Mesenchymal stromal cells, ex vivo cultured for Acute graft-versus-host disease (aGvHD) refractory to ruxolitinib and corticosteroids

Inclusion criteria

• {"criterion_text":"- Age ≥18 years"}
• {"criterion_text":"- Allogeneic HSCT performed for malignant or non-malignant hematologic disease"}
• {"criterion_text":"- Diagnosis of grade II–IV acute GvHD according to MAGIC criteria"}
• {"criterion_text":"- Patients resistant to steroids AND resistant Ruxolitinib meeting the following criteria: ‐\tRefractoriness to corticosteroids is defined as at least one of the following: (1) progression of aGvHD after at least 3 days of treatment with systemic corticosteroids at a dose equivalent to ≥2 mg/kg/day of methylprednisolone (or equivalent); (2) lack of response after at least 7 days of treatment with systemic corticosteroids at a dose equivalent to ≥2 mg/kg/day of methylprednisolone (or equivalent);(3) for patients with isolated upper gastrointestinal or skin involvement, lack of response after at least 7 days of treatment with methylprednisolone at a dose of ≥1 mg/kg/day (or equivalent). ‐\tRefractoriness to ruxolitinib is defined as at least one of the following: (1) progression of GVHD compared with baseline after at least 7 days of treatment with Ruxolitinib 5 mg BD or 10 mg BD, based either on objective increase in stage/grade, or new organ involvement; (2) lack of improvement in GVHD (partial response or better) compared with baseline after ≥14 days of treatment with Ruxolitinib; or (3) loss of response, defined as objective worsening of GVHD determined by increase in stage, grade, or new organ involvement at any time after initial improvement. GVHD manifestations that persist without any improvement in patients who present with grade III or higher aGVHD at baseline.Moreover, failure to achieve a complete or partial response by Day 28 of Ruxolitinib therapy is as an additional eligibility criterion."}
• {"criterion_text":"- Signed informed consent by the patient or legally authorized representative"}
• {"criterion_text":"- Willingness and ability of the subject to comply with study procedures, treatment administration, and scheduled follow-up assessments, as specified in the protocol, in the opinion of the Investigator"}
• {"criterion_text":"- For women of childbearing potential: use of highly effective contraception methods, as defined by applicable guidelines, from study entry and for at least 90 days after the last administration of the investigational product."}
• {"criterion_text":"- For male participants with partners of childbearing potential: agreement to use effective contraception during the study and for at least 90 days after the last administration of the investigational product."}

Exclusion criteria

• {"criterion_text":"- Known allergy to MSC product or its excipients (e.g., DMSO)"}
• {"criterion_text":"- Grade II-IV hyper-acute GvHD (defined as aGVHD between day 0 and day +14 after transplant)."}
• {"criterion_text":"- Know hypersensitivity to MC0518 and / or its excipients (eg, dimethyl sulfoxide)"}
• {"criterion_text":"- Previous treatment with mesenchymal stromal cells (MSCs) for acute GvHD."}
• {"criterion_text":"- Pregnant or breastfeeding women."}
• {"criterion_text":"- Women of childbearing potential not willing to use highly effective contraception during the study and for at least 90 days after the last administration of the investigational product."}
• {"criterion_text":"- Male participants with partners of childbearing potential who are not willing to use effective contraception during the study and for at least 90 days after the last administration of the investigational product."}
• {"criterion_text":"- Patients with severe, uncontrolled, or end-stage organ dysfunction, including cardiac, hepatic, renal, or respiratory impairment, which in the opinion of the Investigator would significantly limit life expectancy, coromise the subject’s ability to tolerate MC0518 administration or study procedures, or interfere with the assessment of study endpoints. Subjects with rapidly progressive clinical deterioration or a life-threatening condition not primarily attributable to acute GvHD, and likely to result in death in the short term, should not be enrolled. This may include, but is not limited to, severe cardiovascular disease, uncontrolled metabolic disorders, active malimpgnancies other than the underlying hematologic disease, or other clinically significant conditions."}
• {"criterion_text":"- Patients with HBV, HCV, or HIV infection associated with uncontrolled viral replication, absence of appropriate specialist follow-up, or clinical conditions that, in the opinion of the Investigator, may compromise subject safety or interfere with study participation"}
• {"criterion_text":"- ECOG performance status ≥3"}
• {"criterion_text":"- CD3+ chimerism <90%"}
• {"criterion_text":"- Progression of the underlying hematologic disease"}
• {"criterion_text":"- Previous treatment for aGvHD with agents other than corticosteroids and ruxolitinib"}
• {"criterion_text":"- patients with chronic obstructive or severe restrictive pulmonary disease at time of transplant."}
• {"criterion_text":"- Participant receiving any other investigational agents (not approved by the EMA) concurrently during study participation or within 30 days of randomization"}
• {"criterion_text":"- Participant receiving transplant for non haematological malignancies"}
• {"criterion_text":"- Patients with overlap chronic GvHD (NIH Consensus Criteria)."}

Primary endpoints

• {"endpoint_text":"- Overall response rate (ORR) on day 28, defined as the sum of complete and partial responses according to modified MAGIC/Glucksberg criteria.","definition_or_measurement_approach":"ORR measured on Day 28 as the sum of complete and partial responses assessed using modified MAGIC/Glucksberg criteria."}

Secondary endpoints

• {"endpoint_text":"- ORR at day 56 and at 3 months","definition_or_measurement_approach":"ORR measured at Day 56 and at 3 months using response criteria (as per protocol)."}
• {"endpoint_text":"- Best overall response within 3 months","definition_or_measurement_approach":"Best recorded response within the 3-month assessment window."}
• {"endpoint_text":"- Duration of response","definition_or_measurement_approach":"Time from documented response until relapse or progression (protocol-defined)."}
• {"endpoint_text":"- Cumulative corticosteroid dose up to day 56 and at 3 months","definition_or_measurement_approach":"Cumulative corticosteroid exposure calculated up to Day 56 and at 3 months."}
• {"endpoint_text":"- Overall survival (OS) and progression-free survival (PFS) at 6 and 12 months","definition_or_measurement_approach":"OS and PFS measured at 6 and 12 months per standard definitions (time-to-event analyses)."}
• {"endpoint_text":"- Non-relapse mortality (NRM) at 3, 6, and 12 months","definition_or_measurement_approach":"NRM assessed at 3, 6, and 12 months (deaths not due to relapse)."}
• {"endpoint_text":"- Incidence of chronic GvHD at 12 months","definition_or_measurement_approach":"Incidence measured at 12 months using NIH Consensus Criteria for chronic GvHD."}
• {"endpoint_text":"- Rate of corticosteroid discontinuation","definition_or_measurement_approach":"Proportion of patients discontinuing corticosteroids during follow-up as recorded in study data."}
• {"endpoint_text":"- Impact on quality of life (EQ-5D) at end of treatment and during follow-up","definition_or_measurement_approach":"Quality of life assessed with EQ-5D at end of treatment and during follow-up visits."}
• {"endpoint_text":"- Safety profile up to 12 months, including incidence of serious adverse events, late infections, and product-related toxicities","definition_or_measurement_approach":"Safety assessed through reporting of adverse events, serious adverse events, infections, and product-related toxicities up to 12 months."}

Italy

Earliest CTIS Part Ii Submission Date

30-03-2026

Latest Decision Or Authorization Date

28-04-2026

Processing Time Days

29

Number Of Sites

8

Number Of Participants

26

Primary sponsor

Full Name

Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy