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
Summary
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
Arms & interventions
- BiologicalAllogeneic Stem Cell Transplant
The allogeneic stem cell transplant involves transferring the stem cells from a healthy person (donor) to the participant via infusion.
- DeviceCliniMACS Prodigy System
Device used for production of T-allo10 cells.
- DrugT-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.
Outcome measures
Primary
Recommended 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
Secondary
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
Time frame: Assessed at day 90 and day 180 after αβdepleted-HSCT
Number of participants with grade III-IV aGvHD
Time frame: Assessed at day 90 and day 180 after αβdepleted-HSCT
Number of participants with cGvHD
Time frame: Assessed at 1 year after αβdepleted-HSCT
Number of participants who achieved leukemia-free survival
Time frame: Assessed at 1 year after αβdepleted-HSCT
Number of participants with disease relapse
Time frame: Assessed at 1 year after αβdepleted-HSCT
Non-relapse mortality
Time frame: Assessed at Day 90, 1 year after αβdepleted-HSCT
Eligibility criteria
Study locations (1)
Lucile Packard Children's Hospital
Palo Alto, California, 94305