Allogeneic mesenchymoangioblast-derived mesenchymal stem cells for Acute graft-versus-host disease (high-risk)

Inclusion criteria

• {"criterion_text":"- Male or female subjects 18 years of age or older\n- Provide written informed consent form and agree to comply with study procedures\n- 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\n- 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\n- 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\n- Evidence of myeloid engraftment post allogeneic HSCT defined as three (3) consecutive days of achieving sustained ANC >500 x 10^6/L. Use of G-CSF and blood transfusion is allowed.\n- Life expectancy of at least one month, in the opinion of the investigator.\n- 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

• {"criterion_text":"- 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.\n- Known sensitivity to dimethylsulfoxide (DMSO) or any other component of CYP-001.\n- Known or suspected current alcohol or substance abuse problem, in the opinion of the investigator.\n- Received any investigational treatment agent within 30 days or within 5 half-lives of Screening, whichever is greater.\n- 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. 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.\n- Pregnant, breastfeeding or not willing to cease breastfeeding.\n- Currently receiving a therapy not permitted during the study.\n- 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).\n- Clinical presentation of chronic GvHD or overlap syndrome with both acute and chronic features of GvHD\n- Presence of relapsed primary malignancy since allogeneic HSCT\n- Have received more than one allogeneic HSCT\n- Clinically significant respiratory, renal or cardiac disease at screening including any of the following: a. requiring mechanical ventilation or having resting SO2 <90% on pulse oximetry b. serum creatinine >2mg/dL or eGFR <30ml/min (Cockroft Gault equation) c. uncontrolled hypertension d. Congestive heart failure New York Heart Association Class III or IV\n- Presence of cholestatic disorders or sinusoidal obstructive syndrome/veno-occlusive disease of the liver defined as persistent bilirubin abnormalities not attributable to aGvHD\n- 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.\n- Known infection with CMV, EBV, HBV, HCV, HIV or Tuberculosis. If the treatment for CMV, EBV, HBV, HCV has commenced the subject is eligible for study.\n- 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."}

Primary endpoints

• {"endpoint_text":"- Overall Response Rate at Day 28 is defined as the proportion of participants in each treatment arm demonstrating a complete response (CR; resolution of aGvHD signs and symptoms) or a partial response (PR; an improvement in the severity of GvHD by at least one grade compared to baseline) without requirement for additional systemic therapies for an earlier progression, a mixed response or a lack of response.","definition_or_measurement_approach":"Overall Response Rate at Day 28: proportion of participants in each arm with CR (resolution of aGvHD signs and symptoms) or PR (improvement in severity by ≥1 grade vs baseline) without requirement for additional systemic therapies for earlier progression, mixed response, or lack of response."}

Secondary endpoints

• {"endpoint_text":"- Proportion of all subjects in each treatment arm with durable overall response (OR) defined as patients with OR (CR or PR) at Day 28 and maintain an OR at Day 60 and Day 100; Proportion of all subjects in each treatment arm with OR defined as subjects with complete response (CR) or partial response (PR) at Day 7, Day 14, Day 21, Day 60 and Day 100; Proportion of all subjects in each treatment arm with CR at Day 28, Day 60 and Day 100","definition_or_measurement_approach":"Durable OR: patients with CR or PR at Day 28 who maintain CR/PR at Day 60 and Day 100. Also proportions with CR/PR at Days 7, 14, 21, 60, 100 and CR at Days 28, 60, 100."}
• {"endpoint_text":"- Overall Survival (OS) is defined as the time from date of randomization to the date of death due to any cause","definition_or_measurement_approach":"OS: time from randomization to death from any cause."}
• {"endpoint_text":"- Event-Free survival (EFS) is defined as the time from the date of randomization (baseline) to the date of hematologic disease relapse/progression, graft failure, or death due to any cause.","definition_or_measurement_approach":"EFS: time from randomization to hematologic disease relapse/progression, graft failure, or death."}
• {"endpoint_text":"- Time to Non-Relapse Mortality (NRM) is defined as the time from the date of randomization (baseline) to the date of death not preceded by hematologic disease relapse/progression.","definition_or_measurement_approach":"Time to NRM: time from randomization to death not preceded by hematologic disease relapse/progression."}
• {"endpoint_text":"- Failure Free Survival (FFS) is defined as the time from the date of randomization (baseline) to date of hematologic disease relapse/progression, non-relapse mortality, or addition of new systemic aGvHD treatment; Hematologic disease Relapse/Progression is defined as the time from the date of randomization (baseline) to the date to hematologic disease (malignant or non-malignant) relapse/progression.","definition_or_measurement_approach":"FFS: time from randomization to hematologic disease relapse/progression, non-relapse mortality, or addition of new systemic aGvHD treatment."}
• {"endpoint_text":"- cGvHD is defined as the diagnosis of mild, moderate, or severe cGvHD","definition_or_measurement_approach":"cGvHD incidence: diagnosis categorized as mild, moderate, or severe chronic GvHD."}
• {"endpoint_text":"- Weekly cumulative steroid dose for each subject up to Day 100 or end of treatment will be calculated","definition_or_measurement_approach":"Cumulative steroid dose: weekly cumulative steroid dose calculated for each subject up to Day 100 or end of treatment."}
• {"endpoint_text":"- Changes in Patient Reported Outcomes (PRO)","definition_or_measurement_approach":"PROs: changes from baseline in subject-reported outcome measures (instruments specified in protocol)."}
• {"endpoint_text":"- To evaluate the incidence, severity, duration of TEAE, changes from baseline in hematology, biochemistry, coagulation profile","definition_or_measurement_approach":"Safety: incidence, severity, duration of treatment-emergent adverse events (TEAEs); laboratory changes from baseline in hematology, biochemistry and coagulation parameters."}

Spain

Earliest CTIS Part Ii Submission Date

17-01-2024

Latest Decision Or Authorization Date

11-03-2024

Processing Time Days

54

Number Of Sites

6

Number Of Participants

12

Lithuania

Earliest CTIS Part Ii Submission Date

02-02-2024

Latest Decision Or Authorization Date

10-01-2025

Processing Time Days

343

Number Of Sites

1

Number Of Participants

5

Italy

Earliest CTIS Part Ii Submission Date

12-02-2024

Latest Decision Or Authorization Date

23-05-2025

Processing Time Days

466

Number Of Sites

6

Number Of Participants

12

France

Earliest CTIS Part Ii Submission Date

24-01-2024

Latest Decision Or Authorization Date

04-02-2026

Processing Time Days

742

Number Of Sites

4

Number Of Participants

9

Primary sponsor

Full Name

Cynata Therapeutics Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

Australia

Contract research organisations

Name

Iqvia Biotech Limited

Responsibilities

Application correspondent on behalf of sponsor and multiple clinical operations/support responsibilities (as listed in sponsor duties)

Name

PureCDM Pty Ltd

Responsibilities

Trainings

Name

Quanticate UK Limited

Responsibilities

Pharmacovigiliance

Name

Labcorp Central Laboratory Services S.a.r.l. Meyrin

Responsibilities

Kit and supply shipping

Third parties

• {"country":"United Kingdom","full_name":"Quanticate UK Limited","duties_or_roles":"Pharmacovigiliance","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Millmount Healthcare Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Australia","full_name":"PureCDM Pty Ltd","duties_or_roles":"Trainings","organisation_type":"Industry"}
• {"country":"United Kingdom","full_name":"Iqvia Biotech Limited","duties_or_roles":"Multiple roles including application correspondent on behalf of sponsor and other study support functions (as listed in sponsor duties)","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services S.a.r.l. Meyrin","duties_or_roles":"Kit and supply shipping","organisation_type":"Pharmaceutical company"}