Clinical trial NCT04640987: Stem Cell Transplant From Donors After Alpha Beta Cell Depletion in Children and Adults With T-allo10 Cells Addback
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Hematologic Diseases
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: California Institute for Regenerative Medicine (CIRM)
First posted: 2020-11-23
Enrollment: 22
Sex: ALL
Minimum age (years): 1
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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:

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.

Primary outcomes:
measure: Number of participants with myeloid engraftment after T-allo10
timeFrame: Through day 35 (+/- 7 days) after αβdepleted-HSCT
measure: Number of participants without grade II aGvHD requiring steroids after T-allo10
timeFrame: Through day 35 (+/- 7 days) after αβdepleted-HSCT
measure: Number of participants without grade III/IV aGvHD after T-allo10
timeFrame: Through day 35 (+/- 7 days) after αβdepleted-HSCT
measure: 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)
timeFrame: Assessed at 28 days (after infusion of T-allo10)
measure: Number of participants who reach immune reconstitution (IR) threshold
timeFrame: Through Day 60 (+/- 10 days) after infusion of T-allo10
Secondary outcomes:
measure: Number of participants with ≥grade 3 adverse event related to T-allo10 infusion
timeFrame: Through 1 year after αβdepleted-HSCT
measure: Number of participants with grade II-IV aGvHD
timeFrame: Assessed at day 90 and day 180 after αβdepleted-HSCT
measure: Number of participants with grade III-IV aGvHD
timeFrame: Assessed at day 90 and day 180 after αβdepleted-HSCT
measure: Number of participants with cGvHD
timeFrame: Assessed at 1 year after αβdepleted-HSCT
measure: Number of participants who achieved leukemia-free survival
timeFrame: Assessed at 1 year after αβdepleted-HSCT
measure: Number of participants with disease relapse
timeFrame: Assessed at 1 year after αβdepleted-HSCT
measure: Non-relapse mortality
timeFrame: Assessed at Day 90 after αβdepleted-HSCT
measure: Non-relapse mortality
timeFrame: Assessed at 1 year after αβdepleted-HSCT
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital
state: California
Study officials:
affiliation: Associate Professor of Pediatrics, Stem Cell Transplantation
name: Alice Bertaina, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: