CYP-001 + Corticosteroids for Graft-versus-Host Disease

Recruiting at 45 trial locations

Overseen By Cynata Project Manager

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Cynata Therapeutics Limited

Must be taking: Corticosteroids

Must not be taking: Investigational agents

Disqualifiers: Chronic GvHD, Relapsed malignancy, others

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

Compensation: Varies

Number of Visits: 126

Duration: 4 days

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CYP-001, a type of mesenchymal stem cell therapy, combined with standard corticosteroids to help people with graft-versus-host disease (GvHD). GvHD can occur after a stem cell transplant when donated cells attack the recipient's body, causing issues like skin rashes or gut problems. Participants will receive either CYP-001 or a placebo (inactive substance) along with their usual corticosteroids. The study seeks individuals who have undergone a stem cell transplant and are experiencing acute GvHD that requires systemic therapy. The trial will evaluate the treatment's effectiveness and monitor participants for up to 24 months. As a Phase 2 trial, the research focuses on assessing the treatment's efficacy in an initial, smaller group of people.

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

The trial does not specify if you need to stop your current medications. However, you must not have received any systemic treatment for aGvHD other than corticosteroids or calcineurin inhibitors. You also cannot have taken any investigational treatment within 30 days or 5 half-lives before screening.

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

Research has shown that CYP-001, when used with corticosteroids, is generally safe and well-tolerated. Studies found no serious side effects linked to CYP-001, such as severe health issues or tumors.

In one study, 60% of patients taking CYP-001 survived for two years without major safety problems. Overall, the evidence suggests that CYP-001 is safe for people, especially for conditions that do not respond well to steroids. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for GvHD?

Researchers are excited about CYP-001 because it offers a new approach to treating graft-versus-host disease (GVHD). Unlike the standard treatment, which primarily relies on corticosteroids to suppress the immune response, CYP-001 is derived from mesenchymal stem cells. This innovative mechanism targets the inflammation and tissue damage caused by GVHD more directly, potentially offering a more effective and targeted therapy. Additionally, CYP-001 could reduce reliance on corticosteroids, which are known for their significant side effects. This combination of a novel mechanism and reduced side effects is why researchers are eager to explore CYP-001’s potential in managing GVHD.

What evidence suggests that CYP-001 plus corticosteroids could be an effective treatment for GvHD?

Research has shown that CYP-001, one of the treatments in this trial, may help treat steroid-resistant graft-versus-host disease (GvHD) when combined with corticosteroids. In earlier studies, 60% of patients who received CYP-001 survived for two years, surpassing typical outcomes for severe GvHD. Made from stem cells, CYP-001 has proven safe and well tolerated. Early results are promising, suggesting it could help manage GvHD symptoms. Participants in this trial will receive either CYP-001 plus corticosteroids or a placebo plus corticosteroids. ^{2 3 5 6 7}

Who Is on the Research Team?

Jolanta Airey, MD

Principal Investigator

Cynata Therapeutics Limited

Are You a Good Fit for This Trial?

This trial is for adults who've had a stem cell transplant and are now facing high-risk acute Graft-versus-Host Disease (aGvHD). They should expect to live at least another month, have specific types of lower GI tract involvement or skin issues, need corticosteroids for their aGvHD, and show signs that the new stem cells are working in their bone marrow.

Inclusion Criteria

I have had a stem cell transplant from a donor.

You are expected to live for at least one more month.

My condition meets the high-risk criteria for acute GvHD as defined, including specific GI and skin involvement.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CYP-001 or placebo infusion on Days 0 and 4, along with ongoing corticosteroid therapy

4 days

2 visits (in-person)

Primary Evaluation Period

Participants are monitored for overall response rate and other outcomes up to Day 100

14 weeks

Regular visits up to Day 100

Follow-up

Participants are monitored for safety, effectiveness, and long-term outcomes

24 months

Regular visits up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Corticosteroids
• CYP-001

Trial Overview The study tests CYP-001, which comes from special lab-grown stem cells. It's given with standard corticosteroid treatment to see if it's better than just getting a placebo with corticosteroids. Patients will be randomly chosen to get either CYP-001 or the placebo on two separate days and followed up for up to two years.

How Is the Trial Designed?

Group I: CYP-001 plus corticosteroids Experimental Treatment 2 Interventions

Group II: Placebo plus corticosteroids Placebo Group 2 Interventions

Who Is Running the Clinical Trial?

Cynata Therapeutics Limited

Lead Sponsor

Trials

4

Recruited

120+

Published Research Related to This Trial

In a case series of three patients with steroid refractory acute graft vs. host disease (aGvHD) treated with mesenchymal stem cell (MSC) infusions, two patients achieved complete remission and one achieved partial remission, indicating potential efficacy of MSC therapy.

The study highlights the feasibility of using MSCs in clinical practice for severe aGvHD, but emphasizes the need for larger patient studies to draw more definitive conclusions about the efficacy and safety of this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Severe Steroid-Refractory Acute-Graft-vs.-Host Disease With Mesenchymal Stem Cells-Single Center Experience. Česen Mazič, M., Girandon, L., Kneževič, M., et al.[2022]

CYP-001, derived from induced pluripotent stem cells (iPSCs), was found to be safe and well tolerated in a phase 1 clinical trial involving 16 subjects with steroid-resistant acute graft versus host disease (SR-aGvHD), with no serious adverse events related to the treatment.

The trial showed promising efficacy results, with an overall response rate of 86.7%, a complete response rate of 53.3%, and an overall survival rate of 86.7% by day 100, suggesting that iPSC-derived MSCs could be a viable treatment option for various inflammatory and immune-mediated diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Production, safety and efficacy of iPSC-derived mesenchymal stromal cells in acute steroid-resistant graft versus host disease: a phase I, multicenter, open-label, dose-escalation study. Bloor, AJC., Patel, A., Griffin, JE., et al.[2023]

A survey of 17 European centers revealed significant variability in the manufacturing processes of mesenchymal stromal cells (MSCs), which could impact their clinical efficacy in treating conditions like severe graft-versus-host disease.

Most centers used bone marrow as the source for MSCs and have shifted from fetal bovine serum to human platelet lysate for cell culture, highlighting the need for standardized protocols to improve consistency and comparability in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Manufacturing Mesenchymal Stromal Cells for the Treatment of Graft-versus-Host Disease: A Survey among Centers Affiliated with the European Society for Blood and Marrow Transplantation. Trento, C., Bernardo, ME., Nagler, A., et al.[2022]

Mesenchymal stromal cell (MSC) infusions have shown safety in hematopoietic stem cell transplantation and some efficacy in treating steroid refractory acute graft-versus-host disease (GVHD), but large Phase III trials did not achieve their primary endpoints for durable complete response.

Recent approvals for MSC use in pediatric patients in Canada and New Zealand highlight the potential for targeted applications, although ongoing research is needed to clarify optimal infusion methods and patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adult adherent stromal cells in the management of graft-versus-host disease. Newell, LF., Deans, RJ., Maziarz, RT.[2014]

Infusion of umbilical cord-derived mesenchymal stem cells (MSCs) in 19 patients with steroid-resistant severe acute graft-versus-host disease (aGVHD) showed promising results, with 11 patients achieving a complete response and 4 a partial response, indicating the treatment's efficacy.

The MSC infusions were safe, with no immediate side effects reported and no evidence of tumor formation, suggesting that this therapy could be a viable option for patients with severe aGVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical study of umbilical cord-derived mesenchymal stem cells for treatment of nineteen patients with steroid-resistant severe acute graft-versus-host disease]. Chen, GH., Yang, T., Tian, H., et al.[2018]

Mesenchymal stromal cells (MSCs) show promise as a treatment for steroid-refractory graft versus host disease (GVHD), a serious complication of hematopoietic stem cell transplantation, with successful outcomes reported in Phase I and II trials.

MSCs are immunoprivileged due to their low levels of HLA antigens, allowing them to be used without HLA matching, which could significantly improve treatment options for patients with GVHD who do not respond to conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adult human mesenchymal stromal cells and the treatment of graft versus host disease. Herrmann, RP., Sturm, MJ.[2021]

In a study involving 6 patients with acute host-versus-graft reaction (HVGR) resistant to glucocorticosteroid therapy, the administration of multipotent mesenchymal stromal cells (MMSC) showed effectiveness in 5 out of 6 cases.

After 4 weeks of treatment, 3 patients had a complete or partial response, and 2 showed clinical improvement, indicating that MMSC therapy could be a promising alternative for managing GCS-resistant HVGR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of acute host-versus-graft reaction in patients after allogeneic hematopoietic cell transplantation with multipotent mesenchymal stromal cells from a bone marrow donor]. Petinati, NA., Kuz'mina, LA., Parovichnikova, EN., et al.[2012]

In a phase 3 trial involving 203 patients with steroid-resistant acute graft-versus-host disease (aGVHD), the addition of mesenchymal stromal cells (MSCs) to standard second-line therapy significantly improved overall response rates at day 28 (82.8% vs. 70.7%) and at day 56 (78.8% vs. 64.6%).

The MSC treatment not only enhanced efficacy but also reduced the incidence of chronic graft-versus-host disease (cGVHD) and drug-related toxicity, with no increase in tumor relapse rates, indicating that MSCs are a safe and effective second-line treatment option for aGVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stromal cells plus basiliximab, calcineurin inhibitor as treatment of steroid-resistant acute graft-versus-host disease: a multicenter, randomized, phase 3, open-label trial. Zhao, K., Lin, R., Fan, Z., et al.[2022]

Mesenchymal stem cells (MSCs) significantly prolonged graft survival in a rat model of corneal allograft rejection by inhibiting pathogenic T cell proliferation and enhancing regulatory T cell (Treg) levels, indicating their potential as an effective immunomodulatory therapy.

The combination of MSCs with low-dose Cyclosporin A (CsA) accelerated graft rejection, while a higher dose of CsA (2 mg/kg) alongside MSCs significantly improved graft survival, suggesting that the dosage of CsA is critical in determining the outcome of combined therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulatory effects of mesenchymal stem cells in a rat corneal allograft rejection model. Jia, Z., Jiao, C., Zhao, S., et al.[2022]

In a phase I trial involving 19 patients with steroid-refractory acute graft versus host disease (AGVHD) and chronic graft versus host disease (CGVHD), treatment with bone marrow-derived mesenchymal stromal cells (MSC) showed promising safety, with no early or late safety issues reported.

The treatment resulted in a 55% survival rate at 30 months for AGVHD patients, with significant survival benefits for those who achieved a complete response, highlighting the potential efficacy of MSC therapy in this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stromal cell therapy for steroid-refractory acute and chronic graft versus host disease: a phase 1 study. Herrmann, R., Sturm, M., Shaw, K., et al.[2021]

The study demonstrated that allogeneic umbilical cord-derived mesenchymal stromal cells (IMSUT-CORD) are safe and effective for treating steroid-resistant acute graft-versus-host disease (aGVHD), with an overall response rate of 71.4% among seven patients in a phase I trial.

After treatment, three patients achieved a complete response, and the therapy was associated with significant increases in NK cell counts, suggesting a potential immunological mechanism of action linked to the treatment's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunological influence of serum-free manufactured umbilical cord-derived mesenchymal stromal cells for steroid-resistant acute graft-versus-host disease. Nagamura-Inoue, T., Kato, S., Najima, Y., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02923375

A Study of CYP-001 for the Treatment of Steroid-Resistant ... The purpose of this study is to assess the safety, tolerability and efficacy of two infusions of CYP-001 in adults with steroid-resistant GvHD.

2. nature.com nature.com/articles/s41591-024-02990-z

Two-year safety outcomes of iPS cell-derived ... We now report results at the 2-year follow-up: 9 of 15 (60%) participants survived, which compares favorably with previously reported outcomes ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32929265/

a phase I, multicenter, open-label, dose-escalation study CYP-001 (iPSC-derived MSCs) is produced using an optimized, good manufacturing practice (GMP)-compliant manufacturing process.

4. astctjournal.org astctjournal.org/article/S1083-8791(18)31080-2/fulltext

CYP-001 in Steroid-Resistant Acute GvHD In conclusion, CYP-001 infusions were found to be safe and well tolerated in this study, and we believe the encouraging treatment response and overall survival ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0006497119406629

A Phase I Trial of iPSC-Derived MSCs (CYP-001) in ... This is a multi-center, open label, dose escalation study to assess the safety, tolerability and efficacy of CYP-001 in adults with grade II-IV ...

6. firstwordpharma.com firstwordpharma.com/story/5859663

Further CYP-001 GvHD Clinical Data Published in Nature ... Key results include a two-year overall survival rate of 60% (9/15 patients), with no treatment-related serious adverse events or safety concerns ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38778211/

Two-year safety outcomes of iPS cell-derived ... There were no serious adverse events, tumors or other safety concerns related to CYP-001. In conclusion, systemic delivery of iPS cell-derived cells was safe ...