Prophylactic TCRaB+ and CD19+ Depleted Donor Lymphocyte Infusion After Allogeneic Stem Cell Transplant in High-Risk Patients With Hematologic Malignancies

Официальное название

Phase I Study of Prophylactic TCRαβ+ and CD19+ Depleted Donor Lymphocyte Infusion After Allogeneic Stem Cell Transplant in High-Risk Patients With Hematologic Malignancies

Обзор

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.

Подробное описание

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.

Вмешательства

• Устройство Allogeneic donor TCRαβ+/CD19+ cell-depleted peripheral blood mononuclear cells
  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.

Первичные конечные точки

• Incidence of Adverse Events (AEs) from DLI to day 28 post-DLI [Срок оценки: up to day 28 post-DLI (approximately day 63 on study)]
• Maximum Tolerated Dose or Maximum Administered Dose [Срок оценки: up to day 28 post-DLI (approximately day 63 on study)]

Вторичные конечные точки (12)

• Incidence of grade II-IV acute Graft-versus-Host Disease (aGVHD) after αβT/B dep-DLI [Срок оценки: up to day 28 post-DLI (approximately day 63 on study)]
• Cumulative incidence of severe grade III-IV aGVHD after αβT/B dep-DLI [Срок оценки: up to day 28 post-DLI (approximately day 63 on study)]
• Chronic Graft-versus-Host Disease (GVHD) incidence after αβT/B dep-DLI [Срок оценки: up to day 28 post-DLI (approximately day 63 on study)]
• Efficacy assessed by 1 year Progression Free Survival (PFS) [Срок оценки: up to 1 year]
• Efficacy Assessed by Non-Relapse Mortality [Срок оценки: up to 2 years]
• Efficacy Assessed by Overall Survival [Срок оценки: up to 2 years]
• Efficacy Assessed by Incidence of Cytomegalovirus (CMV) Reactivation [Срок оценки: up to 2 years]
• Efficacy Assessed by Incidence of Fungal Infection [Срок оценки: up to 2 years]
• Efficacy Assessed by Incidence of Full Chimerism (CD3 compartment) [Срок оценки: up to 2 years]
• Efficacy Assessed by Immunoglobulin Levels [Срок оценки: up to 2 years]
• Efficacy Assessed by Lymphocyte Panel Analysis [Срок оценки: up to 2 years]
• Feasibility assessed by percentage of enrolled participants who are able to receive depleted DLI [Срок оценки: up to approximately 35 days]

Критерии участия

Критерии включения

• Patients with high-risk myeloid or lymphoid malignancies determined to be eligible to undergo allo-SCT including but not limited to the conditions listed below. These criteria apply at the disease diagnosis or any time prior to the cyto-reductive therapy given before the planned conditioning:

• 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
• Myelodysplastic syndromes (MDS) with 5% or more blasts at initial diagnosis, or anytime during their treatment prior to allo-SCT.
• Myelodysplastic syndrome (MDS) high risk or very high risk per Revised International Prognostic Scoring System (IPSS-R) or Molecular International Prognostic Scoring System (IPSS-M)
• Chronic myelogenous leukemia (CML) in chronic phase failed 3 or more treatments, in accelerated or blast phase
• High risk primary myelofibrosis (PMF) per Dynamic International Prognostic Scoring System (DIPSS)-plus or Mutation-enhanced International Prognostic Scoring System for Transplant-age Patients (MIPSS70+)
• PMF in accelerated or blast 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 must be:

• Related AND
• Matched OR mismatched OR haploidentical at HLA-A, -B, -C, and -DRB1 by molecular methods
• 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.

Критерии исключения

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

• 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
• Left ventricular ejection fraction or shortening fraction < 40%

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• UW Carbone Cancer Center — Madison

Идентификаторы

NCT: NCT07285668 · 2025-1405 · UW25034 · Protocol Version 5/5/26 · SMPH/MEDICINE/HEM-ONC

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗