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.
Primary Objectives * 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 * To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) of αβT/B dep-DLI Secondary Objectives * To assess the feasibility of αβT/B dep-DLI * To assess additional safety parameters after αβT/B dep-DLI * To assess the efficacy of αβT/B dep-DLI For the dose escalation phase: Maximum Tolerated Dose (MTD) and Maximum Administered Dose (MAD) is defined as the highest dose level where less than 2 of 6 participants experience a dose limiting toxicity (DLT). Each dose level will be followed for DLTs until day 28 post donor lymphocyte infusion (DLI). Starting at dose level 1: * If 0 of 3 participants experiences DLT, increase to next dose level for next 3 participants. * If 1 of 3 participants experience DLT, enroll 3 participants at same dose level. * If no additional DLTs (1 of 6), move on to next dose level. * If 2 of 6 participants experience DLT, enroll 3 participants into lower dose level. * If 0 or 1 participants experience DLT at lower level, this will be the MTD. Once the MTD or MAD is determined, an expansion cohort will be enrolled into that dose level. All participants will be followed for 2 years after DLI.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
38
Single 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.
UW Carbone Cancer Center
Madison, Wisconsin, United States
RECRUITINGIncidence 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.
Time frame: up to day 28 post-DLI (approximately day 63 on study)
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.
Time frame: up to day 28 post-DLI (approximately day 63 on study)
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.
Time frame: up to day 28 post-DLI (approximately day 63 on study)
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.
Time frame: up to day 28 post-DLI (approximately day 63 on study)
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.
Time frame: up to day 28 post-DLI (approximately day 63 on study)
Efficacy assessed by 1 year Progression Free Survival (PFS)
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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.
Time frame: up to 1 year
Efficacy Assessed by Non-Relapse Mortality
To assess the efficacy of prophylactic αβT/B dep-DLI after allo-SCT in high-risk patients with hematologic malignancies, non-relapse mortality will be reported.
Time frame: up to 2 years
Efficacy Assessed by Overall Survival
To assess the efficacy of prophylactic αβT/B dep-DLI after allo-SCT in high-risk patients with hematologic malignancies, overall survival will be reported.
Time frame: up to 2 years
Efficacy Assessed by Incidence of Cytomegalovirus (CMV) Reactivation
To assess the efficacy of prophylactic αβT/B dep-DLI after allo-SCT in high-risk patients with hematologic malignancies, incidence of CMV Reactivation will be reported.
Time frame: up to 2 years
Efficacy Assessed by Incidence of Fungal Infection
To assess the efficacy of prophylactic αβT/B dep-DLI after allo-SCT in high-risk patients with hematologic malignancies, incidence of fungal infections will be reported.
Time frame: up to 2 years
Efficacy Assessed by Incidence of Full Chimerism (CD3 compartment)
To assess the efficacy of prophylactic αβT/B dep-DLI after allo-SCT in high-risk patients with hematologic malignancies, incidence of full chimerism will be reported.
Time frame: up to 2 years
Efficacy Assessed by Immunoglobulin Levels
To assess the efficacy of prophylactic αβT/B dep-DLI after allo-SCT in high-risk patients with hematologic malignancies, quantitative immunoglobulin levels will be reported.
Time frame: up to 2 years
Efficacy Assessed by Lymphocyte Panel Analysis
To assess the efficacy of prophylactic αβT/B dep-DLI after allo-SCT in high-risk patients with hematologic malignancies, lymphocyte subset panel analysis will be conducted and reported.
Time frame: up to 2 years
Feasibility assessed by percentage of enrolled participants who are able to receive depleted DLI
To assess the feasibility of prophylactic αβT/B dep-DLI after allo-SCT in high-risk patients with hematologic malignancies, the percentage of enrolled participants who are able to receive depleted DLI will be reported.
Time frame: up to approximately 35 days