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

NCT04328714 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: IRB00105305
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 3

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).

Conditions

Acute Leukemia; Myelodysplastic Syndromes

Keywords

Interferon Gamma (IFN γ); Graft versus Host Disease (GVHD); Allogeneic Hematopoietic Cell Transplantation

Outcome Measures

Primary Outcomes (3)

• Number of successful preparations and deliveries of investigational product

  Feasibility will be documented by successful γMSC preparation and delivery to the bedside. If an adverse event precludes initiation or completion of the infusion, this MSC preparation/infusion will, nonetheless, be considered feasible. Processing scored as a not feasible will consist of a cell preparation does not meet release criteria.

  Day 1 (day of infusion)

• Number of adverse events attributed to the investigational product

  Safety will be assessed by toxicity grading according to the Common Terminology Criteria for Adverse Events, version 4 (CTCAEv4). All recorded adverse events and serious adverse events will be documented and recorded. Their attribution to γMSCs will be determined. Dose limiting toxicity definition: For this study, dose limiting toxicities (DLTs) will be defined as any grade ≥3 adverse reaction AND attributable to γMSCs (attribution listed as at least probable), occurring from γMSC infusion through the day of hematopoietic engraftment or 21 days of transplant, whichever is later.

  Day 2 (day after infusion)

• Maximal Tolerated Dose

  The maximal tolerated dose will be the dose at which 0 of 3 or 1 of 6 subjects demonstrates a DLT. If a dose of 10 x 106 γMSCs/kg is determined to be safe, then we will not determine the true MTD and accept 10 x 106 γMSCs/kg as the maximal dose.

  Day 2 (day after infusion)

Secondary Outcomes (11)

• Primary graft failure

  Up to Year 2

• Secondary graft failure

  Up to Year 2

• Platelet engraftment

  Up to Year 2

• Non-relapse mortality (NRM)

  Up to Year 2

• Change in Acute graft-versus-host disease (aGvHD) Incidence

  Day 30, Day 100

Study Arms (2)

Adult Population

EXPERIMENTAL

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).

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

Pediatric Population

EXPERIMENTAL

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).

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

Interventions

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

Adult Population; Pediatric Population

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Edwin Horwitz: lead
• Ossium Health, Inc.: collaborator

Study Sites (3)

Children's Healthcare of Atlanta at Egleston

Atlanta, Georgia, 30322, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Graft vs Host Disease

Interventions

Interferon-gamma

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Macrophage-Activating Factors; Lymphokines; Proteins; Biological Factors

Study Officials

• Edwin Horwitz, MD, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: This study uses a rolling 6 dose escalation design with two independently accruing expansion cohorts: adults and pediatrics. Accrual in the pediatric tier will commence after the maximum dose tolerated has been determined in adults.

Study Record Dates

• First Submitted: March 30, 2020
• First Posted: March 31, 2020
• Study Start: December 2, 2021
• Primary Completion: July 20, 2022
• Study Completion: July 20, 2022
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be made available upon publication of the article and sharing will end 36 months after publication.
• Access Criteria: Data will be available to anyone upon written(email) request to the study sponsor. Requestors will need to sign a data access agreement and will be prohibited from passing it on to a third party.

Locations

US (3)