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous haematopoietic stem cell transplantation without CD34+ cell selection in refractory Crohn's disease. Cassinotti, A., Annaloro, C., Ardizzone, S., et al.[2022]

In a retrospective study of 7 patients with refractory Crohn's disease who underwent autologous haematopoietic stem cell transplantation (AHSCT), 71% achieved clinical remission after a mean follow-up of 48 months, indicating AHSCT's potential as an effective treatment option.

While symptoms recurred in 71% of patients, AHSCT allowed for some patients to respond to treatments they previously did not respond to, suggesting it can make the disease more manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous haematopoietic stem cell transplantation in refractory Crohn's disease: Experience in our centre. Hernanz, N., Sierra, M., Volpato, N., et al.[2019]

Autologous haematopoietic stem cell transplantation (HSCT) effectively induces and maintains clinical and endoscopic remission in patients with moderate-severe refractory Crohn's disease, as shown through immunological analyses over a 12-month follow-up period.

The treatment leads to significant immunomodulation, characterized by an increase in regulatory T cells (T-regs) and a decrease in pro-inflammatory markers like TNF-alpha and IL-12, which correlates with improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulatory effects of unselected haematopoietic stem cells autotransplantation in refractory Crohn's disease. Clerici, M., Cassinotti, A., Onida, F., et al.[2017]

The ASTIC trial suggests that immunoablation followed by stem cell transplantation can significantly improve symptoms in some patients with Crohn's disease, as indicated by a notable reduction in the Crohn's Disease Activity Index (CDAI) and C-reactive protein levels after treatment.

However, the treatment carries significant risks, including serious adverse events and infections, which may limit its suitability to only a select group of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem cells as treatment in inflammatory bowel disease. Hawkey, CJ.[2013]

Autologous hematopoietic stem cell transplantation (HSCT) shows a high efficacy rate for refractory Crohn's disease, achieving clinical remission in approximately 79.4% of patients and endoscopic remission in about 81.9%, based on a meta-analysis of multiple studies.

Despite its effectiveness, autologous HSCT carries a significant risk of complications, including a 6.4% rate of transplant-related mortality and a high incidence of febrile neutropenia (83.2%), indicating that this treatment should be approached with caution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of autologous hematopoietic stem cell therapy for refractory Crohn's disease: A systematic review and meta-analysis. Qiu, X., Feng, JR., Chen, LP., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Autologous Haematopoietic Stem Cell Transplantation for Crohn's Disease: A Retrospective Survey of Long-term Outcomes From the European Society for Blood and Marrow Transplantation. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Autologous haematopoietic stem cell transplantation without CD34+ cell selection in refractory Crohn's disease. [2022]

3. Spain pubmed.ncbi.nlm.nih.gov

Autologous haematopoietic stem cell transplantation in refractory Crohn's disease: Experience in our centre. [2019]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Immunomodulatory effects of unselected haematopoietic stem cells autotransplantation in refractory Crohn's disease. [2017]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Stem cells as treatment in inflammatory bowel disease. [2013]

6. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of autologous hematopoietic stem cell therapy for refractory Crohn's disease: A systematic review and meta-analysis. [2021]