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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 22
- 试验地点
- 2
- 主要终点
- Recommended Phase 2 Dose (RP2D) of T-allo10 in Phase 1a
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Month 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •High-risk ALL in 1st CR, ALL in 2nd or subsequent CR;
- •High-risk AML in 1st CR, AML in 2nd or subsequent CR;
- •Myelodysplastic syndrome;
- •JMML (Juvenile myelomonocytic leukemia);
- •Non-Hodgkin lymphomas in 2nd or subsequent CR;
- •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:
- •Patient already received αβdepleted-HSCT and has myeloid engraftment.
- •Absence of active grade II aGvHD requiring >0.5 mg/Kg of steroids or any diagnosis of grade III/IVaGvHD.
排除标准
- •prior to MNC collection for Tallo-10 manufacturing.:
- •Not eligible to receive HSCT on NCT04249830
- •Received another investigational agent within 30 days of enrollment.
- •Pregnancy (positive serum or urine beta-HCG) within 7 days of MNC donation.
- •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.
研究组 & 干预措施
Cohort 1
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
干预措施: Allogeneic Stem Cell Transplant (Biological)
Cohort 1
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
干预措施: CliniMACS Prodigy System (Device)
Cohort 1
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
干预措施: T-allo10 cells addback (Drug)
Cohort 2
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
干预措施: Allogeneic Stem Cell Transplant (Biological)
Cohort 2
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
干预措施: CliniMACS Prodigy System (Device)
Cohort 2
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
干预措施: T-allo10 cells addback (Drug)
Cohort 3
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
干预措施: Allogeneic Stem Cell Transplant (Biological)
Cohort 3
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
干预措施: CliniMACS Prodigy System (Device)
Cohort 3
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
干预措施: T-allo10 cells addback (Drug)
结局指标
主要结局
Recommended Phase 2 Dose (RP2D) of T-allo10 in Phase 1a
时间窗: 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)
时间窗: 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
时间窗: 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).
次要结局
- 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)
- Number of participants with grade III-IV aGvHD(Assessed at day 90 and day 180 after αβdepleted-HSCT)
- Number of participants with cGvHD(Assessed at 1 year after αβdepleted-HSCT)
- Number of participants who achieved leukemia-free survival(Assessed at 1 year after αβdepleted-HSCT)
- Number of participants with disease relapse(Assessed at 1 year after αβdepleted-HSCT)
- Non-relapse mortality(Assessed at Day 90, 1 year after αβdepleted-HSCT)
研究者
Alice Bertaina
Professor of Pediatrics
Stanford University