Interferon γ-Primed Mesenchymal Stromal Cells as Prophylaxis for Acute Graft v Host Disease

NCT ID: NCT04328714

Last Updated: 2025-10-15

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE1
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-02
• Study Completion Date: 2027-08-31

Brief Summary

The protocol is a phase I open label study evaluating the safety and feasibility of peri-transplant infusion of freshly expanded interferon gamma primed MSCs in adult and pediatric patients undergoing HCT for acute leukemia and myelodysplastic syndrome (MDS).

Detailed Description

Hematopoietic cell transplantation (HCT) is an established therapeutic modality for high risk hematological malignancies in adults and children. The primary cause of morbidity and mortality after HCT is graft versus host disease (GVHD), affecting up to 70% of patients even with current prophylaxis and directly accounting for approximately a third of regimen-related death. Currently, pharmacologic prophylaxis consists of a calcineurin inhibitor and methotrexate, a drug combination introduced around 40 years ago. Despite this regimen being recognized as the standard of care, it is only partially effective, increases the risk of infection and disease relapse and imparts drug-related, short- and long-term adverse effects. Mesenchymal stromal cells (MSCs) have potent immune modulatory activity which is markedly enhanced by exposure to interferon γ. In murine models, interferon γ (IFNγ) primed MSCs (γMSCs) potently suppress GVHD without untoward adverse effects suggesting this cell therapy may markedly reduce the regimen related toxicity of HCT; however γMSCs have never been infused into patients.

This protocol is designed to test the hypothesis that freshly expanded γMSCs can be reliably produced and safely infused into patients undergoing HCT as GVHD prophylaxis.

This is an investigator-initiated Phase I study using a rolling 6, dose escalation design with two independently accruing expansion cohorts: adults and pediatrics. Accrual to the pediatric tier will commence after the maximum tolerated dose (MTD) has been determined in adults. A successful outcome of this study will lay the foundation for a future Phase II study to demonstrate efficacy and support a Phase III randomized trial.

The researchers plan to enroll a minimum of 4 and maximum of 45 subjects who are greater than 1 year old. Participants will be followed for up to 2 years after the HCT. The study will be conducted at Emory University and will recruit participants from the Winship Cancer Institute and Children's Hospital in Atlanta at Egleston.

Conditions

Acute Leukemia; Myelodysplastic Syndromes

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Adult Population

Study participants aged 18 or older who are having an allogeneic blood and marrow transplant (BMT), to treat leukemia, lymphoma or other cancer of the blood will receive an infusion of mesenchymal stromal cells (MSCs).

Group Type: EXPERIMENTAL

Interferon gamma (IFNγ)-primed human bone marrow-derived mesenchymal stromal cells

Intervention Type: DRUG

To determine the maximal dose, initially adult subjects will receive a single infusion of third party, freshly ex vivo expanded, IFNγ-primed MSCs at a dose of 2 x 106 cells/kg of ideal body weight on Day +1 (the day after infusion of the hematopoietic cell graft). The dose will be escalated to 5 x 106 and then 10 x 106 cells/kg. In absence of any dose limiting toxicity, 10 x 106 cells/kg will be accepted as the maximal dose.

Subsequent participants in the adult and pediatric cohorts will receive the maximal dose as determined by the initial adult participants.

Participants will receive the infusion in an inpatient setting. MSCs will be intravenously infused through a central line or a large bore peripheral IV using standard blood product tubing within 4 hours of release. The product will be infused by IV push or syringe pump over approximately 30-60 minutes or to gravity depending on product volume.

Pediatric Population

Study participants under 18 years of age who are having an allogeneic blood and marrow transplant (BMT), to treat leukemia, lymphoma or other cancer of the blood will receive an infusion of mesenchymal stromal cells (MSCs).

Group Type: EXPERIMENTAL

Interferon gamma (IFNγ)-primed human bone marrow-derived mesenchymal stromal cells

Intervention Type: DRUG

To determine the maximal dose, initially adult subjects will receive a single infusion of third party, freshly ex vivo expanded, IFNγ-primed MSCs at a dose of 2 x 106 cells/kg of ideal body weight on Day +1 (the day after infusion of the hematopoietic cell graft). The dose will be escalated to 5 x 106 and then 10 x 106 cells/kg. In absence of any dose limiting toxicity, 10 x 106 cells/kg will be accepted as the maximal dose.

Subsequent participants in the adult and pediatric cohorts will receive the maximal dose as determined by the initial adult participants.

Participants will receive the infusion in an inpatient setting. MSCs will be intravenously infused through a central line or a large bore peripheral IV using standard blood product tubing within 4 hours of release. The product will be infused by IV push or syringe pump over approximately 30-60 minutes or to gravity depending on product volume.

Interventions

Interferon gamma (IFNγ)-primed human bone marrow-derived mesenchymal stromal cells

To determine the maximal dose, initially adult subjects will receive a single infusion of third party, freshly ex vivo expanded, IFNγ-primed MSCs at a dose of 2 x 106 cells/kg of ideal body weight on Day +1 (the day after infusion of the hematopoietic cell graft). The dose will be escalated to 5 x 106 and then 10 x 106 cells/kg. In absence of any dose limiting toxicity, 10 x 106 cells/kg will be accepted as the maximal dose.

Subsequent participants in the adult and pediatric cohorts will receive the maximal dose as determined by the initial adult participants.

Participants will receive the infusion in an inpatient setting. MSCs will be intravenously infused through a central line or a large bore peripheral IV using standard blood product tubing within 4 hours of release. The product will be infused by IV push or syringe pump over approximately 30-60 minutes or to gravity depending on product volume.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• All transplant patients who undergo HCT with a myeloablative (MA) or Fludarabine/Melphalan (RIC) conditioning regimen and a HLA A- B- C- DR-matched unrelated donor as treatment for hematologic malignancy or MDS.
• Age ≥ 1 year at the time that the informed consent document is signed.
• Patients with acute leukemia must be in complete remission (defined as an M1 marrow -<5% blasts- no evidence of extramedullary disease. Complete remissions without platelet recovery (CRp) will be considered remissions.
• Planned GVHD prophylaxis with a calcineurin inhibitor and methotrexate per institutional standards.
• Subject or parent/guardian must sign an informed consent document, and if appropriate, children must sign an assent document.

Exclusion Criteria

• Patients who are to receive a non-myeloablative conditioning regimen.
• Patients receiving another investigational drug for acute GVHD prevention during the conditioning regimen or a planned investigational drug for the first year after transplant (there are no restrictions on GVHD treatment).
• Any medical or psychological condition or situation deemed by the Investigators to put the patient at increased risk of complications or non-compliance.
• Patient with a secondary malignancy who would be otherwise eligible for study, but for whom remission from the primary disease cannot be conclusively confirmed or for whom the chance of relapse of the primary disease is significant.
• Pregnancy (positive serum b-HCG) or breastfeeding.
• Estimated glomerular filtration rate (GFR) of < 50 mL/min/1.73m2.
• Cardiac ejection fraction < 50 (using M-Mode if assessment is done by Echocardiogram)
• T bilirubin > 2 × upper limit of normal or alanine aminotransferase (ALT) > 4 × upper limit of normal or aspartate aminotransferase (AST) > 4 x upper limit of normal unresolved veno-occlusive disease
• Pulmonary disease with forced vital capacity (FVC), forced expiratory volume (FEV1) or diffusing capacity for carbon monoxide (DLCO) parameters <45% predicted (corrected for hemoglobin) or requiring supplemental oxygen. Children who are developmentally unable to perform pulmonary function testing will be assessed solely on their need for supplemental oxygen.
• Karnofsky performance score or Lansky Play-Performance Scale score <80
• Human leukocyte antigen (HLA) antibody screen positive for HLA antibodies specific against the MSC products.

• Minimum Eligible Age: 1 Year
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ossium Health, Inc.

INDUSTRY

Sponsor Role: collaborator

Edwin Horwitz

OTHER

Sponsor Role: lead

Responsible Party

Edwin Horwitz

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Edwin Horwitz, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Children's Healthcare of Atlanta at Egleston

Atlanta, Georgia, United States

Emory University

Atlanta, Georgia, United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Countries

United States

Other Identifiers

IRB00105305

Identifier Type: -

Identifier Source: org_study_id