This Phase I dose-escalation trial is designed to evaluate the safety of administering rapidly -generated tumor multi-antigen associated -specific cytotoxic T lymphocytes, to HSCT recipients with high risk AML and MDS.
Aged 6 months to 80 years.
Anticipated myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant.
Patients with high risk AML and MDS who have received or will receive an allo-HSCT and have not had hematologic relapse of disease.
Karnofsky/Lansky score of ≥ 50.
Patients with uncontrolled infections.
Current evidence of GVHD > grade 2 or bronchiolitis obliterans syndrome, sclerotic GVHD, or serositis.
Pregnancy (female of childbearing potential).
Patients with high risk AML and MDS who have received an allo-HSCT and have not had hematologic relapse of disease.
Single group
Tumor associated antigen lymphocytes (TAA-T)
Biological/VaccineTAA-T may be generated from donors or recipients and will be tested for specificity to 3 tumor antigens commonly found in hematological malignancies (WT1, PRAME, and SURVIVIN,). The goal of this cell infusion will be to initiate an immune response to residual leukemia or lymphoma that includes multiple antigens and may prevent tumor evasion (through decreased expression of a single antigen).
Safety of investigational product (TAA-T)
Acute GVHD grades III-IV within 45 days of the last dose of TAA-T
Safety of TAA-T cells
Grades 3-5 infusion-related adverse events within 45 days of the last dose of TAA-T
Safety of TAA-Ts
Grades 4-5 non-hematological attributable adverse events within 45 days of TAA-T dose and that are not due to the pre-existing infection or the original malignancy or pre-existing co-morbidities as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0
Event-free survival
To determine if event-free survival (EFS) at twelve months post-HSCT is improved with TAA-T administration for AML and MDS (Arm C).
Tumor associated antigen lymphocytes (TAA-T) responses
To determine the number of patients who respond to tumor multi-antigen associated specific cytotoxic lymphocytes (TAA-T) for treatment for high risk or relapsed or refractory hematopoietic malignancies as defined by those who maintain or achieve CR, PR, MR or SD following TAA-T infusion and evaluate if this was associated with in vivo persistence of TAA-T
The incidence and severity of acute and/or chronic GVHD
To determine the incidence and severity of acute and/or chronic GVHD in patients treated with TAA-T and compare this to historical controls
Event free and overall survival
Event free and overall survival at 1 year for patients enrolled under Arm C.
Characterize the cytokine and lymphocyte cellular milieu pre- and post-infusion of TAA-T
To characterize the cytokine and lymphocyte cellular milieu pre- and post-infusion of TAAT in vivo.
Compare specificity to tumor antigens before and after TAA-T infusion
To characterize the TAA-T generated prior to infusion in terms of specificity to tumor antigens and compare this with tumor antigens present on patient samples, evaluating for in vitro activity of TAA-T.
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Catherine Bollard
Lead sponsor
Children's National Research Institute
Sponsor institution
Children's National Research Institute
Collaborator
Johns Hopkins University
Collaborator
