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

Hematologic Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04640987
• Other study ID #: IRB-58549
• Secondary ID: BMT 367 - T-allo
• Status: Recruiting
• Phase: Phase 1
• Start date: January 20, 2020
• Est. completion date: December 2027

Study information

• Verified date: April 2024
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 22
• Est. completion date: December 2027
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 45 Years

Eligibility

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 aßdepleted-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.

Related Conditions & MeSH terms

• Hematologic Diseases

Intervention

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.

Locations

Country	Name	City	State
United States	Lucile Packard Children's Hospital	Palo Alto	California

Sponsors (2)

Lead Sponsor	Collaborator
Porteus, Matthew, MD	California Institute for Regenerative Medicine (CIRM)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with myeloid engraftment after T-allo10		Through day 35 (+/- 7 days) after aßdepleted-HSCT
Primary	Number of participants without grade II aGvHD requiring steroids after T-allo10		Through day 35 (+/- 7 days) after aßdepleted-HSCT
Primary	Number of participants without grade III/IV aGvHD after T-allo10		Through day 35 (+/- 7 days) after aßdepleted-HSCT
Primary	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)
Primary	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	Number of participants with =grade 3 adverse event related to T-allo10 infusion		Through 1 year after aßdepleted-HSCT
Secondary	Number of participants with grade II-IV aGvHD		Assessed at day 90 after aßdepleted-HSCT
Secondary	Number of participants with grade III-IV aGvHD		Assessed at day 180 after aßdepleted-HSCT
Secondary	Number of participants with cGvHD		Assessed at 1 year after aßdepleted-HSCT
Secondary	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 aßdepleted-HSCT
Secondary	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 aßdepleted-HSCT
Secondary	Non-relapse mortality		Assessed at Day 90 after aßdepleted-HSCT
Secondary	Non-relapse mortality		Assessed at 1 year after aßdepleted-HSCT