Preemptive Infusion of Donor Lymphocytes Depleted of TCR + T Cells + CD19+ B Cells Following ASCT

Leland Metheny

Overview

The purpose of this study is to reduce the risk of cancer relapse by giving a donor lymphocyte infusion (DLI) to boost the immune system early after a stem cell transplant so that leukemia cells that escaped chemotherapy can be detected and killed. This DLI will contain mostly lymphocytes that have graft versus tumor effect with low risk of graft versus host disease. Because the process of giving a DLI in the first four weeks after a transplant has not been approved by the Food and Drug Administration (FDA), this study in investigational (experimental).

The primary objective of this study is to investigate if donor lymphocytes depleted of TCR-αβ T cells and B cells can be infused on Day 28 following allogeneic stem cell transplantation without inducing Grade III-IV graft versus host disease, Grade II GVHD requiring systemic treatment and or new onset, severe neutropenia requiring growth factor support. This study also seeks to characterize the lymphocyte subsets obtained following depletion of TCR-αβ T cells and B cells from non-mobilized, leukapheresis products. Additionally, this study will attempt to describe occurrence of disease relapse and to describe the occurrence of post-transplant re- activation and/or infections with viruses such as CMV, and EBV.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Conditions

Allogeneic Stem Cell Transplant Candidate Acute Myeloid/Lymphoblastic Leukemia Myelodysplastic Syndrome Myeloproliferative Neoplasm Lymphoproliferative Disorders

Interventions

Cellular therapy productBIOLOGICAL

Cellular therapy product: Allogeneic transplant donor lymphocytes, depleted of TCR-αβ T cells and B cells; enriched for NK cells and TCRγδ T cells. * Infused using venous catheter on post-transplant Day 28 (+ 7 days). * Single infusion of entire lymphocyte product derived from two-blood volume leukapheresis (non-mobilized).

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Subjects must have histologic or cytologic confirmation of ANY hematologic malignancy * Allogeneic stem cell transplant is indicated as management of underlying hematologic malignancy. * Participant has organ function (cardiac, lung and liver) considered adequate to undergo conditioning chemotherapy and allogeneic stem cell transplant in the assessment of the clinical program * Participant has a 10/10 HLA-matched sibling donor OR has a HLA-haploidentical donor available (in the absence of a 10/10 HLA matched unrelated donor) * The related transplant donor is willing, available and consents to undergo a second, non-mobilized leukapheresis for the procurement of donor lymphocytes * The related transplant donor is 18 years of age or older * Subjects must have the ability to understand and the willingness to sign a written informed consent document or provide assent. Exclusion Criteria: * Subject is unwilling to receive a prophylactic donor lymphocyte infusion per study protocol. * The related donor is unwilling or unavailable to undergo a second, non- mobilized leukapheresis for the procurement of donor lymphocytes. * Women of child-bearing potential and men must agree to use adequate contraception (double barrier method of birth control or abstinence) 4 weeks prior to study entry and for the duration of study participation. Women of child-bearing age must have documented negative pregnancy test prior to start of conditioning regimen for stem cell transplantation and a repeat negative pregnancy test prior to infusion of the lymphocyte product. * Patients with any of the following organ function abnormalities: Left ventricular ejection fraction (LVEF) \< 45%; DLCO \<45% of expected value corrected for alveolar volume and hemoglobin; Serum Creatinine \>2 times the upper limit of normal.

Locations (1)

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Outcomes

Primary Outcomes

Incidence of Grade III-IV GVHD, Grade II GVHD requiring systemic treatment or new onset, severe neutropenia requiring growth factor support at Day 100 and T+6 months.

This study seeks to measure if donor lymphocytes depleted of TCR-αβ T cells and B cells can be infused on Day 28 following allogeneic stem cell transplantation without inducing Grade III-IV graft versus host disease, Grade II GVHD requiring systemic treatment or new onset, severe neutropenia requiring growth factor support. The endpoint associated with this objective is 'incidence of Grade III-IV graft versus host disease, Grade II GVHD requiring systemic treatment or new onset, severe neutropenia requiring growth factor support at Day 100 and T+6 months.'

Time frame: up to 30 days after lymphocyte product infusion

Secondary Outcomes

Different lymphocyte types in the infused product reported as cells per kilogram body weight of the recipient

Number of different lymphocyte types in the infused product measured as cells per kilogram body weight of the recipient

Time frame: 28 days post-transplant

Number of disease relapse events in the first 6 moths following stem cell transplant

To describe occurrence of disease relapse, the number of disease relapse events in the first year following stem cell transplant will be reported.

Time frame: 6 months from start of treatment

Number of disease relapse events in the first 1 year following stem cell transplant

To describe occurrence of disease relapse, the number of disease relapse events in the first year following stem cell transplant will be reported.

Time frame: 1 year from start of treatment

Average time to disease relapse from date of transplant

To describe occurrence of disease relapse, the average time to disease relapse from date of transplant in the first six months following stem cell transplant will be reported.

Data from ClinicalTrials.gov

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