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

Recruiting at 38 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

Trial Summary

What is the purpose of this trial?

This study is a prospective randomized placebo-controlled phase 2 study to compare CYP-001 plus corticosteroids (CS) to placebo plus CS in allogeneic hematologic stem cell transplant recipients with HR-aGvHD. Severity of GvHD will be assessed at screening and throughout the study using Mount Sinai Acute GvHD International Consortium (MAGIC) guidelines. Eligible subjects will be randomized to receive either CYP-001 IV infusion on Days 0 and 4 or placebo on the same days. All subjects will receive ongoing CS therapy as appropriate per institutional guidelines. Subjects will have study visits up to Day 100 during the Primary Evaluation Period. During the Follow-Up Period, subjects will have study visits up to 24 months.

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.

What data supports the idea that CYP-001 + Corticosteroids for Graft-versus-Host Disease is an effective treatment?

The available research shows that using mesenchymal stem cells (MSCs), similar to CYP-001, in combination with corticosteroids can be effective for treating Graft-versus-Host Disease, especially when the disease does not respond to steroids alone. In one study, two out of three patients achieved complete remission, and one had partial remission. Another study reported a complete response in seven patients and partial response in four out of twelve patients with acute Graft-versus-Host Disease. These results suggest that adding MSCs to corticosteroid treatment can improve outcomes for patients who do not respond to steroids alone. ^{1 2 3 4 5}

What safety data exists for CYP-001 and corticosteroids in treating graft-versus-host disease?

CYP-001, an iPSC-derived mesenchymal stromal cell product, has been evaluated for safety in a phase I clinical trial for steroid-resistant acute graft-versus-host disease. The trial found CYP-001 to be safe and well-tolerated, with no serious adverse events related to the treatment. Additionally, other studies on mesenchymal stromal cells for similar conditions have shown safety, though with some associated adverse events like hot flashes, headaches, and peripheral neuropathy. Overall, the safety profile of mesenchymal stromal cells, including CYP-001, appears favorable in the context of graft-versus-host disease treatment. ^{2 6 7 8 9}

Is CYP-001 a promising treatment for graft-versus-host disease?

Yes, CYP-001 is a promising treatment for graft-versus-host disease. It is made from special stem cells that can grow and change into different types of cells. In a study, it was safe and helped most patients improve, with 86.7% showing a positive response and 53.3% having a complete recovery by day 100. ^{2 3 8 10 11}

Research Team

Jolanta Airey, MD

Principal Investigator

Cynata Therapeutics Limited

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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]

References

1. China 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]. [2018]

2. Russia (Federation) 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]. [2012]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Adult human mesenchymal stromal cells and the treatment of graft versus host disease. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Treatment of Severe Steroid-Refractory Acute-Graft-vs.-Host Disease With Mesenchymal Stem Cells-Single Center Experience. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

Mesenchymal stromal cell therapy for steroid-refractory acute and chronic graft versus host disease: a phase 1 study. [2021]

6. United States 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. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Adult adherent stromal cells in the management of graft-versus-host disease. [2014]

8. United States 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. [2023]

9. Japan 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. [2022]

10. England 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. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Immunomodulatory effects of mesenchymal stem cells in a rat corneal allograft rejection model. [2022]