Back to resultsA Study of CYP-001 in Combination With Corticosteroids in Adults With High-risk aGvHD
Primary Purpose
Graft Versus Host Disease, Acute
Status
Recruiting
Phase
Phase 2
Locations
Australia
Study Type
Interventional
Intervention
CYP-001: Cymerus induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (MSCs)
Placebo
Corticosteroids
Sponsored by
About this trial
This is an interventional treatment trial for Graft Versus Host Disease, Acute
Eligibility Criteria
Inclusion Criteria: Undergone allogeneic hematopoietic stem cell transplant (HSCT) Clinically diagnosed with acute GvHD requiring systemic therapy with corticosteroids. HR-aGvHD must meet one of the following clinical features within 72 hours prior to randomization: (a) high-risk as per Refined Minnesota Criteria; OR (b) One of the following: (i) isolated stage 2 involvement of the lower GI tract; (ii) Stage 1 lower GI tract disease with skin involvement Evidence of myeloid engraftment post allogeneic HSCT Life expectancy of at least one month Exclusion Criteria: Received any systemic treatment for aGvHD other than corticosteroids +/- calcineurin inhibitors Chronic GvHD or overlap syndrome with both acute and chronic features of GvHD Relapsed primary malignancy since received more than one allogeneic HSCT Clinically significant respiratory, renal or cardiac disease Cholestatic disorders or sinusoidal obstructive syndrome/veno-occlusive disease of the liver Any active uncontrolled infection requiring treatment and likely to impact on the ability of the subject to participate in the trial. Known infection with CMV, EBV, HHV-6, HBV, HCV, HIV or Tuberculosis. If the treatment for CMV, EBV, HHV-6, HBV, HCV has commenced the subject is eligible. Known sensitivity to dimethylsulfoxide (DMSO) or any other component of CYP-001. Received any investigational treatment agent within 30 days or within 5 half-lives of Screening, whichever is greater.
Sites / Locations
- Westmead HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
CYP-001 plus corticosteroids
Placebo plus corticosteroids
Arm Description
Outcomes
Primary Outcome Measures
Overall response rate (ORR)
ORR is defined as the proportion of subjects demonstrating a complete response (CR) or partial response (PR) without requirement for additional systemic therapies for an earlier progression, a mixed response or a nonresponse.
Secondary Outcome Measures
Durable Overall response rate (ORR)
Durable ORR is defined as the proportion of subjects demonstrating OR at Day 28 and maintaining OR at Day 60 and Day 100
Overall response rate (ORR)
ORR is defined as the proportion of subjects demonstrating a CR or PR without requirement for additional systemic therapies for an earlier progression, a mixed response or a nonresponse.
Complete response rate (CRR)
ORR is defined as the proportion of subjects demonstrating a CR without requirement for additional systemic therapies for an earlier progression, a mixed response or a nonresponse.
Overall survival
The Kaplan Meier curve will be used to estimate the distribution of overall survival and the probability of surviving to relevant timepoints.
Event-free survival
Event-Free survival is defined as the time from the date of randomization to the date of hematologic disease relapse/progression, graft failure, or death due to any cause.
Time to non-relapse mortality
Time to non-relapse mortality is defined as the time from the date of randomization to the date of death not preceded by hematologic disease relapse/progression.
Failure-free survival
Failure-free survival is defined as the time from the date of randomization to date of hematologic disease relapse/progression, non-relapse mortality, or addition of new systemic aGvHD treatment
Time to malignancy relapse/progression
Time to malignancy relapse/progression is defined as the time from the date of randomization to the date to hematologic malignancy relapse/progression.
Incidence of chronic GvHD
Chronic GvHD is defined as the diagnosis of mild, moderate, or severe chronic GvHD.
Weekly cumulative steroid dose
The total corticosteroid dose administered each week
Patient reported outcomes: Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) instrument
The FACT-BMT form was designed to measure the quality of life in patients undergoing bone marrow transplantation.
Patient reported outcomes: EuroQol 5-Dimension (EQ-5D) health-related quality of life instrument
EQ-5D is a standardized measure of health-related quality of life
Incidence, severity, duration of treatment-emergent adverse events
Assessment of safety
Full Information
NCT ID
NCT05643638
First Posted
November 29, 2022
Last Updated
August 10, 2023
Sponsor
Cynata Therapeutics Limited
1. Study Identification
Unique Protocol Identification Number
NCT05643638
Brief Title
A Study of CYP-001 in Combination With Corticosteroids in Adults With High-risk aGvHD
Official Title
A Multicenter, Randomized, Double-blind, Placebo-Controlled Phase II Study to Investigate the Efficacy and Safety of CYP-001 in Combination With Corticosteroids vs Corticosteroids Alone for the Treatment of High-Risk Acute Graft Versus Host Disease
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 31, 2023 (Anticipated)
Primary Completion Date
April 30, 2025 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cynata Therapeutics Limited
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft Versus Host Disease, Acute
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CYP-001 plus corticosteroids
Arm Type
Experimental
Arm Title
Placebo plus corticosteroids
Arm Type
Placebo Comparator
Intervention Type
Biological
Intervention Name(s)
CYP-001: Cymerus induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (MSCs)
Intervention Description
Cymerus MSCs are derived from iPSCs using the proprietary Cymerus platform technology.
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
The placebo product is identical to CYP-001, except that it contains no active agent
Intervention Type
Drug
Intervention Name(s)
Corticosteroids
Intervention Description
All enrolled subjects in this trial must receive corticosteroids at a minimum dose of oral prednisone 2 mg/kg/day (or methylprednisolone 1.6 mg/kg/day IV) as therapy for aGvHD for at least for 72 hours post enrollment.
Primary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
ORR is defined as the proportion of subjects demonstrating a complete response (CR) or partial response (PR) without requirement for additional systemic therapies for an earlier progression, a mixed response or a nonresponse.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Durable Overall response rate (ORR)
Description
Durable ORR is defined as the proportion of subjects demonstrating OR at Day 28 and maintaining OR at Day 60 and Day 100
Time Frame
100 days
Title
Overall response rate (ORR)
Description
ORR is defined as the proportion of subjects demonstrating a CR or PR without requirement for additional systemic therapies for an earlier progression, a mixed response or a nonresponse.
Time Frame
100 days
Title
Complete response rate (CRR)
Description
ORR is defined as the proportion of subjects demonstrating a CR without requirement for additional systemic therapies for an earlier progression, a mixed response or a nonresponse.
Time Frame
100 days
Title
Overall survival
Description
The Kaplan Meier curve will be used to estimate the distribution of overall survival and the probability of surviving to relevant timepoints.
Time Frame
2 years
Title
Event-free survival
Description
Event-Free survival is defined as the time from the date of randomization to the date of hematologic disease relapse/progression, graft failure, or death due to any cause.
Time Frame
2 years
Title
Time to non-relapse mortality
Description
Time to non-relapse mortality is defined as the time from the date of randomization to the date of death not preceded by hematologic disease relapse/progression.
Time Frame
2 years
Title
Failure-free survival
Description
Failure-free survival is defined as the time from the date of randomization to date of hematologic disease relapse/progression, non-relapse mortality, or addition of new systemic aGvHD treatment
Time Frame
2 years
Title
Time to malignancy relapse/progression
Description
Time to malignancy relapse/progression is defined as the time from the date of randomization to the date to hematologic malignancy relapse/progression.
Time Frame
2 years
Title
Incidence of chronic GvHD
Description
Chronic GvHD is defined as the diagnosis of mild, moderate, or severe chronic GvHD.
Time Frame
2 years
Title
Weekly cumulative steroid dose
Description
The total corticosteroid dose administered each week
Time Frame
100 days
Title
Patient reported outcomes: Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) instrument
Description
The FACT-BMT form was designed to measure the quality of life in patients undergoing bone marrow transplantation.
Time Frame
2 years
Title
Patient reported outcomes: EuroQol 5-Dimension (EQ-5D) health-related quality of life instrument
Description
EQ-5D is a standardized measure of health-related quality of life
Time Frame
2 years
Title
Incidence, severity, duration of treatment-emergent adverse events
Description
Assessment of safety
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Undergone allogeneic hematopoietic stem cell transplant (HSCT)
Clinically diagnosed with acute GvHD requiring systemic therapy with corticosteroids.
HR-aGvHD must meet one of the following clinical features within 72 hours prior to randomization: (a) high-risk as per Refined Minnesota Criteria; OR (b) One of the following: (i) isolated stage 2 involvement of the lower GI tract; (ii) Stage 1 lower GI tract disease with skin involvement
Evidence of myeloid engraftment post allogeneic HSCT
Life expectancy of at least one month
Exclusion Criteria:
Received any systemic treatment for aGvHD other than corticosteroids +/- calcineurin inhibitors
Chronic GvHD or overlap syndrome with both acute and chronic features of GvHD
Relapsed primary malignancy since
received more than one allogeneic HSCT
Clinically significant respiratory, renal or cardiac disease
Cholestatic disorders or sinusoidal obstructive syndrome/veno-occlusive disease of the liver
Any active uncontrolled infection requiring treatment and likely to impact on the ability of the subject to participate in the trial.
Known infection with CMV, EBV, HHV-6, HBV, HCV, HIV or Tuberculosis. If the treatment for CMV, EBV, HHV-6, HBV, HCV has commenced the subject is eligible.
Known sensitivity to dimethylsulfoxide (DMSO) or any other component of CYP-001.
Received any investigational treatment agent within 30 days or within 5 half-lives of Screening, whichever is greater.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Cynata Project Manager
Phone
+61 3 7067 6940
Email
clinical@cynata.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jolanta Airey, MD
Organizational Affiliation
Cynata Therapeutics Limited
Official's Role
Study Director
Facility Information:
Facility Name
Westmead Hospital
City
Westmead
State/Province
New South Wales
Country
Australia
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
The Sponsor will consider requests to share IPD from this study for further research of a non-commercial nature. Requests should be submitted to clinical@cynata.com. Sharing of IPD will be subjects to the execution of an IPD sharing agreement, and applicable laws, regulations and guidance in force at that time.
IPD Sharing Time Frame
IPD sharing requests will be considered from 12 months after publication of results of this study.
IPD Sharing Access Criteria
Requests for sharing of IPD for non-commercial research purposes will be considered in good faith by the Sponsor. Requests must be accompanied by a detailed research plan, with a justification for the proposed research.
Learn more about this trial
A Study of CYP-001 in Combination With Corticosteroids in Adults With High-risk aGvHD
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