Phase I/IIa Study of Allogeneic Adipose-Derived Mesenchymal Stromal Cells Ectopically Expressing CXCR4 and IL-10 in Patients with Steroid- or Ruxolitinib-Refractory Acute GVHD
- Trial ID
- 2025-523139-21-00
- Protocol
- 2G-MSC-GVHD
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the safety and tolerability of administering allogeneic adipose tissue-derived mesenchymal stromal cells genetically modified to ectopically express CXCR4 and IL-10. This investigation is conducted in patients diagnosed with acute graft versus host disease who are refractory to corticosteroids and ruxolitinib or are ineligible for ruxolitinib therapy.
Participants
The sponsor did not provide the total number of participants. The study population consists of male and female patients between 18 and 75 years of age who have undergone allogeneic hematopoietic stem cell transplantation. Eligible individuals must have a clinical diagnosis of acute graft-versus-host disease, specifically grades II to IV, occurring after transplantation. The cohort is composed of patients with disease that is refractory to corticosteroids and ruxolitinib or those who are ineligible for ruxolitinib therapy due to conditions such as severe thrombocytopenia or neutropenia. Participants must meet specific criteria regarding steroid-refractory status or disease progression during ruxolitinib treatment.
Plans and Procedures
This Phase I/IIa clinical trial is designed to evaluate the safety and tolerability of allogeneic adipose tissue-derived mesenchymal stromal cells genetically modified to ectopically express CXCR4 and IL10. The study focuses on patients with acute graft versus host disease that is refractory to corticosteroids and ruxolitinib, or those ineligible for ruxolitinib treatment. The therapeutic product is administered via intravenous infusion as a cell suspension for injection. The research methodology involves a screening visit to confirm eligibility based on clinical diagnosis, age, and previous allogeneic hematopoietic stem cell transplantation status. Following screening, participants will undergo sequential infusions of the investigational product. The study includes follow-up visits to monitor for serious adverse reactions and to assess efficacy through clinical and biological parameters. The total duration of the study is estimated to span from January 2026 to January 2028. Participant involvement includes the initial screening, the treatment period, and subsequent monitoring until the end-of-study visit. Early termination from the study may occur based on investigator criteria or clinical necessity.
Treatment
The experimental treatment consists of allogeneic adipocyte-derived mesenchymal stromal cells transduced with a lentiviral provirus vector containing the human CXCR4 and IL-10 genes. This therapeutic agent is administered as a cell suspension for injection via intravenous infusion for the treatment of graft versus host disease.
Efficacy
Efficacy will be evaluated through the analysis of clinical parameters and biological parameters in patients diagnosed with acute graft versus host disease. The assessment is designed to determine the therapeutic response following the administration of allogeneic adipose tissue-derived mesenchymal stromal cells ectopically expressing CXCR4 and IL-10.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Have undergone alloHSCT from any donor source (matched unrelated donor, sibling, haploidentical) using bone marrow, peripheral blood stem cells, or cord blood
- Recipients of nonmyeloablative, myeloablative, and reduced intensity conditioning are eligible.
- Male or female subjects between 18 and 75 years of age.
- Clinically diagnosed grades II to IV acute GVHD as per standard criteria (Annex 2) occurring after alloHSCT. Biopsy of involved organs with aGVHD is encouraged but not required for study screening
- Confirmed diagnosis of steroid AND ruxolitinib relapse or refractory aGVHD or non-eligible to ruxolitinib, defined as: a) Progression of GVHD compared with baseline after at least 7 days of treatment with ruxolitinib, based either on objective increase in stage/grade, or new organ involvement. b) Lack of improvement in GVHD (partial response or better) compared with baseline after at least 14 days of treatment with ruxolitinib c) Loss of response to ruxolitinib, 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 improvement in patients who had a grade ≥3 treatment-emergent and ruxolitinib-attributed adverse event that did not resolve within 7 days of discontinuing ruxolitinib would serve as a clinical indication for additional treatment. Patients considered non-eligible to ruxolitinib should be steroid refractory, defined as: progression of GVHD compared with baseline after 3 days of corticosteroid treatment, a lack of response after 7 days or treatment failure during glucocorticoid taper. For these patients, inclusion criteria might be: d) Severe thrombocytopenia < 20000/mm3 or neutropenia < 500/mm3 e) Any other clinical condition that makes the patient non eligible to ruxolitinib treatment at the investigator criteria
- Female subjects who are: Postmenopausal for at least 1 year before signing of the informed consent, OR surgically sterile OR if they are aged 18 years or greater and not postmenopausal or surgically sterilized must use a highly effective method of contraception during the study, OR agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject.
Exclusion Criteria
- Hematological disease not controlled by the transplant or in progression at the time of inclusion.
- Positive PCR for SARS COV2 within 10 days prior to mesenchymal cells infusion
- If female, the subject is pregnant, lactating or breastfeeding, or intending to become pregnant before, during, or within 18 weeks after participating in this study, or intending to donate ova during such time period
- Any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, GI, genitourinary, coagulation, immunological, endocrine/metabolic, neurologic, or other medical disorder not related to the subject's primary disease that, in the opinion of the investigator, would confound the study results or compromise subject safety.
- Clinically active systemic infection during screening
- Patients who are currently participating or have completed their participation in a clinical trial in a period of less than 3 months
- Patients who have participated in an advanced therapies clinical trial (cell therapy, gene therapy or tissue engineering) at any previous time.
- Chronic hepatitis B (hepatitis B surface antigen [HBsAg] positive) or hepatitis C infection (evident by active viral replication by polymerase chain reaction [PCR] if hepatitis C virus antibody positive). Hepatitis B core antibody (HBcAb) positive (HBcAb+) and negative for hepatitis B surface antigen (HBsAg-) may be enrolled if viral DNA is undetectable
- History of human immunodeficiency virus (HIV) positive test
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Not Yet Recruiting | 05 Jan 2026 | 15 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Allogeneic Adipose Tissue Derived Mesenchymal Stromal Cells (MSC) ectopically expressing CXCR4 and IL10 | Test | CELL SUSPENSION FOR INJECTION | INFUSIÓN INTRAVENOSA | — | — | PRD12983852 |