This study is being done to assess the safety and determine the maximum tolerable dose (MTD) of TCRαβ+/CD19+-depleted Donor Lymphocyte Infusion (αβT/B dep-DLI) after allogeneic stem cell transplant (allo-SCT) in highrisk patients with hematologic malignancies.
Refractory acute myelogenous (AML) or lymphoid leukemia (ALL)
Relapsed AML or ALL
AML in European LeukemiaNet (ELN) high risk per cytogenetic and mutation
Any patients with minimal residual disease (MRD+) disease by flow cytometry or with active disease (not in complete remission (CR)) prior to allo-SCT
Creatinine ≥ 2.0 mg/dL
SGOT and SGPT ≥ 5 x ULN. Liver biopsy per clinician discretion.
Bilirubin ≥ 3 x ULN (unless Gilbert's syndrome)
DLCO < 50% corrected for hemoglobin
Sequential
Allogeneic donor TCRαβ+/CD19+ cell-depleted peripheral blood mononuclear cells
DeviceSingle intravenous dose of allogeneic donor TCRαβ+/CD19+ cell-depleted peripheral blood mononuclear cells (i.e., αβT/B dep-DLI), where the dose is based on the natural killer (NK) cell (CD3-CD56+) content in the DLI product. Each participant will receive one of four DLI doses depending upon cohort to which the participant is enrolled.
Incidence of Adverse Events (AEs) from DLI to day 28 post-DLI
To assess safety of prophylactic TCRαβ+/CD19+ depleted donor lymphocyte infusion (αβT/B dep-DLI) after allogeneic stem cell transplant (allo-SCT) in high-risk patients with hematologic malignancies, incidence of AEs will be reported.
Maximum Tolerated Dose or Maximum Administered Dose
MTD/MAD defined as the highest dose level at which less than 2 of 6 participants experience a DLT.
Incidence of grade II-IV acute Graft-versus-Host Disease (aGVHD) after αβT/B dep-DLI
To assess additional safety parameters after allo-SCT in high-risk patients with hematologic malignancies, Incidence of grade II-IV aGVHD after αβT/B dep-DLI will be reported.
Cumulative incidence of severe grade III-IV aGVHD after αβT/B dep-DLI
To assess additional safety parameters after allo-SCT in high-risk patients with hematologic malignancies, cumulative incidence of severe grade III-IV aGVHD after αβT/B dep-DLI will be reported.
Chronic Graft-versus-Host Disease (GVHD) incidence after αβT/B dep-DLI
To assess additional safety parameters after allo-SCT in high-risk patients with hematologic malignancies, chronic GVHD incidence after αβT/B dep-DLI will be reported.
Efficacy assessed by 1 year Progression Free Survival (PFS)
To assess the efficacy of prophylactic αβT/B dep-DLI after allo-SCT in high-risk patients with hematologic malignancies, 1 year PFS will be reported.
Number of regulatory T cells
To assess the effect of regulatory T cells on safety and efficacy of prophylactic αβT/B dep-DLI following allo-SCT in high-risk patients with hematologic malignancies, enumeration of regulatory T cells by flow analysis of peripheral blood mononuclear cells (PBMC) using combinations of monoclonal antibodies specific for CD4, CD25, FoxP3 or CD127 will be completed and reported.
Measurable Residual Disease (MRD)
Flow cytometry will be used to assess the efficacy of αβT/B dep-DLI in eliminating MRD in patients with myeloid leukemia or Myelodysplastic Syndrome (MDS). Flow cytometry or ClonoSeq will be used for Acute Lymphoblastic Leukemia (ALL) or Chronic Lymphocytic Leukemia (CLL).
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University of Wisconsin, Madison
Lead sponsor
Miltenyi Biomedicine GmbH
Collaborator
