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

NCT04640987 | Recruiting Phase 1 DMC FDA Drug FDA Device

• 2 other identifiers: IRB-58549BMT 367 - T-allo10 Alpha Beta
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Hematologic Diseases

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (7)

• 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 and day 180 after αβdepleted-HSCT

• Number of participants with grade III-IV aGvHD

  Assessed at day 90 and day 180 after αβdepleted-HSCT

• Number of participants with cGvHD

  Assessed at 1 year after αβdepleted-HSCT

• Number of participants who achieved leukemia-free survival

  Assessed at 1 year after αβdepleted-HSCT

Study Arms (3)

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

Biological: Allogeneic Stem Cell Transplant; Device: CliniMACS Prodigy System; Drug: T-allo10 cells addback

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

Biological: Allogeneic Stem Cell Transplant; Device: CliniMACS Prodigy System; Drug: T-allo10 cells addback

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

Biological: Allogeneic Stem Cell Transplant; Device: CliniMACS Prodigy System; Drug: T-allo10 cells addback

Interventions

Allogeneic Stem Cell Transplant BIOLOGICAL

The allogeneic stem cell transplant involves transferring the stem cells from a healthy person (donor) to the participant via infusion.

Cohort 1; Cohort 2; Cohort 3

CliniMACS Prodigy System DEVICE

Device used for production of T-allo10 cells.

Cohort 1; Cohort 2; Cohort 3

T-allo10 cells addback DRUG

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.

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 1 Month - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• \. Age \> 1 months (with minimum weight of 10 Kg) and \< 45 years.
• \. Patients deemed eligible for allogeneic HSCT under the originating study, NCT 04249830
• \. 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.
• \. 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Porteus, Matthew, MD: lead
• California Institute for Regenerative Medicine (CIRM): collaborator

Study Sites (1)

Lucile Packard Children's Hospital

Palo Alto, California, 94305, United States

RECRUITING

MeSH Terms

Conditions

Hematologic Diseases

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases

Study Officials

• Alice Bertaina, MD, PhD

  Professor of Pediatrics, Stem Cell Transplantation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: November 17, 2020
• First Posted: November 23, 2020
• Study Start: February 10, 2021
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2029
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)