Efficacy of MC0518 Allogeneic Mesenchymal Stromal Cells in Adult Patients with Grade II–IV Acute Graft-Versus-Host Disease Refractory to Corticosteroids and Ruxolitinib

Trial ID: 2025-523448-10-00
Sponsor: Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia

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Diseases & Conditions

Graft versus host disease

Objectives

The primary objective is to evaluate the efficacy of allogeneic mesenchymal stromal cells (allo-MSCs) in adult patients presenting with grade II–IV acute graft-versus-host disease (aGvHD) that is refractory to both corticosteroid therapy and ruxolitinib. The secondary objectives include:

Assessment of sustained efficacy over time.
Evaluation of the impact on corticosteroid management.
Assessment of medium-term clinical outcomes.
Evaluation of quality of life.
Assessment of the safety of the MSC therapy.

Participants

The sponsor did not provide information regarding the total number of participants. The study population consists of adult patients, including both males and females, diagnosed with acute graft-versus-host disease. Eligible individuals must have undergone allogeneic hematopoietic stem cell transplantation for either malignant or non-malignant hematologic disease. Participants must present with grade II–IV acute graft-versus-host disease according to the MAGIC criteria that is refractory to corticosteroid therapy and subsequently resistant to ruxolitinib. Inclusion requires patients to be at least 18 years of age. Women of childbearing potential and men with partners of childbearing potential are required to utilize effective contraception methods for a specified duration.

Plans and Procedures

This Phase IIB clinical trial is designed to evaluate the efficacy of allogeneic mesenchymal stromal cells (allo-MSCs) in adult patients diagnosed with acute graft-versus-host disease that is refractory to both corticosteroids and ruxolitinib. The study involves the intravenous infusion of a dispersion for infusion containing 2,000,000 mesenchymal stromal cells, ex vivo cultured. The research methodology focuses on determining the overall response rate at day 28 as the primary endpoint, according to modified MAGIC/Glucksberg criteria. Secondary endpoints include the duration of response, overall survival, progression-free survival, and the safety profile through 12 months of follow-up. The trial sequence begins with a screening visit to confirm eligibility based on allogeneic hematopoietic stem cell transplantation history and disease grade. Following administration, participants undergo scheduled assessments to monitor cumulative corticosteroid doses, non-relapse mortality, and the incidence of chronic graft-versus-host disease. The overall duration of participant involvement and follow-up extends to at least 12 months to evaluate late infections and product-related toxicities.

Treatment

The experimental treatment consists of MC0518, which contains mesenchymal stromal cells that have been ex vivo cultured. This product is prepared as a dispersion for infusion. The administration involves an intravenous infusion of 2,000,000 cells.

Efficacy

The primary efficacy endpoint is the overall response rate (ORR) assessed on day 28, which is determined by the sum of complete and partial responses utilizing the modified MAGIC/Glucksberg criteria. Secondary endpoints include the ORR at day 56 and at 3 months, the best overall response within a 3-month period, and the duration of response.

Additional efficacy parameters include the cumulative corticosteroid dose up to day 56 and at 3 months, as well as the rate of corticosteroid discontinuation. Survival outcomes are evaluated through overall survival (OS) and progression-free survival (PFS) at 6 and 12 months. The non-relapse mortality (NRM) is monitored at 3, 6, and 12 months, and the incidence of chronic graft-versus-host disease is assessed at 12 months. The impact on quality of life is measured using the EQ-5D instrument at the end of treatment and during follow-up.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Age ≥18 years
Allogeneic HSCT performed for malignant or non-malignant hematologic disease
Diagnosis of grade II–IV acute GvHD according to MAGIC criteria
Patients resistant to steroids AND resistant Ruxolitinib meeting the following criteria: ‐ Refractoriness 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). ‐ Refractoriness 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.
Signed informed consent by the patient or legally authorized representative
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
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.
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.

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Exclusion Criteria

Known allergy to MSC product or its excipients (e.g., DMSO)
ECOG performance status ≥3
CD3+ chimerism <90%
Progression of the underlying hematologic disease
Previous treatment for aGvHD with agents other than corticosteroids and ruxolitinib
patients with chronic obstructive or severe restrictive pulmonary disease at time of transplant.
Participant receiving any other investigational agents (not approved by the EMA) concurrently during study participation or within 30 days of randomization
Participant receiving transplant for non haematological malignancies
Patients with overlap chronic GvHD (NIH Consensus Criteria).
Grade II-IV hyper-acute GvHD (defined as aGVHD between day 0 and day +14 after transplant).
Know hypersensitivity to MC0518 and / or its excipients (eg, dimethyl sulfoxide)
Previous treatment with mesenchymal stromal cells (MSCs) for acute GvHD.
Pregnant or breastfeeding women.
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.
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.
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.
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