Title
Phase I Study of Prophylactic TCRaB+ and CD19+ Depleted Donor Lymphocyte Infusion after Allogeneic Stem Cell Transplant in High-Risk Patients with Hematologic Malignancies

Description
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.

Objective
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

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

Treatment 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.

Key Eligibility Inclusion Criteria:

Patients with high-risk myeloid or lymphoid malignancies determined to be eligible to undergo a related, allo-SCT using Disease Risk Index (DRI), including the conditions listed below. These criteria apply BEFORE cyto-reductive therapy given within 28 days of planned conditioning:



Refractory acute myelogenous or lymphoid leukemia

Relapsed acute myelogenous or lymphoid leukemia

Myelodysplastic syndromes with 5 percent or more blasts

Chronic myelogenous leukemia in chronic phase 3 or more, blast phase presently, or second accelerated phase

Recurrent or refractory malignant lymphoma or Hodgkin's disease with less than a partial response at transplant

High risk chronic lymphocytic leukemia defined as no response or stable disease to the most recent treatment regimen

Other high risk hematologic malignancies for which allo-SCT is deemed clinically necessary per PI and based on institutional standards



The donor for the allo-SCT will have been identified prior to participant recruitment and must be:



Related AND

Matched OR mismatched OR haploidentical at Human Leukocyte Antigen (HLA) HLA-A, -B, -C, and -DRB1 by molecular methods



Eastern Cooperative Oncology Group (ECOG) performance score of 0-2

Ability to understand and willingness to sign written informed consent document

Willing to comply with all study procedures and be available for the duration of the study

Individuals in sexual relationships that could result in pregnancy or impregnation of their partner must use an acceptable method of contraception§ from enrollment until 4 weeks after completing study treatment.

Applicable Disease Sites
Leukemia

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital