Phase 1/2 Study: CD45RA Depleted Peripheral Stem Cell Addback to Prevent Viral and Fungal Infections Following Alternative Donor TCRab/CD19 Depleted Hematopoietic Stem Cell Transplant
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Evaluate number of patients with acute graft vs host disease (aGVHD)
研究概览
简要总结
The major morbidities of allogeneic hematopoietic stem cell transplant (HSCT) using donors that are not human leukocyte antigen (HLA) matched siblings are graft vs host disease (GVHD) and life- threatening infections. T cell receptor alpha beta (TCRαβ) T lymphocyte depletion and CD19+ B lymphocyte depletion of alternative donor hematopoietic stem cell (HSC) grafts is effective in preventing GVHD, but immune reconstitution may be delayed, increasing the risk of infections. The central hypothesis of this study is that an addback of CD45RO memory T lymphocytes, derived from a fraction of the original donor peripheral stem cell product depleted of CD45RA naïve T lymphocytes, will accelerate immune reconstitution and help decrease the risk of infections in TCRab/CD19 depleted PSCT.
详细描述
The risk of severe graft versus host disease (GVHD) is increased with the use of unrelated and partially matched related donors. T cell depletion reduces the risk of severe GVHD, but immune reconstitution is delayed. Important memory T cells that may protect patients from fungal and viral infections are also removed in the T depletion process. CD45RA depletion has been studied both as a single step to reduce the risk of GVHD, and also, in conjunction with αβTCR depleted hematopoietic stem cell grafts to accelerate immune reconstitution. This single institutional trial builds on data from our protocol #18-015286, NCT03810196, "CD45RA Depleted Peripheral Stem Cell Addback for Patients at Risk for Viral or Fungal Infections Post-TCRαβ/CD19 Depleted Hematopoietic Stem Cell Transplant". This prior protocol was limited to patients with hematologic malignancies using only unrelated donors as the stem cell source.
This new study will broaden the eligible diagnoses to include non-malignant transplant indications and participants with greater than or equal to 5/10 HLA matched related donors (also known as haploidentical).
This will be a phase 1 and phase 2 study depending on the donor type. Phase 1 will include patients receiving cells from mismatched/haploidentical related donors. This will be a dose escalation study to determine the maximum tolerated cell dose of the CD45RA depleted addback. Once that dose is determined, patients with this donor type will be treated as part of phase 2.
Patients receiving their cells from unrelated donors ( 9/10 or 10/10 HLA matched) will be treated as part of phase 2 with the CD45RA depleted addback cell dose that was used on our prior study. Phase 1 and phase 2 will run concurrently.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Month 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Disease for which allogeneic HSCT may be curative.
- •Remission status of hematologic malignancies and additional disease-specific eligibility determinations will be according to standards of practice within the CHOP Cellular Immunotherapy and Transplant Program (CTTS).
- •Patients must be 25 years of age and less
- •Evaluation for organ and infectious status as per our CTTS standard operating procedure.
- •Signed consent by parent/guardian or able to give consent if 18 years of age and older.
- •Participants of childbearing potential must have a negative pregnancy test as per institutional SOP.
排除标准
- •Patients who have performance score less than
- •No suitable donor available for mobilized peripheral stem cells.
- •Patients with Hodgkin lymphoma or non-Burkitt, non-lymphoblastic lymphoma.
- •Planned receipt of alemtuzumab during conditioning.
- •Patients with an available 10/10 HLA matched sibling donor.
- •Patients who do not meet institutional disease, organ or infectious criteria.
- •Donor selection and eligibility:
- •Unrelated donor meets National Marrow Donor Program criteria for donation.
- •Related donor (at least haploidentical) willing and able to donate mobilized peripheral stem cells.
- •HLA testing/matching
- •HLA testing to be done by molecular methods for A, B, C, DRB1, DQB1
- •Related donor: Must be ≥ 5/10 match
- •Unrelated donor: 10/10 or 9/10 match
- •KIR typing for haploidentical donor for hematologic malignancies
- •Donor specific HLA antibodies (DSA) should be assessed for all subjects receiving an HLA mismatched graft (≤ 9/10).
- •Donor must be willing to undergo granulocyte colony stimulating factor (GCSF) mobilization and peripheral blood stem cell collection
- •Donors must be willing to sign consent to participate in this study.
研究组 & 干预措施
Phase 1:TCRab/CD19 depleted PSCT with CD45RA depleted addback using mismatched related donors (MMRD)
Stem cell source: mobilized peripheral blood stem cells (PBSC)
Donor type: > or = 5/10 mismatched related donor
Conditioning: disease specific standard of care (SOC) regimens
干预措施: Phase 1 Dose Level 1 (Device)
Phase 1:TCRab/CD19 depleted PSCT with CD45RA depleted addback using mismatched related donors (MMRD)
Stem cell source: mobilized peripheral blood stem cells (PBSC)
Donor type: > or = 5/10 mismatched related donor
Conditioning: disease specific standard of care (SOC) regimens
干预措施: Phase 1 Dose Level 2 (Device)
Phase 1:TCRab/CD19 depleted PSCT with CD45RA depleted addback using mismatched related donors (MMRD)
Stem cell source: mobilized peripheral blood stem cells (PBSC)
Donor type: > or = 5/10 mismatched related donor
Conditioning: disease specific standard of care (SOC) regimens
干预措施: Phase 1 Dose Level 3 (Device)
Phase 2:TCRab/CD19 depleted PSCT with CD45RA depleted addback at MTD found in phase 1 using MMRD
Stem cell source: mobilized PBSC
Donor type: > or = 5/10 mismatched related donor
Conditioning: disease specific SOC regimens
干预措施: Phase 2 Maximum Tolerated Dose determined in Phase 1 (Device)
Phase 2:TCRab/CD19 depleted PSCT with CD45RA depleted addback using unrelated donors
Stem cell source: mobilized PBSC
Donor type: 9/10 or 10/10 matched unrelated donor
Conditioning: disease specific SOC regimens
干预措施: Phase 2 Established Dose from prior study, NCT03810196 (Device)
结局指标
主要结局
Evaluate number of patients with acute graft vs host disease (aGVHD)
时间窗: Up to 100 days post-transplantation
Safety evaluation assessment by cumulative incidence of acute graft vs host disease (reaction of donor immune cells against host tissues) to determine percentage of patients that develop grade 3-4 aGVHD.
Evaluate number of patients with chronic graft vs host disease (cGVHD)
时间窗: Up to 2 years post-transplantation
Safety evaluation assessment by cumulative incidence and severity of chronic GVHD (graft vs host disease that occurs more than 100 days after transplant) to determine percentage of patients that develop cGVHD.
次要结局
- Evaluate time to immune reconstitution(2 years)
- Evaluate number of patients with viral reactivation(2 years)
研究者
Timothy Olson
Medical Director, Hematopoietic Stem Cell Transplantation (HSCT) Program
Children's Hospital of Philadelphia