IRB Study Number 24-658
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objective
To assess efficacy of CYP-001 in subjects with HR-aGvHD by Overall Response Rate (ORR) at Day 28.
Secondary Objectives
To assess additional responses and long-term efficacy outcomes
To assess Overall Survival (OS)
To assess Event-Free survival (EFS)
To assess Non-Relapse Mortality (NRM)
To assess Failure Free Survival
To assess the incidence of relapse/progression of the underlying hematologic disease for which allogeneic HSCT was performed
To measure the incidence of chronic GvHD
To assess the cumulative steroid dose until Day 100
To evaluate changes in Subject Reported Outcomes
To evaluate the safety and tolerability of CYP-001 in subjects with HR-aGvHD
Inclusion Criteria
Male or female subjects 18 years of age or older.
Provide written informed consent form and agree to comply with study procedures.
Have undergone first allogeneic hematopoietic stem cell transplant (HSCT), to treat a hematologic disease (malignant or non-malignant), from any donor source (matched and mismatched) using bone marrow, peripheral blood stem cells, or cord blood and any conditioning intensity.
Have been clinically diagnosed with acute GvHD requiring systemic therapy with CS. Patients can be enrolled with only a clinically established diagnosis. Biopsy of involved organs with acute GvHD is encouraged but is not required and should not delay study entry. Enrollment/randomization includes commitment to continue steroids.
HR-aGvHD must meet one of the following clinical features within 72 hours prior to randomization:
A. High-risk as per Refined Minnesota Criteria:
• Single organ involvement
O Stage 4 skin
O Stage 3-4 lower GI
O Stage 1-4 liver
• Multiple organ involvement
O Stage 1-2 lower GI plus any liver
O Stage 2 lower GI plus any skin
O Stage 3-4 lower GI plus any liver or skin
O Any three organ involvement OR
B. One of the following:
• Isolated stage 2 involvement of the lower GI tract
• Stage 1 lower GI tract disease with skin involvement
Evidence of myeloid engraftment post allogeneic HSCT defined as three (3) consecutive days of achieving sustained ANC >500 x 106/L. Use of G-CSF and blood transfusion is allowed.
Life expectancy of at least one month, in the opinion of the investigator.
Investigator believes that the subject (or the subject’s legally acceptable representative[s]) understands the nature, scope and possible consequences of the study.
Exclusion Criteria
Has received any systemic treatment for aGvHD other than corticosteroids +/- CNI (prophylaxis or treatment). Treatment with CS is allowed for up to 72 hours prior to Day 0.
Clinical presentation of chronic GvHD or overlap syndrome with both acute and chronic features of GvHD
Presence of relapsed primary malignancy since allogeneic HSCT
Have received more than one allogeneic HSCT
Clinically significant respiratory, renal or cardiac disease at screening including any of the following:
(e) requiring mechanical ventilation or having resting SO2 <90% on pulse oximetry
(f) serum creatinine >2mg/dL or eGFR <30ml/min (Cockroft Gault equation)
(g) uncontrolled hypertension
(h) Congestive heart failure New York Heart Association Class III or IV
Presence of cholestatic disorders or sinusoidal obstructive syndrome/veno-occlusive disease of the liver defined as persistent bilirubin abnormalities not attributable to aGvHD
Presence of any active uncontrolled infection requiring treatment and which in the opinion of the Investigator and/or Study medical monitor is likely to impact on the ability of the subject to participate in the trial. Infections are considered controlled if appropriate therapy has been used and, at the time of screening, no signs of progression are present.
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 for study.
Any other medical or psychiatric condition which, in the opinion of the Investigator and/or Study medical monitor, makes the subject unsuitable for participation in the study or interfere with interpretation of study data.
Known sensitivity to dimethylsulfoxide (DMSO) or any other component of CYP-001.
Known or suspected current alcohol or substance abuse problem, in the opinion of the investigator.
Received any investigational treatment agent within 30 days or within 5 half-lives of Screening, whichever is greater.
Female subject of childbearing potential either not using or not willing to use an acceptable method of contraception to avoid pregnancy during the study and for 6 months after receipt of the last dose of investigational product. Acceptable methods of contraception are defined in Section 7.4.
All female subjects are assumed to be of childbearing potential except:
• Subjects aged > 60 years and postmenopausal.
• Subjects aged 45 to 60 years (inclusive) with amenorrhea for ≥ 1 year with documented evidence of follicle-stimulating hormone level > 30 IU/L. If the follicle-stimulating hormone value is not available before randomization, a urine pregnancy test is required.
• Subjects who are surgically sterile for at least 3 months before providing informed consent.
Pregnant, breastfeeding or not willing to cease breastfeeding.
Currently receiving a therapy not permitted during the study, as defined in Section 7.3.
Involved in the planning and / or conduct of the study (applies to Cynata Therapeutics Limited staff, staff at the study site, and third-party vendors).
