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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for people with severe Crohn's disease. Participants will receive high-dose chemotherapy followed by a transplant of their own specially-selected stem cells (Autologous CD34-selected peripheral blood stem cells transplant). The goal is to determine if this approach is safe and effective in managing the condition. People with challenging cases of Crohn's, such as those who cannot undergo surgery or do not respond well to medication, may be suitable for this trial. As a Phase 1, Phase 2 trial, the study focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that using a patient's own specially selected blood stem cells can help treat severe Crohn's disease, especially for those who haven't succeeded with other treatments. Studies indicate that this approach is generally well-tolerated, despite the need for strong chemotherapy before the stem cell infusion.

Safety data suggests that while some patients may experience side effects like infections or low blood counts, others handle the treatment without major problems. These stem cell transplants use the patient's own cells, reducing the risk of rejection. Although the treatment is still under study, using the patient's own cells adds an extra layer of safety.

As the trial is in its early stages, researchers are closely monitoring the treatment's safety. Prospective participants should talk to the study team for detailed information about what to expect. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Crohn's disease?

Unlike the standard treatments for Crohn's disease, which typically involve anti-inflammatory drugs, corticosteroids, or biologics that suppress the immune system, the autologous CD34-selected peripheral blood stem cell transplant offers a novel approach. This treatment is unique because it uses the patient’s own stem cells to reboot the immune system after high-dose immunotherapy. Researchers are excited about this method as it has the potential to induce long-term remission by targeting the underlying immune dysfunction in Crohn's disease, rather than just managing symptoms. This innovative approach could offer new hope for patients who don't respond well to existing therapies.

What evidence suggests that this treatment might be an effective treatment for Crohn's disease?

Research has shown that using a person's own stem cells for treatment, known as autologous hematopoietic stem cell transplantation (AHSCT), is effective for severe Crohn's disease, particularly when other treatments have failed. In this trial, participants will receive high-dose immunotherapy followed by an infusion of autologous CD34-selected peripheral blood stem cells. Studies have found that patients who received AHSCT experienced significant symptom improvement. For some, the disease remained in remission, meaning it was inactive, for a long time after treatment. Early findings suggest this treatment helps reset the immune system, potentially reducing gut inflammation. While more research is needed, these early results offer promise for those with difficult-to-treat Crohn's disease. ^{1 2 3 4 6}

Who Is on the Research Team?

Paul Szabolcs, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

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

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

I have responded to treatment without needing steroids continuously.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT00692939

Autologous Stem Cell Transplantation for Crohn's Disease The objective of this study is to evaluate the safety and effectiveness of administering high-dose chemotherapy followed by infusion of autologous CD34-selected ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12147729/

Hematopoietic stem cell transplantation in Crohn's disease In this review, we examine the role of SCT in refractory CD focusing on clinical outcomes, safety considerations, and future directions.

3. withpower.com withpower.com/trial/phase-2-crohn-disease-5-2012-7e2ac

Stem Cell 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 ...

4. clinconnect.io clinconnect.io/trials/NCT00692939

Autologous Stem Cell Transplantation for Crohn's Disease The objective of this study is to evaluate the safety and effectiveness of administering high-dose chemotherapy followed by infusion of autologous ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6544952/

Autologous stem cell transplantation in refractory Crohn's ... Case reports suggest potential benefit after haematopoietic stem cell transplant (HSCT) for patients with refractory CD. The ASTIC trial asked whether HSCT ...

6. mdpi.com mdpi.com/2073-4409/11/21/3463

Hematopoietic Stem Cell Transplantation in Refractory ... This review aims to describe the current role of HSCT in CD and discusses the procedure, the correct patient selection, the clinical efficacy