Efficacy of cell therapy with allo-MSCs in patients with gvhd resistant to ruxolitinib second line therapy: a Phase IIB Clinical Trial - MSC-GRR2 Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Decision date (initial)

2026-04-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To evaluate the efficacy of cell therapy with allogeneic mesenchymal stromal cells (allo-MSCs, MC0518) in adult patients with grade II–IV acute graft- versus-host disease (aGvHD) refractory to corticosteroid therapy and subsequently also to ruxolitinib treatment (RR-aGvHD).

Secondary objectives 5

1. To assess the sustained efficacy of MSC therapy over time
2. To evaluate the impact of MSC therapy on corticosteroid management
3. To assess medium-term clinical outcomes
4. To evaluate the impact on patient quality of life
5. To assess the safety of MSC therapy

Conditions and MedDRA coding

Gvhd Resistant to ruxolitinib and steroids

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Age ≥18 years
2. Allogeneic HSCT performed for malignant or non-malignant hematologic disease
3. Diagnosis of grade II–IV acute GvHD according to MAGIC criteria
4. 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.
5. Signed informed consent by the patient or legally authorized representative
6. 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
7. 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.
8. 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 17

1. Known allergy to MSC product or its excipients (e.g., DMSO)
2. ECOG performance status ≥3
3. CD3+ chimerism <90%
4. Progression of the underlying hematologic disease
5. Previous treatment for aGvHD with agents other than corticosteroids and ruxolitinib
6. patients with chronic obstructive or severe restrictive pulmonary disease at time of transplant.
7. Participant receiving any other investigational agents (not approved by the EMA) concurrently during study participation or within 30 days of randomization
8. Participant receiving transplant for non haematological malignancies
9. Patients with overlap chronic GvHD (NIH Consensus Criteria).
10. Grade II-IV hyper-acute GvHD (defined as aGVHD between day 0 and day +14 after transplant).
11. Know hypersensitivity to MC0518 and / or its excipients (eg, dimethyl sulfoxide)
12. Previous treatment with mesenchymal stromal cells (MSCs) for acute GvHD.
13. Pregnant or breastfeeding women.
14. 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.
15. 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.
16. 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.
17. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall response rate (ORR) on day 28, defined as the sum of complete and partial responses according to modified MAGIC/Glucksberg criteria.

Secondary endpoints 10

1. ORR at day 56 and at 3 months
2. Best overall response within 3 months
3. Duration of response
4. Cumulative corticosteroid dose up to day 56 and at 3 months
5. Overall survival (OS) and progression-free survival (PFS) at 6 and 12 months
6. Non-relapse mortality (NRM) at 3, 6, and 12 months
7. Incidence of chronic GvHD at 12 months
8. Rate of corticosteroid discontinuation
9. Impact on quality of life (EQ-5D) at end of treatment and during follow-up
10. Safety profile up to 12 months, including incidence of serious adverse events, late infections, and product-related toxicities

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia

Sponsor organisation

Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia

Address

Piazzale Spedali Civili 1

City

Brescia

Postcode

25123

Country

Italy

Scientific contact point

Organisation

Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia

Contact name

Dr. Aldo M. Roccaro

Public contact point

Organisation

Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia

Contact name

Dr. Aldo M. Roccaro

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications