2025-523448-10-00招募中2 期
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
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia8 个研究点 分布在 1 个国家目标入组 26 人开始时间: 2026年5月1日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 26
- 试验地点
- 8
- 主要终点
- Overall response rate (ORR) on day 28, defined as the sum of complete and partial responses according to modified MAGIC/Glucksberg criteria.
研究概览
简要总结
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).
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •Known allergy to MSC product or its excipients (e.g., DMSO)
- •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
- •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).
研究组 & 干预措施
MC0518
Test
干预措施: MC0518 (Drug)
结局指标
主要结局
Overall response rate (ORR) on day 28, defined as the sum of complete and partial responses according to modified MAGIC/Glucksberg criteria.
Overall response rate (ORR) on day 28, defined as the sum of complete and partial responses according to modified MAGIC/Glucksberg criteria.
次要结局
- Duration of response
- ORR at day 56 and at 3 months
- Best overall response within 3 months
- Cumulative corticosteroid dose up to day 56 and at 3 months
- Overall survival (OS) and progression-free survival (PFS) at 6 and 12 months
- Non-relapse mortality (NRM) at 3, 6, and 12 months
- Incidence of chronic GvHD at 12 months
- Rate of corticosteroid discontinuation
- Impact on quality of life (EQ-5D) at end of treatment and during follow-up
- Safety profile up to 12 months, including incidence of serious adverse events, late infections, and product-related toxicities
研究者
Dr. Aldo M. Roccaro
Scientific
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
研究点 (8)
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