Stem Cell Transplant From Donors After Alpha Beta Cell Depletion in Children and Adults With T-allo10 Cells Addback

Study Overview
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Brief Summary
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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 1 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

Official Title
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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

Conditions
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Hematologic Diseases

Intervention / Treatment
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* Biological: Allogeneic Stem Cell Transplant
* Device: CliniMACS Prodigy System
* Drug: T-allo10 cells addback


Participation Criteria
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Eligibility Criteria
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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: High-risk ALL in 1st CR, ALL in 2nd or subsequent CR; High-risk AML in 1st CR, AML in 2nd or subsequent CR; Myelodysplastic syndrome; JMML (Juvenile myelomonocytic leukemia); Non-Hodgkin lymphomas in 2nd or subsequent CR; 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: Patient already received αβdepleted-HSCT and has myeloid engraftment. 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.: 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.

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Stem Cell Transplant<br>The participant will undergo a stem cell transplant using donor cells that have been manipulated through an investigational device. The participant's cells will then be manipulated via a T-allo10 cell addback. Participants will be followed for outcomes for two years. | Biological: Allogeneic Stem Cell Transplant<br>* The allogeneic stem cell transplant involves transferring the stem cells from a healthy person (donor) to the participant via infusion.<br>Device: CliniMACS Prodigy System<br>* Device used for production of T-allo10 cells.<br>Drug: T-allo10 cells addback<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with myeloid engraftment after T-allo10 |  | Through day 35 (+/- 7 days) after αβdepleted-HSCT | 
| Number of participants without grade II aGvHD requiring steroids after T-allo10 |  | Through day 35 (+/- 7 days) after αβdepleted-HSCT | 
| Number of participants without grade III/IV aGvHD after T-allo10 |  | Through day 35 (+/- 7 days) after αβdepleted-HSCT | 
| Number of participants with absence of dose-limiting toxicity (DLT) 28 days following the infusion of T-allo10 given at the recommended phase 2 dose (RP2D) |  | 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). | Through Day 60 (+/- 10 days) after infusion of T-allo10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with ≥grade 3 adverse event related to T-allo10 infusion |  | Through 1 year after αβdepleted-HSCT | 
| Number of participants with grade II-IV aGvHD |  | Assessed at day 90 after αβdepleted-HSCT | 
| Number of participants with grade III-IV aGvHD |  | Assessed at day 180 after αβdepleted-HSCT | 
| Number of participants with cGvHD |  | Assessed at 1 year after αβdepleted-HSCT | 
| Leukemia-free survival | Leukemia-free survival defined as at the time of enrollment to disease relapse or death from any cause. | Assessed at 1 year after αβdepleted-HSCT | 
| Number of participants with disease relapse | Disease relapse is defined as the return of signs and symptoms of a disease after a remission. | Assessed at 1 year after αβdepleted-HSCT | 
| Non-relapse mortality |  | Assessed at Day 90 after αβdepleted-HSCT | 
| Non-relapse mortality |  | Assessed at 1 year after αβdepleted-HSCT |