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
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
High-risk ALL in 1st CR, ALL in 2nd or subsequent CR;
High-risk AML in 1st CR, AML in 2nd or subsequent CR;
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.
Single group
Allogeneic Stem Cell Transplant
Biological/VaccineThe allogeneic stem cell transplant involves transferring the stem cells from a healthy person (donor) to the participant via infusion.
CliniMACS Prodigy System
DeviceDevice used for production of T-allo10 cells.
T-allo10 cells addback
DrugT-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.
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.
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
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).
Number of participants with ≥grade 3 adverse event related to T-allo10 infusion
Number of participants with grade II-IV aGvHD
Cumulative incidence of acute GvHD (graded as II-IV using the Magic criteria)
Number of participants with grade III-IV aGvHD
Cumulative incidence of acute GvHD (graded as III-IV using the Magic criteria)
Number of participants with cGvHD
Chronic GvHD is graded according to the NIH Consensus Conference criteria
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Porteus, Matthew, MD
Lead sponsor
Stanford University
Sponsor institution
California Institute for Regenerative Medicine (CIRM)
Collaborator
