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

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

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

Study Overview

• Status: Recruiting
• Conditions: Hematologic Diseases
• Intervention / Treatment: Biological: Allogeneic Stem Cell Transplant; Device: CliniMACS Prodigy System; Drug: T-allo10 cells addback

• Study Type: Interventional
• Enrollment (Estimated): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94305
      • Recruiting
      • Lucile Packard Children's Hospital
      • Sub-Investigator: Rosa Bacchetta, MD
      • Sub-Investigator: Rajni Agarwal, MD
      • Sub-Investigator: David Shyr, MD
      • Contact: Stem Cell and Gene Therapy Clinical Trials Program; Phone Number: 650-723-0912; Email: DL-SCTIntakeCoordinators@stanfordchildrens.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 41 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 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	Biological: Allogeneic Stem Cell Transplant; The allogeneic stem cell transplant involves transferring the stem cells from a healthy person (donor) to the participant via infusion.; Device: CliniMACS Prodigy System; Device used for production of T-allo10 cells.; Drug: T-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.
Experimental: Cohort 2; 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	Biological: Allogeneic Stem Cell Transplant; The allogeneic stem cell transplant involves transferring the stem cells from a healthy person (donor) to the participant via infusion.; Device: CliniMACS Prodigy System; Device used for production of T-allo10 cells.; Drug: T-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.
Experimental: Cohort 3; 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	Biological: Allogeneic Stem Cell Transplant; The allogeneic stem cell transplant involves transferring the stem cells from a healthy person (donor) to the participant via infusion.; Device: CliniMACS Prodigy System; Device used for production of T-allo10 cells.; Drug: T-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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

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 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
Number of participants with grade II-IV aGvHD	Cumulative incidence of acute GvHD (graded as II-IV using the Magic criteria)	Assessed at day 90 and day 180 after αβdepleted-HSCT
Number of participants with grade III-IV aGvHD	Cumulative incidence of acute GvHD (graded as III-IV using the Magic criteria)	Assessed at day 90 and day 180 after αβdepleted-HSCT
Number of participants who achieved 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 cGvHD	Chronic GvHD is graded according to the NIH Consensus Conference criteria	Assessed at 1 year after αβdepleted-HSCT
Non-relapse mortality	Non-relapse mortality is defined as death not preceded by recurrent primary malignancy	Assessed at Day 90, 1 year after αβdepleted-HSCT

Collaborators and Investigators

• Sponsor: Porteus, Matthew, MD
• Collaborators: California Institute for Regenerative Medicine (CIRM)
• Investigators: Principal Investigator: Alice Bertaina, MD, PhD, Professor of Pediatrics, Stem Cell Transplantation

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2021
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2029

Study Registration Dates

• First Submitted: November 17, 2020
• First Submitted That Met QC Criteria: November 17, 2020
• First Posted (Actual): November 23, 2020

Study Record Updates

• Last Update Posted (Estimated): January 8, 2026
• Last Update Submitted That Met QC Criteria: January 6, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hemic and Lymphatic Diseases; Hematologic Diseases
• Other Study ID Numbers: IRB-58549; BMT 367 - T-allo10 Alpha Beta (Other Identifier: Stanford University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes