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
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
22
The allogeneic stem cell transplant involves transferring the stem cells from a healthy person (donor) to the participant via infusion.
Device used for production of T-allo10 cells.
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.
Lucile Packard Children's Hospital
Palo Alto, California, United States
RECRUITINGRecommended Phase 2 Dose (RP2D) of T-allo10 in Phase 1a
RP2D was determined by testing 3 different escalating doses (1x10\^5, 3x10\^5 and 1x10\^6 cells/Kg recipient body weight) in dose escalation cohorts 1 to 3 with 3 to 6 participants each. RP2D reflects the acceptable dose levels that did not cause a Dose-Limiting Toxicity (DLT) in ≥33% of participants and resulted in success with response in \>83% of participants. DLTs were defined as Grade IV aGvHD post T-allo10 infusion; any grade 3 or 4 related TEAE; any grade 3 or 4 suspected AE. Success with response was defined as achieving CD4+ IR by Day +60 (+/- 10 days) after αβdepleted-HSCT.
Time frame: 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)
Grade IV aGvHD post T-allo10 infusion; any grade 3 or 4 related treatment emergent adverse events (TEAE); any grade 3 or 4 suspected AE
Time frame: Assessed at 28 days (after infusion of T-allo10)
Number of participants who reach immune reconstitution (IR) threshold
IR (a surrogate of reduced risk of leukemia recurrence) is defined reaching the threshold of 50CD3+CD4+T-cells/µl by Day+60 (+/-10days).
Time frame: Up to Day 60 (+/- 10 days) after αβdepleted-HSCT
Number of participants with ≥grade 3 adverse event related to T-allo10 infusion
Time frame: Through 1 year after αβdepleted-HSCT
Number of participants with grade II-IV aGvHD
Cumulative incidence of acute GvHD (graded as II-IV using the Magic criteria)
Time frame: Assessed at day 90 and day 180 after αβdepleted-HSCT
Number of participants with grade III-IV aGvHD
Cumulative incidence of acute GvHD (graded as III-IV using the Magic criteria)
Time frame: Assessed at day 90 and day 180 after αβdepleted-HSCT
Number of participants with cGvHD
Chronic GvHD is graded according to the NIH Consensus Conference criteria
Time frame: Assessed at 1 year after αβdepleted-HSCT
Number of participants who achieved leukemia-free survival
Leukemia-free survival defined as at the time of enrollment to disease relapse or death from any cause.
Time frame: Assessed at 1 year after αβdepleted-HSCT
Number of participants with disease relapse
Disease relapse is defined as the return of signs and symptoms of a disease after a remission.
Time frame: Assessed at 1 year after αβdepleted-HSCT
Non-relapse mortality
Non-relapse mortality is defined as death not preceded by recurrent primary malignancy
Time frame: Assessed at Day 90, 1 year after αβdepleted-HSCT
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