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

Phase 1
Recruiting
Conditions
Hematologic Diseases
Interventions
Device: CliniMACS Prodigy System
Drug: T-allo10 cells addback
Registration Number
NCT04640987
Lead Sponsor
Porteus, Matthew, MD
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

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
22
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Cohort 1Allogeneic Stem Cell TransplantThe 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
Cohort 1CliniMACS Prodigy SystemThe 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
Cohort 1T-allo10 cells addbackThe 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
Cohort 2Allogeneic Stem Cell TransplantThe 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
Cohort 2CliniMACS Prodigy SystemThe 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
Cohort 2T-allo10 cells addbackThe 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
Cohort 3Allogeneic Stem Cell TransplantThe 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
Cohort 3CliniMACS Prodigy SystemThe 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
Cohort 3T-allo10 cells addbackThe 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
Primary Outcome Measures
NameTimeMethod
Number of participants with myeloid engraftment after T-allo10Through day 35 (+/- 7 days) after αβdepleted-HSCT
Number of participants without grade II aGvHD requiring steroids after T-allo10Through day 35 (+/- 7 days) after αβdepleted-HSCT
Number of participants without grade III/IV aGvHD after T-allo10Through 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) thresholdThrough Day 60 (+/- 10 days) after infusion of T-allo10

IR (a surrogate of reduced risk of leukemia recurrence) is defined reaching the threshold of 50CD3+CD4+T-cells/µl by Day+60(+/-10days).

Secondary Outcome Measures
NameTimeMethod
Number of participants with ≥grade 3 adverse event related to T-allo10 infusionThrough 1 year after αβdepleted-HSCT
Number of participants with grade II-IV aGvHDAssessed at day 90 and day 180 after αβdepleted-HSCT

Cumulative incidence of acute GvHD (graded as II-IV using the Magic criteria)

Number of participants with grade III-IV aGvHDAssessed at day 90 and day 180 after αβdepleted-HSCT

Cumulative incidence of acute GvHD (graded as III-IV using the Magic criteria)

Number of participants with cGvHDAssessed at 1 year after αβdepleted-HSCT
Number of participants who achieved leukemia-free survivalAssessed at 1 year after αβdepleted-HSCT

Leukemia-free survival defined as at the time of enrollment to disease relapse or death from any cause.

Number of participants with disease relapseAssessed at 1 year after αβdepleted-HSCT

Disease relapse is defined as the return of signs and symptoms of a disease after a remission.

Non-relapse mortalityAssessed at 1 year after αβdepleted-HSCT

Trial Locations

Locations (1)

Lucile Packard Children's Hospital

🇺🇸

Palo Alto, California, United States

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