This phase I trial tests the safety, side effects, and best dose of gamma-primed mesenchymal stromal cells in preventing acute graft versus host disease after donor stem cell transplant in patients with blood cancers or myelodysplastic syndrome. Acute graft versus host disease (AGVHD) is a condition that might occur after a donor stem cell transplant. AGVHD happens when certain white blood cells, called T-cells, in the donor cells (the graft) attack the patient's body. AGVHD causes skin, liver, stomach and intestinal problems. Mild AGVHD is often not difficult to treat. However, AGVHD can be more severe (blistering skin rash, severe or bloody diarrhea and severe jaundice). Severe cases are more difficult to treat and can be fatal. Mesenchymal stromal cells (MSCs) are cells that exist in tissues throughout the body. One place they are found is in the bone marrow. They can be obtained by needle aspiration; the same way bone marrow samples are obtained to test for leukemia. MSCs can suppress immune cells—like the ones that cause GVHD—and can promote healing. In this study, MSCs are exposed to a substance that is made by cells of the immune system (cytokine) called interferon gamma, which will activate them before they are infused. Gamma-primed mesenchymal stromal cells may work better than standard medications in preventing AGVHD.
Additional locations may be listed on ClinicalTrials.gov for NCT04328714.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVES:
I. To determine the feasibility of culture rescue of cryopreserved mesenchymal stromal cells (MSCs) with interferon gamma priming for the preparation of interferon gamma-primed human bone marrow-derived mesenchymal stromal cells (gammaMSCs) for scheduled infusion.
II. To determine the safety and toxicity of gammaMSCs infused on day +1 after matched unrelated donor hematopoietic cell transplantation (HCT) in children and adults.
III. To determine the maximum tolerated dose (MTD) of gammaMSCs infused on day +1 after matched unrelated donor HCT in adults and children.
SECONDARY OBJECTIVES:
I. To estimate the rate of severe acute graft versus host disease (GVHD) at day 100 in patients receiving gammaMSCs infused on day +1 as prophylaxis after matched unrelated donor HCT in adults and children.
II. To determine the effect of gammaMSC prophylaxis on the time to neutrophil engraftment.
III. To determine the effect of gammaMSC prophylaxis on the time to platelet engraftment at 20,000/ul.
IV. To determine the effect of gammaMSC prophylaxis on primary and secondary graft failure.
V. To determine the effect of gammaMSC prophylaxis on incidence of chronic GVHD at 1 year post HCT.
VI. To determine the 1- and 2-year non-relapse mortality (NRM), disease free survival (DFS), relapse rate and overall survival (OS).
VII. To determine the 1-year GVHD-free/relapse-free survival (GRFS).
VIII. To determine the effect of gammaMSC prophylaxis on immune reconstitution over 1 year.
IX. To determine the effect of gammaMSC prophylaxis on incidence of viral (cytomegalovirus [CMV], Epstein-Barr virus [EBV]) reactivation.
X. To determine the effect of gammaMSC prophylaxis on early and late T cell receptor (TCR) clonal diversity.
XI. To determine the effect of gammaMSC prophylaxis on the serum levels at day 7 after HCT.
XII. To determine the effect of gammaMSC prophylaxis on early T cell subset constituency.
OUTLINE: This is a phase I dose-escalation study followed by a dose-expansion study.
Patients receive gammaMSCs intravenously (IV) over 30-60 minutes one day after stem cell transplantation. Patients also undergo blood sample collection throughout the study.
After completion of study treatment, patients are followed for 24 months.
Lead OrganizationChildren's Healthcare of Atlanta - Arthur M Blank Hospital
Principal InvestigatorEdwin Mark Horwitz
