Back to resultsA Study of CYP-001 for the Treatment of Steroid-Resistant Acute Graft Versus Host Disease
Primary Purpose
Graft vs Host Disease
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Mesenchymoangioblast-derived mesenchymal stem cells
Sponsored by
About this trial
This is an interventional treatment trial for Graft vs Host Disease
Eligibility Criteria
Inclusion Criteria:
- Diagnosis using consensus grading with steroid-resistant Grade II-IV acute GvHD, after a haematopoietic stem cell transplant for a haematological disorder.
- Life expectancy of at least one month.
- Agree to have follow-up data collected for two years after their initial dose of CYP-001 (under a separate protocol).
Exclusion Criteria:
- Pregnant or breastfeeding or plan to become pregnant within three months of receiving their last dose of CYP-001.
- Have received any investigational research agent within 30 days or five half-lives (whichever is longer) prior to the first dose of IMP.
- Known or suspected current alcohol or substance abuse problem.
- Progressive or relapsing haematological malignancy, a current solid tumour, or previous malignant solid tumour that is likely to recur during the period of the study (with the exception of a past history of basal or squamous cell carcinomas).
- Heart failure (NYHA Functional Class II-IV) and/or pulmonary failure.
- Haemodynamically unstable and/or at high risk of cardiovascular events.
- Terminal organ failure.
- Meningitis, pneumonia with hypoxemia, HIV or another severe or uncontrolled systemic infection, which in the opinion of the investigator is likely to impact on the ability of the patient to participate in the trial.
Sites / Locations
- Sydney Local Health District
- Royal Adelaide Hospital
- NHS Foundation Trust
- NHS Trust
- NHS Foundation Trust
- NHS Foundation Trust
- NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort A
Cohort B
Arm Description
Mesenchymoangioblast-derived mesenchymal stem cells (CYP-001) at a dose of 1 million cells/kg (up to a maximum of 100 million cells) by IV infusion on two occasions (Day 0 and Day 7)
Mesenchymoangioblast-derived mesenchymal stem cells (CYP-001) at a dose of 2 million cells/kg (up to a maximum of 200 million cells) by IV infusion on two occasions (Day 0 and Day 7)
Outcomes
Primary Outcome Measures
Incidence and severity of treatment emergent adverse events [safety and tolerability]
Safety
Incidence and severity of serious adverse events deemed possibly related to CYP-001 [safety and tolerability]
Safety
Secondary Outcome Measures
Complete Response by Day 28
Proportion of participants who show a Complete Response (absence of any signs or symptoms of GvHD) by Day 28
Partial Response by Day 28
Proportion of participants who show a Partial Response (improvement in the severity of GvHD by at least one grade compared to baseline) by Day 28
Overall Survival at Day 28
Proportion of participants who survive until Day 28
Complete Response by Day 100
Proportion of participants who show a Complete Response by Day 100
Partial Response by Day 100
Proportion of participants who show a Partial Response by Day 100
Overall Survival at Day 100
Proportion of participants who survive until Day 100
Full Information
NCT ID
NCT02923375
First Posted
October 3, 2016
Last Updated
August 8, 2020
Sponsor
Cynata Therapeutics Limited
1. Study Identification
Unique Protocol Identification Number
NCT02923375
Brief Title
A Study of CYP-001 for the Treatment of Steroid-Resistant Acute Graft Versus Host Disease
Official Title
An Open-Label Phase 1 Study to Investigate the Safety and Efficacy of CYP-001 for the Treatment of Adults With Steroid-Resistant Acute Graft Versus Host Disease
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
March 1, 2017 (Actual)
Primary Completion Date
August 28, 2018 (Actual)
Study Completion Date
June 30, 2020 (Actual)
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
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
This is a multi-centre, open label, dose escalation study to assess the safety, tolerability and efficacy of two infusions of CYP-001, in adults who have steroid-resistant GvHD.
Participants will receive standard of care treatment throughout the study, according to local procedures. The first eight participants will be enrolled in Cohort A and receive a CYP-001 dose of 1 million cells per kg, up to a maximum dose of 100 million cells, on Day 0 and Day 7. Subject to a safety review of data from Cohort A, an additional eight participants will be enrolled into Cohort B and receive a CYP-001 dose of 2 million cells/kg, up to a maximum dose of 200 million cells, on Day 0 and Day 7. The primary evaluation period concludes for each participant 100 days after the first dose of CYP-001. Participants will have study visits on Days 0, 3, 7, 14, 21, 28, 60 and 100. Subsequently, participants will enter a long term follow-up period, which concludes 2 years after the first dose of CYP-001.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft vs Host Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort A
Arm Type
Experimental
Arm Description
Mesenchymoangioblast-derived mesenchymal stem cells (CYP-001) at a dose of 1 million cells/kg (up to a maximum of 100 million cells) by IV infusion on two occasions (Day 0 and Day 7)
Arm Title
Cohort B
Arm Type
Experimental
Arm Description
Mesenchymoangioblast-derived mesenchymal stem cells (CYP-001) at a dose of 2 million cells/kg (up to a maximum of 200 million cells) by IV infusion on two occasions (Day 0 and Day 7)
Intervention Type
Biological
Intervention Name(s)
Mesenchymoangioblast-derived mesenchymal stem cells
Other Intervention Name(s)
CYP-001
Intervention Description
The active agent in CYP-001 is allogeneic mesenchymoangioblast-derived mesenchymal stem cells (MCA-derived MSCs), which are produced using the proprietary Cymerus™ platform technology. Cymerus™ refers to the process of generating cell-based products from intermediate cells, MCAs, which in turn are derived from induced pluripotent stem cells or iPSCs. The iPSCs used in the Cymerus™ process were derived from blood donated by a fully-consented healthy adult donor, and were reprogrammed using a transgene-free, viral-free and feeder-free technique.
Primary Outcome Measure Information:
Title
Incidence and severity of treatment emergent adverse events [safety and tolerability]
Description
Safety
Time Frame
28 days
Title
Incidence and severity of serious adverse events deemed possibly related to CYP-001 [safety and tolerability]
Description
Safety
Time Frame
100 days
Secondary Outcome Measure Information:
Title
Complete Response by Day 28
Description
Proportion of participants who show a Complete Response (absence of any signs or symptoms of GvHD) by Day 28
Time Frame
28 days
Title
Partial Response by Day 28
Description
Proportion of participants who show a Partial Response (improvement in the severity of GvHD by at least one grade compared to baseline) by Day 28
Time Frame
28 days
Title
Overall Survival at Day 28
Description
Proportion of participants who survive until Day 28
Time Frame
28 days
Title
Complete Response by Day 100
Description
Proportion of participants who show a Complete Response by Day 100
Time Frame
100 days
Title
Partial Response by Day 100
Description
Proportion of participants who show a Partial Response by Day 100
Time Frame
100 days
Title
Overall Survival at Day 100
Description
Proportion of participants who survive until Day 100
Time Frame
100 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis using consensus grading with steroid-resistant Grade II-IV acute GvHD, after a haematopoietic stem cell transplant for a haematological disorder.
Life expectancy of at least one month.
Agree to have follow-up data collected for two years after their initial dose of CYP-001 (under a separate protocol).
Exclusion Criteria:
Pregnant or breastfeeding or plan to become pregnant within three months of receiving their last dose of CYP-001.
Have received any investigational research agent within 30 days or five half-lives (whichever is longer) prior to the first dose of IMP.
Known or suspected current alcohol or substance abuse problem.
Progressive or relapsing haematological malignancy, a current solid tumour, or previous malignant solid tumour that is likely to recur during the period of the study (with the exception of a past history of basal or squamous cell carcinomas).
Heart failure (NYHA Functional Class II-IV) and/or pulmonary failure.
Haemodynamically unstable and/or at high risk of cardiovascular events.
Terminal organ failure.
Meningitis, pneumonia with hypoxemia, HIV or another severe or uncontrolled systemic infection, which in the opinion of the investigator is likely to impact on the ability of the patient to participate in the trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kilian Kelly, PhD
Organizational Affiliation
Cynata Therapeutics Limited
Official's Role
Study Director
Facility Information:
Facility Name
Sydney Local Health District
City
Sydney
State/Province
New South Wales
Country
Australia
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
Country
Australia
Facility Name
NHS Foundation Trust
City
Bristol
Country
United Kingdom
Facility Name
NHS Trust
City
Leeds
Country
United Kingdom
Facility Name
NHS Foundation Trust
City
Liverpool
Country
United Kingdom
Facility Name
NHS Foundation Trust
City
Manchester
Country
United Kingdom
Facility Name
NHS Foundation Trust
City
Nottingham
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
32929265
Citation
Bloor AJC, Patel A, Griffin JE, Gilleece MH, Radia R, Yeung DT, Drier D, Larson LS, Uenishi GI, Hei D, Kelly K, Slukvin I, Rasko JEJ. 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. Nat Med. 2020 Nov;26(11):1720-1725. doi: 10.1038/s41591-020-1050-x. Epub 2020 Sep 14.
Results Reference
derived
Learn more about this trial
A Study of CYP-001 for the Treatment of Steroid-Resistant Acute Graft Versus Host Disease
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