Hematologic Diseases
Conditions
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
Interventions
BIOLOGICALAllogeneic Stem Cell Transplant
The allogeneic stem cell transplant involves transferring the stem cells from a healthy person (donor) to the participant via infusion.
DEVICECliniMACS Prodigy System
Device used for production of T-allo10 cells.
DRUGT-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.
Sponsors
California Institute for Regenerative Medicine (CIRM)
Porteus, Matthew, MD
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 45 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended Phase 2 Dose (RP2D) of T-allo10 in Phase 1a | Up to 28 days after infusion of T-allo10 for each dosing cohort and Day +60 (+/- 10 days) after αβdepleted-HSCT | 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. |
| Number of participants with absence of dose-limiting toxicity (DLT) | Assessed at 28 days (after infusion of T-allo10) | 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 |
| Number of participants who reach immune reconstitution (IR) threshold | Up to Day 60 (+/- 10 days) after αβdepleted-HSCT | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 aGvHD | Assessed 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 cGvHD | Assessed at 1 year after αβdepleted-HSCT | Chronic GvHD is graded according to the NIH Consensus Conference criteria |
| Number of participants who achieved 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, 1 year after αβdepleted-HSCT | Non-relapse mortality is defined as death not preceded by recurrent primary malignancy |
Countries
United States
Outcome results
None listed