CELL INTELLIGENCE · 肿瘤细胞治疗研究

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:

  1. High-risk ALL in 1st CR, ALL in 2nd or subsequent CR;
  2. High-risk AML in 1st CR, AML in 2nd or subsequent CR;
  3. Myelodysplastic syndrome;
  4. JMML (Juvenile myelomonocytic leukemia);
  5. Non-Hodgkin lymphomas in 2nd or subsequent CR;
  6. 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:

1. Patient already received αβdepleted-HSCT and has myeloid engraftment.
2. 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.:

1. Not eligible to receive HSCT on NCT04249830
2. Received another investigational agent within 30 days of enrollment.
3. Pregnancy (positive serum or urine beta-HCG) within 7 days of MNC donation.
4. 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.

主要终点：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. · 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 · 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). · Up to Day 60 (+/- 10 days) after αβdepleted-HSCT
次要终点：Number of participants with ≥grade 3 adverse event related to T-allo10 infusion；Number of participants with grade II-IV aGvHD；Number of participants with grade III-IV aGvHD；Number of participants with cGvHD；Number of participants who achieved leukemia-free survival；Number of participants with disease relapse；Non-relapse mortality

• Cohort 1 · EXPERIMENTAL · The participant will undergo a alpha-beta depleted stem cell transplant using donor cells. The participant's cells will then be manipulated via a T-allo10 cell addback to reach a dose level of 1 X 10\^5/kg
• Cohort 2 · EXPERIMENTAL · The participant will undergo a alpha-beta depleted stem cell transplant using donor cells. The participant's cells will then be manipulated via a T-allo10 cell addback to reach a dose level of 3 X 10\^5/kg
• Cohort 3 · EXPERIMENTAL · The participant will undergo a alpha-beta depleted stem cell transplant using donor cells. The participant's cells will then be manipulated via a T-allo10 cell addback to reach a dose level of 1 X 10\^6/kg

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