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RecruitingInterventionalPhase 1

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

NCT ID: NCT04640987Sponsor: Porteus, Matthew, MDLast updated: 2026-01-08

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

Sex: AllAge: 1 Month to 45 YearsHealthy volunteers: No
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.

Study locations (1)

Lucile Packard Children's Hospital

Palo Alto, California, 94305

Recruiting
Stem Cell and Gene Therapy Clinical Trials Program · Contact
Rosa Bacchetta, MD · Sub Investigator
David Shyr, MD · Sub Investigator
Rajni Agarwal, MD · Sub Investigator