Clinical trial NCT05643638: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Graft Versus Host Disease, Acute
Lead sponsor: Cynata Therapeutics Limited
Sponsor class: INDUSTRY
First posted: 2022-12-09
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: 28 days
Secondary outcomes:
measure: Durable Overall response rate (ORR)
timeFrame: 100 days
measure: Overall response rate (ORR)
timeFrame: 100 days
measure: Complete response rate (CRR)
timeFrame: 100 days
measure: Overall survival
timeFrame: 2 years
measure: Event-free survival
timeFrame: 2 years
measure: Time to non-relapse mortality
timeFrame: 2 years
measure: Failure-free survival
timeFrame: 2 years
measure: Time to malignancy relapse/progression
timeFrame: 2 years
measure: Incidence of chronic GvHD
timeFrame: 2 years
measure: Weekly cumulative steroid dose
timeFrame: 100 days
measure: Patient reported outcomes: Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) instrument
timeFrame: 2 years
measure: Patient reported outcomes: EuroQol 5-Dimension (EQ-5D) health-related quality of life instrument
timeFrame: 2 years
measure: Incidence, severity, duration of treatment-emergent adverse events
timeFrame: 2 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner MD Anderson
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas Medical Center
state: Arkansas
city: Jacksonville
country: United States
facility: Mayo Clinic Hospital
state: Florida
city: Pembroke Pines
country: United States
facility: Memorial healthcare System
state: Florida
city: Atlanta
country: United States
facility: BMT Group of Georgia
state: Georgia
city: Evanston
country: United States
facility: Northwestern University
state: Illinois
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Omaha
country: United States
facility: University Of Nebrasaka Medical Center
state: Nebraska
city: New York
country: United States
facility: Weill Cornell Medicine - New York Presbyterian Hospital
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Hershey
country: United States
facility: Penn State Health
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Sydney
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Lille
country: France
facility: Hospital Claude Huriez
city: Paris
country: France
facility: Hôpital Necker Enfants Malades
city: Paris
country: France
facility: Hôpital Universitaire Pitié-Salpêtrière
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria delle Marche
city: Milan
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Ospedale Casa Sollievo della Sofferenza
city: Venezia
country: Italy
facility: Ospedale dell'Angelo di Mestre
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santaros Klinikos
city: Barcelona
country: Spain
facility: ICO l'Hospitalet - Hospital Duran i Reynals
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitato De La Princesa
city: Murcia
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
city: Eskişehir
country: Turkey
facility: Anadolu Medical Center
city: Istanbul
country: Turkey
facility: Gayrettepe Florence Nightingale Hastanesi
city: Istanbul
country: Turkey
facility: Koc University
city: Istanbul
country: Turkey
facility: Memorial Bahcelievler Hospital
city: Izmir
country: Turkey
facility: Izmir Medicalpark Hospital
city: Malatya
country: Turkey
facility: İnonu University
city: Yenimahalle
country: Turkey
facility: Dr Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi
Study officials:
affiliation: Cynata Therapeutics Limited
name: Jolanta Airey, MD
role: STUDY_DIRECTOR
References: