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| ID | Type | Description | Link |
|---|---|---|---|
| BMT 367 - T-allo10 Alpha Beta | Other Identifier | Stanford University |
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| Name | Class |
|---|---|
| California Institute for Regenerative Medicine (CIRM) | OTHER |
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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | 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 |
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| Cohort 2 | Experimental | 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 3 X 10^5/kg |
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| Cohort 3 | Experimental | 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 10^6/kg |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Allogeneic Stem Cell Transplant | Biological | The allogeneic stem cell transplant involves transferring the stem cells from a healthy person (donor) to the participant via infusion. |
| Measure | Description | Time Frame |
|---|---|---|
| Recommended Phase 2 Dose (RP2D) of T-allo10 in Phase 1a | RP2D was determined by testing 3 different escalating doses (1x10^5, 3x10^5 and 1x10^6 cells/Kg recipient body weight) in dose escalation cohorts 1 to 3 with 3 to 6 participants each. RP2D reflects the acceptable dose levels that did not cause a Dose-Limiting Toxicity (DLT) in ≥33% of participants and resulted in success with response in >83% of participants. DLTs were defined as Grade IV aGvHD post T-allo10 infusion; any grade 3 or 4 related TEAE; any grade 3 or 4 suspected AE. Success with response was defined as achieving CD4+ IR by Day +60 (+/- 10 days) after αβdepleted-HSCT. | Up to 28 days after infusion of T-allo10 for each dosing cohort and Day +60 (+/- 10 days) after αβdepleted-HSCT |
| Number of participants with absence of dose-limiting toxicity (DLT) | Grade IV aGvHD post T-allo10 infusion; any grade 3 or 4 related treatment emergent adverse events (TEAE); any grade 3 or 4 suspected AE | Assessed at 28 days (after infusion of T-allo10) |
| 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). | Up to Day 60 (+/- 10 days) after αβdepleted-HSCT |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Cumulative incidence of acute GvHD (graded as II-IV using the Magic criteria) |
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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:
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:
Exclusion Criteria prior to MNC collection for Tallo-10 manufacturing.:
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| Name | Affiliation | Role |
|---|---|---|
| Alice Bertaina, MD, PhD | Professor of Pediatrics, Stem Cell Transplantation | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Lucile Packard Children's Hospital | Recruiting | Palo Alto | California | 94305 | United States |
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| CliniMACS Prodigy System | Device | Device used for production of T-allo10 cells. |
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| T-allo10 cells addback | Drug | 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. |
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| Assessed at day 90 and day 180 after αβdepleted-HSCT |
| Number of participants with grade III-IV aGvHD | Cumulative incidence of acute GvHD (graded as III-IV using the Magic criteria) | Assessed at day 90 and day 180 after αβdepleted-HSCT |
| Number of participants with cGvHD | Chronic GvHD is graded according to the NIH Consensus Conference criteria | Assessed at 1 year after αβdepleted-HSCT |
| Number of participants who achieved 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 αβdepleted-HSCT |
| 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 αβdepleted-HSCT |
| Non-relapse mortality | Non-relapse mortality is defined as death not preceded by recurrent primary malignancy | Assessed at Day 90, 1 year after αβdepleted-HSCT |
| ID | Term |
|---|---|
| D006402 | Hematologic Diseases |
| ID | Term |
|---|---|
| D006425 | Hemic and Lymphatic Diseases |
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