Overview

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

Eligibility

Inclusion Criteria prior to enrollment:

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1. Age > 1 months (with minimum weight of 10 Kg) and < 45 years.

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       2. Patients deemed eligible for allogeneic HSCT under the originating study, NCT
          04249830

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       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.

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       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.