Protocol Modifications

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.

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.

Exclusion Criteria:

• Poor organ function as follows (According to the pre-transplant workups results):

  • Creatinine greater than or equal to 2.0 mg/dL
  • Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT) greater than or equal to 5 x Upper Limit of Normal (ULN). Liver biopsy per clinician discretion.
  • Bilirubin greater than or equal to 3 x ULN (unless Gilbert's syndrome)
  • Diffusing capacity of the Lungs for Carbon Monoxide (DLCO) less than 50 percent corrected for hemoglobin
  • Left ventricular ejection fraction or shortening fraction less than 40 percent

NOTE: Exceptions to the above organ function exclusion criteria are allowable only with assent of the PI since the risks and benefits must be addressed for patients with potentially incurable hematologic malignancies. Such exceptions will be clearly documented in the subject's research record and will not be considered a deviation.

• Patients with uncontrolled intercurrent illness
• Patients with psychiatric illness/social situations that would limit compliance with study requirements

The Principal Investigator, Sponsor and funding institutions (if applicable) will ensure that all mechanisms used to share data include proper plans and safeguards to protect the rights and privacy of participants who participate in this research. Data from this study may be requested from other researchers 5 years after the completion of the primary endpoint by contacting the Principal Investigator, Dr. Hongtao Liu.

5 years after the completion of the primary endpoint