Clinical trial NCT02923375: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Graft vs Host Disease
Lead sponsor: Cynata Therapeutics Limited
Sponsor class: INDUSTRY
First posted: 2016-10-04
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Incidence and severity of treatment emergent adverse events [safety and tolerability]
timeFrame: 28 days
measure: Incidence and severity of serious adverse events deemed possibly related to CYP-001 [safety and tolerability]
timeFrame: 100 days
Secondary outcomes:
measure: Complete Response by Day 28
timeFrame: 28 days
measure: Partial Response by Day 28
timeFrame: 28 days
measure: Overall Survival at Day 28
timeFrame: 28 days
measure: Complete Response by Day 100
timeFrame: 100 days
measure: Partial Response by Day 100
timeFrame: 100 days
measure: Overall Survival at Day 100
timeFrame: 100 days
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Sydney Local Health District
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Bristol
country: United Kingdom
facility: NHS Foundation Trust
city: Leeds
country: United Kingdom
facility: NHS Trust
city: Liverpool
country: United Kingdom
facility: NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: NHS Foundation Trust
Study officials:
affiliation: Cynata Therapeutics Limited
name: Kilian Kelly, PhD
role: STUDY_DIRECTOR
References:
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.