Vedolizumab Post-Stem Cell Transplant for Crohn's Disease

Overseen By Aaron Etra, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Aaron Etra

Must not be taking: Cyclophosphamide, Thymoglobulin

Disqualifiers: Pregnancy, Age <18, HIV, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treating Crohn's disease, which causes inflammation in the stomach and intestines and can be very painful and disabling. The study combines an autologous stem cell transplant with the drug Vedolizumab to determine if this combination can help patients achieve and maintain remission, a period without symptoms. It targets those whose Crohn's disease remains active and hasn't responded well to treatments like corticosteroids or anti-TNF drugs. Participants will undergo a stem cell transplant followed by Vedolizumab to help restore their immune system and improve health. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

Yes, participants will need to taper off their current medications before undergoing stem cell mobilization as part of the trial process.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Vedolizumab is generally safe for adults who have undergone stem cell transplants. In one study, patients taking this medication experienced few serious gut-related side effects, indicating it rarely causes stomach or intestinal problems. Vedolizumab targets specific cells in the gut to reduce swelling, helping to avoid unwanted effects on other parts of the body. Overall, evidence suggests that Vedolizumab can be safely used after stem cell transplants. ^{1 2 3 4 5}

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

Researchers are excited about the potential of using Vedolizumab after an autologous stem cell transplant for Crohn's Disease because it offers a novel approach compared to current treatments. Most existing therapies, like biologics, aim to suppress the immune system broadly to reduce inflammation. However, Vedolizumab is unique because it specifically targets the gut, potentially reducing systemic side effects. Additionally, pairing it with a stem cell transplant might offer a long-term solution by resetting the immune system, which is something standard treatments cannot achieve on their own. This combination could lead to better management of Crohn's Disease with fewer side effects and more durable remission.

What evidence suggests that this trial's treatments could be effective for Crohn's disease?

Research has shown that Vedolizumab, administered to participants in this trial following a stem cell transplant, may help more patients with Crohn's Disease remain in remission. One study found that 92% of patients stayed in remission from inflammatory bowel disease (IBD) without needing additional medication. Furthermore, Vedolizumab significantly improved survival rates without causing severe stomach or intestinal issues after transplants. These findings suggest that Vedolizumab could be a promising option for maintaining Crohn's Disease remission after a stem cell transplant. ^{2 3 6 7 8}

Who Is on the Research Team?

Aaron Etra, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Louis Cohen, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for adults with active Crohn's Disease who haven't responded to standard treatments like corticosteroids, immunosuppressants, or biologics. They should not have heart, lung issues (like needing extra oxygen), HIV, a history of bad reactions to the trial drugs, be pregnant/breastfeeding, or too sick to do daily activities.

Inclusion Criteria

I cannot have surgery due to the risk of severe digestive issues or because I chose not to.

I have been diagnosed with Crohn's disease.

My bowel disease is active, as confirmed by a specific test.

Exclusion Criteria

History of significant toxicity to any medications used in trial (cyclophosphamide, thymoglobulin, vedolizumab)

HIV infected

Patients for whom an insufficient number of stem cells (<2 X 10^6/kg) have been collected

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Stem Cell Mobilization

Patients undergo stem cell mobilization involving low dose chemotherapy and growth factors, requiring 1-2 week hospitalization.

1-2 weeks

Hospitalization

Stem Cell Transplant

Patients undergo stem cell transplant involving high dose chemotherapy, requiring a 2-4 week hospitalization.

2-4 weeks

Hospitalization

Vedolizumab Maintenance

Patients receive vedolizumab per standard dosing (0, 2, 6 then every 8 weeks) for a total of 8 doses.

6 months

Monthly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment, including repeat colonoscopy and MR/CT scan at 6 months.

6 months

Monthly visits

What Are the Treatments Tested in This Trial?

Interventions

• Autologous stem cell transplant
• Cyclophosphamide
• Methylprednisolone
• Thymoglobulin
• Vedolizumab

Trial Overview The study tests if combining an autologous stem cell transplant with drugs like Thymoglobulin and Cyclophosphamide followed by Vedolizumab can help achieve and maintain remission in Crohn's Disease. It involves hospital stays for chemotherapy and monitoring after the transplant.

How Is the Trial Designed?

Group I: Experimental Experimental Treatment 5 Interventions

Hematopoietic Stem Cell Transplant followed by maintenance Vedolizumab

Autologous stem cell transplant is already approved in European Union, United States for the following indications:

Approved in European Union as Autologous Hematopoietic Stem Cell Transplantation for:

• Severe Crohn's disease
• Perianal fistulas

Approved in United States as Autologous Hematopoietic Stem Cell Transplantation for:

• Clinical trials only; not FDA-approved for Crohn's disease

Who Is Running the Clinical Trial?

Aaron Etra

Lead Sponsor

Trials

1

Recruited

50+

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Published Research Related to This Trial

Rabbit-derived antithymocyte globulin (ATG) can induce a strong immune response in patients, leading to the production of antibodies against specific rabbit glycoprotein epitopes, which may compromise its effectiveness in treating conditions like type 1 diabetes.

The study found that patients developed significant levels of antibodies against these rabbit-specific epitopes after ATG treatment, suggesting that using IgGs without these xenoantigens could enhance the safety and efficacy of ATG therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-Gal and Anti-Neu5Gc Responses in Nonimmunosuppressed Patients After Treatment With Rabbit Antithymocyte Polyclonal IgGs. Salama, A., Evanno, G., Lim, N., et al.[2022]

In a study involving pediatric renal transplant recipients, anti-T-cell induction therapy with polyclonal antibodies, specifically thymoglobulin (Thy), showed equal or greater suppression of T-cells compared to other agents like ATG and ALG after 10 days, indicating its potential effectiveness in improving renal allograft survival.

The study involved 30 participants aged 2 to 18 years, and the results suggest that a shorter 5-day course of Thy may be as effective as a longer 10-day course of ATG or ALG in suppressing T-cell activity, which is crucial for preventing organ rejection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of polyclonal induction agents in pediatric renal transplantation. Brophy, PD., Thomas, SE., McBryde, KD., et al.[2021]

In a study of 408 patients undergoing haploidentical hematopoietic stem cell transplantation, a lower dose of 7.5 mg/kg rabbit antithymocyte globulin (ATG) significantly reduced the incidence of EBV DNAemia and CMV DNAemia compared to the higher dose of 10.0 mg/kg, without increasing the risk of graft-versus-host disease (GVHD).

The 7.5 mg/kg ATG group showed higher counts of EBV- and CMV-specific cytotoxic T cells early after transplantation, suggesting that this lower dose may enhance immune response while minimizing infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two dose levels of rabbit antithymocyte globulin as graft-versus-host disease prophylaxis in haploidentical stem cell transplantation: a multicenter randomized study. Lin, R., Wang, Y., Huang, F., et al.[2020]

In a systematic review of 26 studies involving 3601 patients, lower doses of rabbit thymoglobulin (rATG) at ≤4.5 mg/kg were linked to reduced rates of acute rejection and infections, while maintaining similar rates of graft function and patient survival compared to higher doses.

Doses of rATG between 3-4.5 mg/kg showed the best outcomes, suggesting that using lower doses can be just as effective while minimizing potential side effects in kidney transplant recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between cumulative rATG induction doses and kidney graft outcomes and adverse effects in kidney transplant patients: a systematic review and meta-analysis. Mohammadi, K., Khajeh, B., Dashti-Khavidaki, S., et al.[2022]

In a study of 352 patients undergoing HLA-mismatched allogeneic hematopoietic stem cell transplantation, low to medium doses of rabbit anti-thymocyte globulin (ATG) (2.5 to 7.5 mg/kg) were associated with higher 5-year overall survival rates compared to other doses.

Patients receiving low to medium doses of ATG also experienced lower rates of extensive chronic graft-versus-host disease (ecGVHD), suggesting that these doses improve patient outcomes without increasing relapse rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical impact of anti-thymocyte globulin on survival and graft-versus-host disease in patients undergoing human leukocyte antigen mismatched allogeneic stem cell transplantation. Kim, T., Choi, Y., Lee, JH., et al.[2021]

A systematic review of 6 phase III randomized controlled trials found that rabbit antithymocyte globulin (ATG) formulations, particularly anti-T lymphocyte globulin (ATLG), are effective in preventing graft-versus-host disease (GVHD) after allogeneic stem cell transplantation, showing significantly better outcomes compared to standard treatments.

While both ATLG and Thymoglobulin (Thymo) had similar effects on transplantation-related mortality, Thymo showed a trend towards better overall survival, suggesting that Thymo may be a preferable option for improving long-term survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Different Rabbit Anti-Thymocyte Globulin Formulations in Allogeneic Stem Cell Transplantation: Systematic Literature Review and Network Meta-Analysis. Gagelmann, N., Ayuk, F., Wolschke, C., et al.[2018]

Thymoglobulin is a safe and effective treatment for preventing acute rejection in organ transplantation, with common side effects including cytokine release syndrome and thrombocytopenia, but recent studies suggest that antiviral prophylaxis can mitigate the risk of cytomegalovirus disease associated with its use.

Thymoglobulin may offer advantages over horse ATG in treating aplastic anemia and can reduce the incidence of acute and chronic graft-versus-host disease (GvHD) in patients receiving stem cell transplants, indicating its potential as a versatile immunosuppressant in various therapeutic contexts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thymoglobulin--new approaches to optimal outcomes. Moicean, AD., Popp, AM., Sinescu, I.[2021]

In a study involving 88 simultaneous pancreas/kidney (SPK) transplant recipients, the addition of an anti-CD25 monoclonal antibody to thymoglobulin induction therapy delayed the return of CD25+ T cells by 45 days compared to kidney transplant recipients receiving thymoglobulin alone.

This approach may help reduce the presence of donor-specific T effector cells at the time of transplantation, potentially improving transplant outcomes and reducing the risk of rejection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of anti-CD25 to thymoglobulin for induction therapy: delayed return of peripheral blood CD25-positive population. Sageshima, J., Ciancio, G., Gaynor, JJ., et al.[2018]

Thymoglobulin (TG) and ATG-Fresenius (ATG-F) rapidly bind to various receptors on dendritic cells (DCs), leading to significant immunosuppressive effects, including the induction of apoptosis in both immature and mature DCs.

These ATGs inhibit important functions of DCs, such as antigen uptake and the production of interleukin-12p70, which reduces their ability to stimulate T cells, highlighting their role as targets for immunosuppression in transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antithymocyte globulins suppress dendritic cell function by multiple mechanisms. Naujokat, C., Berges, C., Fuchs, D., et al.[2016]

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Outcomes of Allogeneic Hematopoietic Stem Cell ... At most recent follow-up, 92% of patients achieved sustained medication-free remission of IBD and 60% with prior ostomy underwent re-anastomosis ...

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Autologous Stem Cell Transplant for Crohn's Disease The ENACT study demonstrated a 6% improvement in clinical response in patients receiving natalizumab compared to placebo (56% vs 49%, p = 0.05) in 905 patients ...

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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.

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Vedolizumab for the prevention of intestinal acute GVHD ... Vedolizumab is a gut-selective anti-α 4 β 7 integrin monoclonal antibody that reduces gut inflammation by inhibiting migration of GI-homing T lymphocytes.