Stem Cell Transplant for Crohn's Disease

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Stanford University

Disqualifiers: Ulcerative colitis, Severe cardiovascular, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a special type of stem cell transplant, Allogeneic HSCT, can safely replace the immune system in people with Crohn's disease unresponsive to regular treatments. The main aim is to determine if this approach benefits individuals with early-onset Crohn’s that doesn't improve with typical medications. Those with a genetic form of Crohn's or symptoms unmanageable by drugs may be suitable for the study. 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.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Previous studies have shown some promise in using transplants with donated blood stem cells to treat Crohn's disease. In one study, 68% of patients experienced significant improvement in their symptoms, known as clinical remission. However, safety remains a critical concern. Notably, all patients survived three years after the procedure, which is reassuring. Still, risks exist. Toxicity, or harmful effects on the body, has been a barrier to widespread use of this treatment. While it can be effective for some, it might not be safe for everyone. Ongoing trials, such as the one you might join, aim to gather more information on these safety concerns. ^{1 2 3 4 5}

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

Researchers are excited about using allogeneic hematopoietic stem cell transplant (HSCT) for Crohn's disease because it offers a unique approach compared to standard treatments like immunosuppressants and biologics. Unlike these typical treatments, which primarily aim to reduce inflammation, HSCT involves the transplantation of stem cells to potentially reset the immune system. This method targets the underlying immune dysregulation in Crohn's disease, offering the possibility of long-term remission. By using αβ-depleted stem cells, this treatment also aims to minimize the risk of graft-versus-host disease, which is a common concern with transplants.

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

Research has shown that allogeneic hematopoietic stem cell transplant (HSCT) might be a promising treatment for Crohn's disease, especially when other treatments fail. In this trial, participants will undergo an αβ-depleted HSCT following a conditioning regimen. One study found that patients went into remission without needing medication, meaning they no longer required drugs to control their symptoms. Another study found that many patients stayed in remission for several years after the transplant. Specifically, 91% were in remission after the first year, and about 39% remained symptom-free after four years. These encouraging results suggest that HSCT could be an effective option for Crohn's disease patients who haven't responded to other treatments. ^{1 2 3 4 6}

Who Is on the Research Team?

Jessie Alexander, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for Crohn's disease patients aged 2-30 with specific genetic causes or severe cases not responding to treatment. Participants must have a minimum Lansky/Karnofsky score of 50, agree to birth control if applicable, and have a donor match at certain genetic points. It excludes those with treatable extraintestinal symptoms, certain mutations, active HLH, organ dysfunction, HIV/HBV/HCV infections, prior radiation therapy or HSCT, recent cancer (with exceptions), pregnancy/breastfeeding, or inability to consent.

Inclusion Criteria

I am between 2 and 30 years old.

My donor and I are a genetic match at specific points.

Ability to provide informed consent or have a legally authorized representative available

Exclusion Criteria

HIV-infected patients or patients with chronic HBV or HCV infection

I have ulcerative colitis.

I have been diagnosed with active HLH.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Regimen

Participants receive a conditioning regimen prior to hematopoietic stem cell transplantation (HSCT)

1-2 weeks

Hematopoietic Stem Cell Transplantation (HSCT)

Participants undergo TCRαβ+ T-cell/CD19+ B-cell depleted HSCT to induce immune tolerance

Immediate post-conditioning

Post-Transplant Monitoring

Participants are monitored for myeloid engraftment and acute graft vs host disease (GVHD)

6 months

Regular visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including remission of Crohn disease and immune function

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Allogeneic HSCT

Trial Overview The study tests whether alpha beta T-cell depleted HSCT from partially matched donors can replace the immune system in early-onset Crohn's disease. The process involves using drugs like Palifermin and Clofarabine along with TCRα/β+ T-cell/CD19+ B-cell depletion kits and other treatments such as ATG and Rituximab.

How Is the Trial Designed?

Group I: Cohort 2a Experimental Treatment 8 Interventions

If the intervention is determined to be safe and non-futile, the study will continue to enroll 10 more patients under Phase 2a following the same treatment as Phase 1b.

Group II: Cohort 1b: Safety Lead-In Experimental Treatment 8 Interventions

An initial cohort of 4 patients will be enrolled as part of the initial Phase 1b safety run-in evaluation. Patients will undergo an αβdepleted hematopoietic stem cell transplant (HSCT) after receiving a conditioning regimen.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1542356525004045

Outcomes of Allogeneic Hematopoietic Stem Cell ... HSCT resulted in IBD medication-free remission and reduction in disease-associated complications. This highlights the strength of genetic evaluation in ...

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

Hematopoietic stem cell transplantation in Crohn's disease All patients achieved clinical remission with relapse-free survival of 91% at 1 year, 63% at 2 years, 57% at 3 years, 39% at 4 years, and 19% at ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01570348

NCT01570348 | Crohn's Allogeneic Transplant Study This phase II trial studies how well giving a donor bone marrow transplant (BMT) works in treating patients with refractory Crohn's Disease.

4. thelancet.com thelancet.com/journals/langas/article/PIIS2468-1253(23)00460-0/fulltext

Safety and efficacy of autologous haematopoietic stem-cell ... Despite the potential efficacy of HSCT, toxicity remains a substantial barrier to its use in patients with Crohn's disease. An analysis that ...

5. ajmc.com ajmc.com/view/stem-cell-transplant-offers-hope-for-children-with-severe-monogenic-ibd

Stem Cell Transplant Offers Hope for Children With Severe ... Allogeneic HSCT achieved 92% sustained, medication-free remission and 100% survival in children with monogenic IBD, highlighting its potential ...

6. cghjournal.org cghjournal.org/article/S1542-3565(25)00404-5/abstract

Outcomes of Allogeneic Hematopoietic Stem Cell ... There was 100% survival at a median follow-up of 3 years. Prior to transplant, 76% of patients received immunosuppression, and 20% underwent IBD ...