此页面是自动翻译的，不保证翻译的准确性。请参阅 英文版 对于源文本。

Naive T Cell Deplete Grafts for GVHD Prevention in Non-Malignant Diseases

2026年6月16日 更新者：Madhavi Lakkaraja、Fred Hutchinson Cancer Center

A Phase II Prospective Study Evaluating Selective Depletion of CD45RA+ (Naïve) T Cells (TND) From Peripheral Blood Stem Cell (PBSC) Grafts for Prevention of Graft Versus Host Disease (GVHD) in Non-Malignant Diseases (NMDs)

This phase II trial investigates how well a naive T cell depleted graft work for the reduction of graft versus host disease in patients with non-malignant diseases requiring hematopoietic cell transplantation. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells.

研究概览

地位

尚未招聘

条件

干预/治疗

详细说明

OUTLINE: Patients will receive CD34+ enriched CD45RA-depleted donor T-lymphocytes IV on day 0. For conditioning, patients receive cyclophosphamide by IV on day -8, fludarabine by IV on day -7 to day -3, thiotepa IV on day -7 and day -6, and undergo total-body irradiation (TBI) for 2 doses on day -2 and day -1.

GVHD Prophylaxis:

All patients also receive tacrolimus IV continuously starting on day -1, and mycophenolate mofetil (MMF) starting day 0 through day 35. If there is no evidence of grade II-IV acute GVHD on or prior to day 100, tacrolimus is tapered.

All patients also undergo bone marrow aspiration/biopsy and collection of blood samples throughout the trial.

After completion of study treatment, patients are followed up at days 7, 14, 21, 28, 56, 80, 180, and 270 and at 1, 1.5, and 2 years.

研究类型

介入性

注册 (估计的)

40

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

学习地点

  • 美国
    • Washington
      • Seattle、Washington、美国、98105
        • Seattle Children's Hospital
      • Seattle、Washington、美国、98109
        • Fred Hutchinson Cancer Center

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

  • 孩子
  • 成人

接受健康志愿者

不

描述

Inclusion Criteria:

  • Considered appropriate candidate for allogeneic HCT following low dose (4Gy) TBI containing-conditioning and have one of the following diagnoses: A) BMF B)Hemoglobinopathies C)PID D) Autoimmune cytopenias E) Immune dysregulation F) HLH G) Other NMD treatable by HCT and NMD that is not clearly defined (a patient with a NMD for whom genetic testing has been done and a genetic mutation responsible for their NMD phenotype has not been identified) are eligible for the study following discussion with and approval by the protocol PI
  • Patients aged 6 months- 5 years old (inclusive) at the time of informed consent
  • Patient with suitable HCT donor (see inclusion criteria below)
  • Recipient informed consent/assent (13 years and older), and/or legal guardian permission must be obtained

Exclusion Criteria:

  • Patient with aplastic anemia
  • Patients with severe combined immunodeficiency (SCID)
  • Fanconi anemia
  • Dyskeratosis congenita
  • Patient weight > 100 kg
  • Patients who are positive for HIV-1, HIV-2
  • Patients with current neoplastic disorders
  • Patients with uncontrolled infections for whom HCT is considered contraindicated by the consulting infectious disease physician.
  • Patients with organ dysfunction including A) Renal insufficiency B) Impaired cardiac function C)Impaired pulmonary function D) Liver dysfunction
  • Patients who are pregnant or breast-feeding
  • Patients on other experimental protocols for prevention of GVHD
  • Patients of childbearing age who are presumed to be fertile and are unwilling to use an effective birth control method or refrain from sexual intercourse during and for 12 months post-HCT
  • Patients with any other significant medical conditions that would make them unsuitable for transplantation, as determined by the PI
  • Patients with a known hypersensitivity to tacrolimus or MMF

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：非随机化
  • 介入模型：并行分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
其他：Arm A (HLA-Haploidentical or mismatched unrelated donor)
Conditioning regimen for HLA-Haploidentical or mismatched unrelated donor consisting of Cyclophosphamide (50 mg/kg x1 day), Fludarabine 35 mg/m2/day x 5 days, Thiotepa (5 mg/kg/day x 2 days), TBI (200 cGy x 2). Tacrolimus starting Day -1, MMF D0-35.
生物：ALLOGENEIC CD34+ ENRICHED AND CD45RA- DEPLETED PBSCs
CD34-selected graft with CD45RA- depleted peripheral blood stem cells given to patients with Non-Malignant Diseases
其他：Arm B (HLA-matched related or matched unrelated donor )
Conditioning regimen for HLA-matched related or matched unrelated donor consisting of Cyclophosphamide (50 mg/kg x1 day), Fludarabine (30 mg/m2/day x 5 days), Thiotepa (5 mg/kg/day x 2 days), TBI (200 cGy x 2). Tacrolimus starting Day -1, MMF D0-35.
生物：ALLOGENEIC CD34+ ENRICHED AND CD45RA- DEPLETED PBSCs
CD34-selected graft with CD45RA- depleted peripheral blood stem cells given to patients with Non-Malignant Diseases

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
GVHD-free Survival
大体时间：1 year post-transplant
Free of grade III-IV acute and NIH chronic (moderate-severe) GVHD requiring systemic immunosuppression
1 year post-transplant

次要结果测量

结果测量
措施说明
大体时间
Overall survival
大体时间：1 year post-transplant
1 year post-transplant
Transplant related mortality
大体时间：Day 100 post-transplant and 1 year post-transplant
Day 100 post-transplant and 1 year post-transplant
Graft failure
大体时间：Day 42 post-transplant
Graft failure defined as failure to achieve an ANC ≥ 0.5 × 109/L before death or second HCT, or decrease to ANC <0.1 × 109/L for 14 consecutive days (date of graft failure defined as the 14th day) after an established donor graft despite daily administration of G-CSF (SC or IV) and ≤ average 20% bone marrow cellularity on bone marrow aspirate or biopsy any time in the first 2 years following HCT. If a patient dies from organ toxicity and/or infection prior to day 28 without ANC ≥ 0.5 × 109/L this will not be considered graft failure. If the graft failure is attributed to viral infection, multi-organ failure or drug effect it will still be considered graft failure if it meets the definition of graft failure specified above.
Day 42 post-transplant
Graft rejection
大体时间：Day 100 post-transplant
Graft rejection defined as <5% donor CD3 T cell and CD33 myeloid chimerism
Day 100 post-transplant
Incidence of chronic GVHD
大体时间：At 1 year and 2 years post transplant
Defined and graded based on NIH criteria and graded operationally as the occurrence of compatible symptoms
At 1 year and 2 years post transplant
Prednisone for GVHD
大体时间：Every 3 months post-transplant for the first 2 years
Number of participants alive and off prednisone (or equivalent systemic corticosteroid) for the treatment of GVHD
Every 3 months post-transplant for the first 2 years
Incidence of opportunistic infections requiring treatment
大体时间：First year post-transplant

Proportion of participants who experience viral infections/reactivations.

  • of participants with >/= grade 1-3 viral infections
  • of participants with CMV grade 2-3
  • of participants with EBV grade 2-3
  • of participants with ADV, HHV-6 or BK >/= grade 2
  • of participants with definite (confirmed organism) viral respiratory tract infection requiring hospital admission for >/= 7 days or causing death between day 90 and day 365 post-transplant
First year post-transplant
Peripheral blood donor chimerism
大体时间：2 years post-transplant
Full donor chimerism will be defined as CD33 and CD3 ≥95%. Mixed chimerism will be defined as CD33 OR CD3 <95% but >5%. Actual chimerism values will be reported and summarized as well as dichotomized according to the 'full chimerism' and 'mixed chimerism' labels
2 years post-transplant

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Fred Hutchinson Cancer Center

调查人员

  • 首席研究员：Madhavi Lakkaraja, MD, MPH、Fred Hutch Cancer Center

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (估计的)

2026年9月1日

初级完成 (估计的)

2031年9月1日

研究完成 (估计的)

2035年9月1日

研究注册日期

首次提交

2026年6月16日

首先提交符合 QC 标准的

2026年6月16日

首次发布 (实际的)

2026年6月22日

研究记录更新

最后更新发布 (实际的)

2026年6月22日

上次提交的符合 QC 标准的更新

2026年6月16日

最后验证

2026年6月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • 20798
  • RG1126016 (其他标识符：Fred Hutch Cancer Center)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

不

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

订阅