Stem Cell Transplant From Donors After Alpha Beta Cell Depletion in Children and Adults With T-allo10 Cells Addback

Официальное название

Phase 1/1b Study of T-allo10 Infusion After HLA-Partially Matched Related or Unrelated TCR αβ+ T-cell/ CD19+ B-cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation (αβ Depleted-HSCT) in Children and Young Adults Affected by Hematologic Malignancies

Обзор

The purpose of this study is to determine the safety of a cell therapy, T-allo10, after αβdepleted-HSCT in the hopes that it will boost the adaptive immune reconstitution of the patient while sparing the risk of developing severe Graft-versus-Host Disease (GvHD). The primary objective of Phase 1a is to determine the recommended Phase 2 dose (RP2D) administered after infusion of αβdepleted-HSCT in children and young adults with hematologic malignancies. A Phase 1b extension will occur after dose escalation, enrolling at the RP2D for the T-allo10 cells determined in the Phase 1 portion to evaluate the safety and efficacy of infusion of T-allo10 after receipt of αβdepleted-HSCT. Additionally, Phase 1b aims to explore improvements in immune reconstitution. All participants on this study must be enrolled on another study: NCT04249830

Вмешательства

• Биопрепарат Allogeneic Stem Cell Transplant
  The allogeneic stem cell transplant involves transferring the stem cells from a healthy person (donor) to the participant via infusion.
• Устройство CliniMACS Prodigy System
  Device used for production of T-allo10 cells.
• Препарат T-allo10 cells addback
  T-allo10 cells are made by manipulating the participant's stem cell donor's white blood cells (CD4+ T cells) in the presence of their (participant's) CD14+ monocytes.

Первичные конечные точки

• Recommended Phase 2 Dose (RP2D) of T-allo10 in Phase 1a [Срок оценки: Up to 28 days after infusion of T-allo10 for each dosing cohort and Day +60 (+/- 10 days) after αβdepleted-HSCT]
• Number of participants with absence of dose-limiting toxicity (DLT) [Срок оценки: Assessed at 28 days (after infusion of T-allo10)]
• Number of participants who reach immune reconstitution (IR) threshold [Срок оценки: Up to Day 60 (+/- 10 days) after αβdepleted-HSCT]

Вторичные конечные точки (7)

• Number of participants with ≥grade 3 adverse event related to T-allo10 infusion [Срок оценки: Through 1 year after αβdepleted-HSCT]
• Number of participants with grade II-IV aGvHD [Срок оценки: Assessed at day 90 and day 180 after αβdepleted-HSCT]
• Number of participants with grade III-IV aGvHD [Срок оценки: Assessed at day 90 and day 180 after αβdepleted-HSCT]
• Number of participants with cGvHD [Срок оценки: Assessed at 1 year after αβdepleted-HSCT]
• Number of participants who achieved leukemia-free survival [Срок оценки: Assessed at 1 year after αβdepleted-HSCT]
• Number of participants with disease relapse [Срок оценки: Assessed at 1 year after αβdepleted-HSCT]
• Non-relapse mortality [Срок оценки: Assessed at Day 90, 1 year after αβdepleted-HSCT]

Критерии участия

Inclusion Criteria prior to enrollment:

• 1\. Age > 1 months (with minimum weight of 10 Kg) and < 45 years.
• 2\. Patients deemed eligible for allogeneic HSCT under the originating study, NCT 04249830
• 3\. Patients with life-threatening hematological malignancies for which HSCT has been recommended:

• High-risk ALL in 1st CR, ALL in 2nd or subsequent CR;
• High-risk AML in 1st CR, AML in 2nd or subsequent CR;
• Myelodysplastic syndrome;
• JMML (Juvenile myelomonocytic leukemia);
• Non-Hodgkin lymphomas in 2nd or subsequent CR;
• Other hematologic malignancies eligible for stem cell transplantation per institutional standard.
• 4\. All subjects ≥ 18 years of age must be able to give informed consent, or adults lacking capacity to consent must have a LAR available to provide consent. For subjects <18 years old their LAR (i.e. parent or guardian) must give informed consent. Pediatric subjects will be included in age appropriate discussion and verbal assent will be obtained for those > 7 years of age, when appropriate.

Inclusion criteria prior to T-allo10 infusion:

• Patient already received αβdepleted-HSCT and has myeloid engraftment.
• Absence of active grade II aGvHD requiring >0.5 mg/Kg of steroids or any diagnosis of grade III/IVaGvHD.

Exclusion Criteria prior to MNC collection for Tallo-10 manufacturing.:

• Not eligible to receive HSCT on NCT04249830
• Received another investigational agent within 30 days of enrollment.
• Pregnancy (positive serum or urine beta-HCG) within 7 days of MNC donation.
• Patient or donor is not willing or able to undergo an additional non-mobilized apheresis for collection of MNC prior to donation of cells for participation in NCT04249830.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Lucile Packard Children's Hospital — Palo Alto

Идентификаторы

NCT: NCT04640987 · IRB-58549 · BMT 367 - T-allo10 Alpha Beta

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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