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A Study of CYP-001 for the Treatment of Steroid-Resistant Acute Graft Versus Host Disease

Phase 1
Completed
Conditions
Graft vs Host Disease
Interventions
Biological: Mesenchymoangioblast-derived mesenchymal stem cells
Registration Number
NCT02923375
Lead Sponsor
Cynata Therapeutics Limited
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
16
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Cohort AMesenchymoangioblast-derived mesenchymal stem cellsMesenchymoangioblast-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)
Cohort BMesenchymoangioblast-derived mesenchymal stem cellsMesenchymoangioblast-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)
Primary Outcome Measures
NameTimeMethod
Incidence and severity of treatment emergent adverse events [safety and tolerability]28 days

Safety

Incidence and severity of serious adverse events deemed possibly related to CYP-001 [safety and tolerability]100 days

Safety

Secondary Outcome Measures
NameTimeMethod
Overall Survival at Day 2828 days

Proportion of participants who survive until Day 28

Partial Response by Day 100100 days

Proportion of participants who show a Partial Response by Day 100

Complete Response by Day 2828 days

Proportion of participants who show a Complete Response (absence of any signs or symptoms of GvHD) by Day 28

Partial Response by Day 2828 days

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

Complete Response by Day 100100 days

Proportion of participants who show a Complete Response by Day 100

Overall Survival at Day 100100 days

Proportion of participants who survive until Day 100

Trial Locations

Locations (4)

NHS Foundation Trust

🇬🇧

Nottingham, United Kingdom

NHS Trust

🇬🇧

Leeds, United Kingdom

Sydney Local Health District

🇦🇺

Sydney, New South Wales, Australia

Royal Adelaide Hospital

🇦🇺

Adelaide, South Australia, Australia

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