Stem Cell Transplant From Donors After Alpha Beta Cell Depletion in Children and Adults With T-allo10 Cells Addback
Study Details
Study Description
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 1 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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Experimental: Stem Cell Transplant The participant will undergo a stem cell transplant using donor cells that have been manipulated through an investigational device. The participant's cells will then be manipulated via a T-allo10 cell addback. Participants will be followed for outcomes for two years. |
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.
|
Outcome Measures
Primary Outcome Measures
- Number of participants with myeloid engraftment after T-allo10 [Through day 35 (+/- 7 days) after αβdepleted-HSCT]
- Number of participants without grade II aGvHD requiring steroids after T-allo10 [Through day 35 (+/- 7 days) after αβdepleted-HSCT]
- Number of participants without grade III/IV aGvHD after T-allo10 [Through 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) threshold [Through 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
- 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 after αβdepleted-HSCT]
- Number of participants with grade III-IV aGvHD [Assessed at day 180 after αβdepleted-HSCT]
- Number of participants with cGvHD [Assessed at 1 year after αβdepleted-HSCT]
- Leukemia-free survival [Assessed 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 relapse [Assessed 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 mortality [Assessed at Day 90 after αβdepleted-HSCT]
- Non-relapse mortality [Assessed at 1 year after αβdepleted-HSCT]
Eligibility Criteria
Criteria
Inclusion Criteria prior to enrollment:
-
- Age > 1 months (with minimum weight of 10 Kg) and < 45 years.
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- Patients deemed eligible for allogeneic HSCT under the originating study, NCT 04249830
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- Patients with life-threatening hematological malignancies for which HSCT has been recommended:
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High-risk ALL in 1st CR, ALL in 2nd or subsequent CR;
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High-risk AML in 1st CR, AML in 2nd or subsequent CR;
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Myelodysplastic syndrome;
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JMML (Juvenile myelomonocytic leukemia);
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Non-Hodgkin lymphomas in 2nd or subsequent CR;
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Other hematologic malignancies eligible for stem cell transplantation per institutional standard.
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- 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:
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Patient already received αβdepleted-HSCT and has myeloid engraftment.
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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.:
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Not eligible to receive HSCT on NCT04249830
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Received another investigational agent within 30 days of enrollment.
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Pregnancy (positive serum or urine beta-HCG) within 7 days of MNC donation.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Lucile Packard Children's Hospital | Palo Alto | California | United States | 94305 |
Sponsors and Collaborators
- Roncarolo, Maria Grazia, MD
- California Institute for Regenerative Medicine (CIRM)
Investigators
- Principal Investigator: Alice Bertaina, MD, PhD, Associate Professor of Pediatrics, Stem Cell Transplantation
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IRB-58549
- BMT 367 - T-allo10 Alpha Beta