A Study of CYP-001 in Combination With Corticosteroids in Adults With High-risk aGvHD

Phase 2Active Not RecruitingNCT05643638

Cynata Therapeutics Limited60 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Graft Versus Host Disease, Acute

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (39)

Banner MD Anderson

Phoenix, Arizona, United States

Mayo Clinic Hospital

Phoenix, Arizona, United States

University of Arkansas Medical Center

Little Rock, Arkansas, United States

Mayo Clinic Hospital

Jacksonville, Florida, United States

Memorial healthcare System

Pembroke Pines, Florida, United States

Outcomes

Primary Outcomes

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.

Time frame: 28 days

Secondary Outcomes

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

Time frame: 100 days

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.

Time frame: 100 days

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.

Time frame: 100 days

Overall survival

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

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 frame: 2 years

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.

Time frame: 2 years

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 frame: 2 years

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.

Time frame: 2 years

Incidence of chronic GvHD

Chronic GvHD is defined as the diagnosis of mild, moderate, or severe chronic GvHD.

Time frame: 2 years

Weekly cumulative steroid dose

The total corticosteroid dose administered each week

Time frame: 100 days

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.

Time frame: 2 years

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

Time frame: 2 years

Incidence, severity, duration of treatment-emergent adverse events

Assessment of safety

Time frame: 2 years