Phase I/IIa Clinical Trial for the Treatment of Graft Versus Host Disease with a New Generation of Mesenchymal Stromal Cells Ectopically Expressing CXCR4 and IL-10 in Steroid-Refractory and Intolerant or Ruxolitinib-Refractory Patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Instituto De Investigacion Sanitaria De Navarra

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2026-04-09

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

To analyze the safety and tolerability of the administration of allogeneic adipose tissue MSCs genetically modified to ectopically express CXCR4 and IL10 for the treatment of patients who have developed acute GVHD refractory to corticosteroids and ruxolitinib or that are not eligible to receive ruxolitinib

Conditions and MedDRA coding

Patients who have developed acute GVHD refractory to corticosteroids and ruxolitinib or that are not eligible to receive ruxolitinib

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Have undergone alloHSCT from any donor source (matched unrelated donor, sibling, haploidentical) using bone marrow, peripheral blood stem cells, or cord blood
2. Recipients of nonmyeloablative, myeloablative, and reduced intensity conditioning are eligible.
3. Male or female subjects between 18 and 75 years of age.
4. 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
5. 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
6. 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 9

1. Hematological disease not controlled by the transplant or in progression at the time of inclusion.
2. Positive PCR for SARS COV2 within 10 days prior to mesenchymal cells infusion
3. 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
4. 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.
5. Clinically active systemic infection during screening
6. Patients who are currently participating or have completed their participation in a clinical trial in a period of less than 3 months
7. Patients who have participated in an advanced therapies clinical trial (cell therapy, gene therapy or tissue engineering) at any previous time.
8. 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
9. History of human immunodeficiency virus (HIV) positive test

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety: • Serious Adverse Reactions after sequential infusions of the study drug, regardless of the number of doses the patient has received and during the entire follow-up period. • Serious Unexpected Serious Adverse Reactions at the time of infusion or during follow-up

Secondary endpoints 1

1. Efficacy The response will be analyzed through clinical and biological parameters

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Instituto De Investigacion Sanitaria De Navarra

Sponsor organisation

Fundacion Instituto De Investigacion Sanitaria De Navarra

Address

Irunlarrea Kalea 3

City

Pamplona

Postcode

31008

Country

Spain

Scientific contact point

Organisation

Fundacion Instituto De Investigacion Sanitaria De Navarra

Contact name

Sara Villar Fernández

Public contact point

Organisation

Fundacion Instituto De Investigacion Sanitaria De Navarra

Contact name

Sara Villar Fernández

Third parties 1

Locations

1 EU/EEA country · 5 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 7 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