CYP-001 + Corticosteroids for Graft-versus-Host Disease
Recruiting in Palo Alto (17 mi)
+38 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Cynata Therapeutics Limited
Must be taking: Corticosteroids
Must not be taking: Investigational agents
Disqualifiers: Chronic GvHD, Relapsed malignancy, others
Prior Safety Data
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.
12345What 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.
26789Is 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.
2381011Eligibility 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.
+2 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: CYP-001 plus corticosteroidsExperimental Treatment2 Interventions
Group II: Placebo plus corticosteroidsPlacebo Group2 Interventions
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Memorial healthcare SystemPembroke Pines, FL
University of Arkansas Medical CenterLittle Rock, AR
University of UtahSalt Lake City, UT
University Of Nebrasaka Medical CenterOmaha, NE
More Trial Locations
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Who Is Running the Clinical Trial?
Cynata Therapeutics LimitedLead Sponsor
References
[Clinical study of umbilical cord-derived mesenchymal stem cells for treatment of nineteen patients with steroid-resistant severe acute graft-versus-host disease]. [2018]To evaluate the safety and efficacy of umbilical cord-derived mesenchymal stem cells (MSCs) infusion in patients with steroid-resistant severe acute graft-versus-host disease (aGVHD).
[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]To evaluate the efficiency of administration of multipotent mesenchymal stromal cells obtained from a bone marrow donor for the treatment of an acute host-versus-graft reaction (HVGR) resistant to therapy with glucocorticosteroids (GCS).
Adult human mesenchymal stromal cells and the treatment of graft versus host disease. [2021]Graft versus host disease is a difficult and potentially lethal complication of hematopoietic stem cell transplantation. It occurs with minor human leucocyte antigen (HLA) mismatch and is normally treated with corticosteroid and other immunosuppressive therapy. When it is refractory to steroid therapy, mortality approaches 80%. Mesenchymal stromal cells are rare cells found in bone marrow and other tissues. They can be expanded in culture and possess complex and diverse immunomodulatory activity. Moreover, human mesenchymal stromal cells carry low levels of class 1 and no class 2 HLA antigens, making them immunoprivileged and able to be used without HLA matching. Their use in steroid-refractory graft versus host disease was first described in 2004. Subsequently, they have been used in a number of Phase I and II trials in acute and chronic graft versus host disease trials with success. We discuss their mode of action, the results, their production, and potential dangers with a view to future application.
Treatment of Severe Steroid-Refractory Acute-Graft-vs.-Host Disease With Mesenchymal Stem Cells-Single Center Experience. [2022]The most effective treatment of steroid refractory acute graft vs. host disease (aGvHD) is not yet established and mesenchymal stem cells (MSC) appear to be a promising therapy for the condition. We report single center case series of three patients, who underwent allogeneic hematopoietic cell transplantation and later developed steroid refractory graft-vs.-host disease, treated with MSC infusions. Two patients achieved complete remission and one patient partial remission of skin and/or gastrointestinal aGvHD. We demonstrated application of MSC for treatment of severe steroid refractory aGvHD is feasible in clinical practice. Detailed description of patient's features and MSC production protocol is crucial for future comparison on efficacy and safety of cell-based therapies. However, for any substantial conclusions regarding efficacy of MSC higher patient numbers will be required.
Mesenchymal stromal cell therapy for steroid-refractory acute and chronic graft versus host disease: a phase 1 study. [2021]Steroid-refractory acute graft versus host disease (AGVHD) and chronic graft versus host disease (CGVHD) after allogeneic haematopoietic stem cell transplantation are major causes of morbidity and mortality. We undertook a phase I trial in patients with steroid-refractory AGVHD and CGVHD utilising bone marrow-derived mesenchymal stromal cells (MSC). Additionally, all refractory patients were treated with etanercept concomitantly. The primary end point was safety, and secondary end points were best response achieved and overall survival. A median of two infusions per patient were administered. The response rate overall for AGVHD was complete in seven, partial in four and no response in one patient. Of the seven patients who achieved a complete response, six are alive. The actuarial survival for the overall group of AGVHD was 55% at 30 months. Two patients with CGVHD achieved complete response with two partial responses and three with no response. The survival for those with AGVHD who achieved a complete response compared with those who did not was significant (p = 0.03). We identified no early or late safety issues in the nineteen patients. In view of the poor outlook for steroid-refractory AGVHD, further trials are warranted of MSC with steroid therapy, at the onset of AGVHD before steroid resistance.
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]The immunosuppressive properties of mesenchymal stromal cells (MSC) have been successfully tested to control clinical severe graft-versus host disease and improve survival. However, clinical studies have not yet provided conclusive evidence of their efficacy largely because of lack of patients' stratification criteria. The heterogeneity of MSC preparations is also a major contributing factor, as manufacturing of therapeutic MSC is performed according to different protocols among different centers. Understanding the variability of the manufacturing protocol would allow a better comparison of the results obtained in the clinical setting among different centers. In order to acquire information on MSC manufacturing we sent a questionnaire to the European Society for Blood and Marrow Transplantation centers registered as producing MSC. Data from 17 centers were obtained and analyzed by means of a 2-phase questionnaire specifically focused on product manufacturing. Gathered information included MSC tissue sources, MSC donor matching, medium additives for ex vivo expansion, and data on MSC product specification for clinical release. The majority of centers manufactured MSC from bone marrow (88%), whilst only 2 centers produced MSC from umbilical cord blood or cord tissue. One of the major changes in the manufacturing process has been the replacement of fetal bovine serum with human platelet lysate as medium supplement. 59% of centers used only third-party MSC, whilst only 1 center manufactured exclusively autologous MSC. The large majority of these facilities (71%) administered MSC exclusively from frozen batches. Aside from variations in the culture method, we found large heterogeneity also regarding product specification, particularly in the markers used for phenotypical characterization and their threshold of expression, use of potency assays to test MSC functionality, and karyotyping. The initial data collected from this survey highlight the variability in MSC manufacturing as clinical products and the need for harmonization. Until more informative potency assays become available, a more homogeneous approach to cell production may at least reduce variability in clinical trials and improve interpretation of results.
Adult adherent stromal cells in the management of graft-versus-host disease. [2014]Early reports demonstrated the safety of adherent mesenchymal stromal cell (MSC) infusions in the hematopoietic stem cell transplantation (HCT) setting, as well as clinical efficacy for treatment of steroid refractory acute graft-versus-host disease (GVHD); however, two large, Phase III randomized, placebo-controlled trials of MSC for initial therapy or steroid refractory GVHD failed to meet their primary endpoints of durable complete response. Subset analyses demonstrated efficacy in selected patient populations, contributing to recent approvals of MSC for pediatric patients in Canada and New Zealand.
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]The therapeutic potential of donor-derived mesenchymal stromal cells (MSCs) has been investigated in diverse diseases1, including steroid-resistant acute graft versus host disease (SR-aGvHD)2. However, conventional manufacturing approaches are hampered by challenges with scalability and interdonor variability, and clinical trials have shown inconsistent outcomes3,4. Induced pluripotent stem cells (iPSCs) have the potential to overcome these challenges, due to their capacity for multilineage differentiation and indefinite proliferation5,6. Nonetheless, human clinical trials of iPSC-derived cells have not previously been completed. CYP-001 (iPSC-derived MSCs) is produced using an optimized, good manufacturing practice (GMP)-compliant manufacturing process. We conducted a phase 1, open-label clinical trial (no. NCT02923375) in subjects with SR-aGvHD. Sixteen subjects were screened and sequentially assigned to cohort A or cohort B (n = 8 per group). One subject in cohort B withdrew before receiving CYP-001 and was excluded from analysis. All other subjects received intravenous infusions of CYP-001 on days 0 and 7, at a dose level of either 1 × 106 cells per kg body weight, to a maximum of 1 × 108 cells per infusion (cohort A), or 2 × 106 cells per kg body weight, to a maximum dose of 2 × 108 cells per infusion (cohort B). The primary objective was to assess the safety and tolerability of CYP-001, while the secondary objectives were to evaluate efficacy based on the proportion of participants who showed a complete response (CR), overall response (OR) and overall survival (OS) by days 28/100. CYP-001 was safe and well tolerated. No serious adverse events were assessed as related to CYP-001. OR, CR and OS rates by day 100 were 86.7, 53.3 and 86.7%, respectively. The therapeutic application of iPSC-derived MSCs may now be explored in diverse inflammatory and immune-mediated diseases.
Immunological influence of serum-free manufactured umbilical cord-derived mesenchymal stromal cells for steroid-resistant acute graft-versus-host disease. [2022]This study investigated the safety, efficacy, and immunological influence of allogeneic umbilical cord-derived mesenchymal stromal cells (IMSUT-CORD) processed in serum-free medium and cryoprotectant, for treating steroid-resistant acute graft-versus-host disease (aGVHD). In a phase I dose-escalation trial, IMSUT-CORD were infused intravenously twice weekly over two cycles with up to two additional cycles. Four patients received a dose of 1 × 106 cells/kg, while three received 2 × 106/kg. Of 76 total adverse events, fourteen associated or possibly associated adverse events included 2 cases of a hot flash, headache, and peripheral neuropathy, 1 each of upper abdominal pain, hypoxia, increased γ-GTP, somnolence, peripheral vascular pain at the injection site, thrombocytopenia, hypertension, and decreased fibrinogen. At 16 weeks after the initial IMSUT-CORD infusion, three patients showed complete response (CR), two partial response (PR), one mixed response, and one no response. The overall response rate was 71.4%, and the continuous CR/PR rate was 100% for over 28 days after CR/PR. NK cell count significantly increased and correlated with treatment response, whereas IL-12, IL-17, and IL-33 levels decreased, but did not correlate with treatment response. CCL2 and CCL11 levels increased during IMSUT-CORD therapy. IMSUT-CORD are usable in patients with steroid-resistant aGVHD (UMIN000032819: https://www.umin.ac.jp/ctr ).
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]Steroid-resistant (SR) acute graft-versus-host disease (aGVHD) lacks standard second-line treatment. Mesenchymal stromal cells (MSCs) have potential efficacy in SR aGVHD. We aimed to assess the efficacy and safety of MSCs combined with basiliximab and calcineurin inhibitor as second-line therapy for SR aGVHD.
Immunomodulatory effects of mesenchymal stem cells in a rat corneal allograft rejection model. [2022]Mesenchymal stem cells (MSCs) are promising candidates for immunomodulatory therapy that are currently being tested in several organ transplant rejection models. In this study, we tested the immunomodulatory effects of MSC injection in a rat model of corneal allograft rejection. MSCs were isolated and cultured from bone marrow of Wistar rats. A rat corneal allograft rejection model was established using Wistar rats as donors and Lewis rats as recipients. Lewis rats were randomly separated into 12 groups and treated with MSCs alone or MSCs combined with Cyclosporin A (CsA) at different doses. In MSC-treated rats, the T cell response to ConA was evaluated, Th1/Th2 cytokines produced by T lymphocytes were measured, and the number of CD4+CD25+Foxp3+ regulatory T cells (Treg) was assessed. Results demonstrated that postoperative injection of MSCs prolonged graft survival time. MSCs significantly inhibited proliferation of pathogenic T cells in vitro and prevented T cell response in vivo (p