Stem Cell Transplant for Crohn's Disease

Overseen By Yvette Gonzales, MBA

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Cedars-Sinai Medical Center

Must be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Pregnancy, Severe renal, Cardiac, Pulmonary, Psychiatric disorders, others

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

Compensation: Varies

Number of Visits: Unknown

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with severe Crohn's disease who haven't found relief with current medications. Researchers aim to determine if high dose immunoablation (removing overactive immune cells) followed by a stem cell transplant can reset the immune system to its pre-disease state. Participants will receive an infusion of their own stem cells (peripheral blood stem cell infusion) after specific preparation steps. The trial seeks individuals with Crohn's disease that hasn't improved with other treatments and who aren't suitable for surgery. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications, but it mentions that participants should have an unsatisfactory response to certain immunosuppressive drugs. It's best to discuss your current medications with the trial team.

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

Research has shown that using peripheral blood stem cells to treat Crohn's disease appears promising in early studies. Many patients who received this treatment experienced significant symptom improvement, achieving clinical remission. In one study, 91% of patients were symptom-free after one year. However, this number decreased over time, with 63% still in remission after two years and 57% after three years.

Regarding safety, early findings suggest the treatment is generally well-tolerated, though some risks exist. A combined analysis of several studies found that 25% of patients achieved clinical remission after stem cell therapy. This indicates that while the treatment can be effective, it doesn't work for everyone. It's important to weigh both the potential benefits and risks before deciding to join a clinical trial. ^{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 often rely on anti-inflammatory drugs and immunosuppressants, this new approach utilizes peripheral blood stem cell infusion. This method is unique because it involves mobilizing and harvesting stem cells from the patient’s blood, conditioning them, and then infusing them back into the body. Researchers are excited because this could potentially reset the immune system, offering a long-term, possibly more effective option for managing Crohn's Disease compared to existing therapies. Additionally, this treatment might reduce reliance on long-term medication, which can have significant side effects.

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

Research has shown promising results for using stem cell transplants to treat severe Crohn's disease. In one study, all patients experienced significant improvement in their symptoms, achieving clinical remission. After one year, 91% of these patients remained well without any return of symptoms. Another study found that about 46% of patients reached remission after receiving stem cell therapy. This trial includes a treatment arm where participants undergo stem cell mobilization, leukapheresis, a preparative regimen, and peripheral blood stem cell infusion, followed by post-transplant conditioning. This treatment resets the immune system to better manage the disease. While the results are hopeful, relapses can still occur, so regular check-ups remain important. ^{1 2 3 4 5}

Who Is on the Research Team?

David Ziring, MD

Principal Investigator

Cedars-Sinai Medical Center

Are You a Good Fit for This Trial?

This trial is for young people aged 13-28 with severe Crohn's Disease, who haven't responded well to at least three immunosuppressive drugs and steroids. They must have active disease, be informed about the risks, and not suitable for surgery or at risk of short bowel syndrome. Pregnant individuals or those unwilling to use contraception are excluded.

Inclusion Criteria

Prepared to undergo additional study procedures as per trial schedule

Accepted by a majority of the members of the combined IBD Center as an appropriate candidate (see Selection description below)

You have tried three different medications to control your condition, along with corticosteroids, but they haven't worked well enough.

Exclusion Criteria

Pregnancy or unwillingness to use adequate contraception during the study, in women of childbearing age

Males who are not willing to use birth control methods when needed.

Concomitant severe disease: renal: creatinine clearance < 30 mL/min (measured or estimated), cardiac: clinical evidence of refractory congestive heart failure; left ventricular ejection fraction < 40% by cardiac echo; chronic atrial fibrillation necessitating oral anticoagulation; uncontrolled ventricular arrhythmia; pericardial effusion with hemodynamic consequences as evaluated by an experienced echo cardiographer, pulmonary: diffusion capacity <40%, psychiatric disorders including active drug or alcohol abuse, concurrent or recent history of malignant disease (excluding non-melanoma skin cancer), uncontrolled hypertension, defined as resting systolic blood pressure ≥ 140 and/or resting diastolic pressure ≥ 90 despite at least 2 anti-hypertensive agents, any infection with HIV, HTLV-1 or 2, hepatitis viruses, or any other infection the investigators consider a contraindication to participation, other chronic disease causing significant organ failure

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Mobilization and Conditioning

Participants undergo stem cell mobilization and conditioning prior to transplantation

4-6 weeks

Multiple visits for mobilization and conditioning procedures

Stem Cell Transplantation

Participants receive autologous hematopoietic stem cell transplantation

1 week

Inpatient stay for transplantation

Post-Transplant Conditioning

Participants receive post-transplant conditioning to support engraftment

2-4 weeks

Inpatient and outpatient visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Regular visits at 0, 2, 4, 6, 12, and 24 months post HSCT

What Are the Treatments Tested in This Trial?

Interventions

• Peripheral Blood Stem Cell Infusion

Trial Overview

The study tests 'high dose immunoablation' followed by autologous hematopoietic stem cell transplantation (HSCT) in patients with Crohn's Disease. It aims to reset the immune system by removing overactive lymphocytes and replacing them with the patient's own blood stem cells.

How Is the Trial Designed?

Group I: HSCT after mobilization and conditioning Experimental Treatment 13 Interventions

Mobilization and leukopheresis allow for stem cell harvest. Then conditioning is provided prior to stem cell transplantation, followed by post-transplant conditioning. Interventions include: 1. Stem cell mobilization 2. Leukopheresis 3. Preparative regimen 4. Peripheral blood stem cell infusion 5. Post-PBSC infusion conditioning

Who Is Running the Clinical Trial?

Cedars-Sinai Medical Center

Lead Sponsor

Trials

523

Recruited

165,000+

Published Research Related to This Trial

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]

A study involving 33 children with cancer assessed the safety of infusing cryopreserved peripheral blood stem cells (PBSC), revealing that vomiting was the only significant toxicity related to the DMSO used in the grafts.

While most children tolerated the infusions well, eight experienced transient shock, highlighting a potential risk associated with thawed blood cell grafts that requires careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical toxicity at the infusion of cryopreserved and thawed peripheral blood stem cell grafts in children]. Okamoto, Y., Takaue, Y., Yasutomo, K., et al.[2007]

In a study of 17 patients undergoing high-dose chemotherapy for various cancers, the use of peripheral blood stem cells led to a significantly faster recovery of blood cell counts compared to traditional bone marrow infusion, indicating enhanced efficacy of this treatment approach.

The accelerated recovery resulted in fewer transfusions needed for platelets and red blood cells, reduced fever periods, and earlier hospital discharge, suggesting that peripheral stem cell transplantation could be a safer and more effective alternative to autologous bone marrow transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Favorable effect of hematopoietic stem cells isolated from blood on hematologic recovery following high-dosage chemotherapy]. Richel, DJ., Baars, JW., Wijngaarden, MJ., et al.[2006]

In a study of 213 pediatric patients undergoing hematopoietic stem cell transplantation, serious adverse reactions (ARs) during cellular therapy product infusions occurred in 25% and 11% of cases, with no severe grade 4 or 5 reactions reported.

The source of stem cells significantly influenced the risk of serious ARs, with cord blood being associated with a higher risk, while manipulated cellular therapy products were found to be protective, suggesting they can help reduce adverse reactions during infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse reactions during stem cell infusion in children treated with autologous and allogeneic stem cell transplantation. Truong, TH., Moorjani, R., Dewey, D., et al.[2018]

A policy change in December 2007 that limited the total nucleated cell dose to less than 1.63 × 10(9) TNC/kg/day during autologous stem cell transplants significantly reduced severe infusion-related adverse events from 4% to 0.6%.

The change also led to an increase in the percentage of patients requiring multiple day infusions from 6% to 24%, but this did not affect the time to engraftment or the overall costs of the transplantation procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limiting the daily total nucleated cell dose of cryopreserved peripheral blood stem cell products for autologous transplantation improves infusion-related safety with no adverse impact on hematopoietic engraftment. Khera, N., Jinneman, J., Storer, BE., et al.[2021]

In a study of 1680 related donors of hematopoietic cell transplants, only 12 severe adverse events (SAEs) were reported, indicating a low incidence rate of 0.71%, with no fatalities among donors.

Most SAEs occurred in donors who were either overweight or obese, and some had pre-existing medical conditions that could have made them ineligible for donation, highlighting the importance of careful donor screening and counseling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious Adverse Events in Related Donors: A Report from the Related Donor Safe Study. Seftel, MD., Chitphakdithai, P., Miller, JP., et al.[2023]

The use of peripheral blood stem cells (PBSC) for allogeneic transplantation has significantly increased over the past 9 years, with over 50% of sibling and 25% of unrelated donor transplants utilizing PBSC, primarily due to faster recovery of blood cell production.

Randomized trials indicate that PBSC transplantation offers a survival advantage for patients with advanced leukemia, mainly by reducing transplant-related mortality, although it is associated with a higher risk of chronic graft-versus-host disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic transplantation using peripheral blood stem cells. Russell, NH., Byrne, JL.[2005]

Peripheral blood stem cell transplantation (PBSCT) offers significant advantages over traditional bone marrow transplants, including faster recovery of blood cells, reduced complications, and cost-effectiveness, making it a preferred option for patients with blood cancers.

Recent advancements in stem cell research and techniques, such as cytokine manipulation and gene therapy, are expanding the potential applications of PBSCT beyond cancer treatment to include certain nonmalignant diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peripheral Blood Stem Cells: Transplantation and Beyond. Lie, AK., To, LB.[2019]

Peripheral stem cells, particularly mononuclear cells, are gaining attention in transfusion therapy due to their ability to support hematopoietic reconstitution and treat various disorders.

Despite their low concentration in blood making collection challenging, the routine harvesting of these cells reflects their growing importance in medical treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Collection and use of circulating hematopoietic progenitor cells. Lee, JH., Klein, HG.[2004]

Peripheral blood stem cell transplantation can lead to severe complications, such as graft versus host disease (GVH) and subsequent organ failure, particularly in immunocompromised patients.

Adenoviral infections pose a significant risk for these patients, potentially leading to fatal outcomes, highlighting the need for improved diagnostics and early treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Multiple organ failure and disseminated adenoviral infection]. Bretonnière, C., Touzeau, C., Guillaume, T., et al.[2010]

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]

Haematopoietic stem cell transplantation shows promise for treating Crohn's disease, with case reports indicating significant improvements and potential cures in some patients.

A clinical trial is underway to evaluate the effectiveness of stem cell transplantation specifically for Crohn's disease, highlighting the need to understand both immune and non-immune factors in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem cell transplantation for Crohn's disease. Hawkey, CJ.[2008]

The review of 18 studies on hematopoietic stem cell transplantation found that mild and moderate adverse reactions were most common, with nausea and vomiting being the most frequently reported issues.

The cardiovascular, respiratory, and gastrointestinal systems were the most affected by these adverse reactions, highlighting the need for monitoring these organ systems during and after the infusion of stem cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse reactions on day zero of hematopoietic stem cell transplantation: integrative review. Figueiredo, TWB., Mercês, NNAD., Nunes, MBM., et al.[2022]

Stem cell therapy (SCT) shows uncertain effects on achieving clinical remission in patients with refractory Crohn's disease, based on a meta-analysis of 7 randomized controlled trials involving 442 participants, indicating a need for further research to clarify its efficacy.

SCT is likely to improve fistula closure in the short and long term compared to standard care, but it may also increase the risk of serious adverse events, highlighting the importance of careful patient monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem cell transplantation for induction of remission in medically refractory Crohn's disease. El-Nakeep, S., Shawky, A., Abbas, SF., et al.[2023]

Citations

1.

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 ...

2.

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 ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4913333/

Stem cell-based therapies in inflammatory bowel disease

One patient was showed to have prolonged clinical remission after high-dose chemotherapy and peripheral-blood stem-cell (PBSC) transplantation for high-risk ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02225795

Pilot Study of Stem Cell Transplantation for Children and ...

Among those, five patients achieved a clinical and endoscopic remission within 6 months after autoPBSCT. However, relapses occurred in 7/9 patients during ...

5.

stemcellres.biomedcentral.com

stemcellres.biomedcentral.com/articles/10.1186/s13287-017-0570-x

the efficacy and safety of stem cell therapy for Crohn's disease

A random-effects meta-analysis of all studies of SCT as systemic infusion showed that 46% (95% CI 25–69, n = 116) of patients achieved clinical ...