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

Porteus, Matthew, MD

Status and phase

Enrolling

Phase 1

Conditions

Hematologic Diseases

Treatments

Drug: T-allo10 cells addback

Device: CliniMACS Prodigy System

Biological: Allogeneic Stem Cell Transplant

Study type

Interventional

Funder types

Other

Identifiers

NCT04640987

IRB-58549

BMT 367 - T-allo10 Alpha Beta (Other Identifier)

Details and patient eligibility

About

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

Enrollment

22 estimated patients

Sex

All

Ages

1 month to 45 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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:

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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Single Group Assignment

Masking

None (Open label)

22 participants in 3 patient groups

Cohort 1

Experimental group

Description:

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

Treatment:

Biological: Allogeneic Stem Cell Transplant

Device: CliniMACS Prodigy System

Drug: T-allo10 cells addback

Cohort 2

Experimental group

Description:

Treatment:

Biological: Allogeneic Stem Cell Transplant

Device: CliniMACS Prodigy System

Drug: T-allo10 cells addback

Cohort 3