Conformal Total Body and Marrow Irradiation for Leukemia

白血病的适形全身和骨髓照射

基本信息

  • 批准号:
    8526208
  • 负责人:
  • 金额:
    $ 29.45万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-09-13 至 2016-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Advances in conventional total body irradiation (TBI) used for bone marrow transplant regimens have been stalled for five decades due to the inherent conflict between the efficacy of high dose irradiation (i.e., reduced relapse) and radiation induced toxicity. More specifically, studies show that higher doses of radiation reduce relapse, but increase toxicity to organs at risk (OAR) including the lungs, heart, eyes, liver, and kidneys. We propose to study the feasibility of a novel technique called "adaptive total body and marrow irradiation" (adaptive TBMI). This new approach has three clear advantages: 1) Incorporation of image guided tomotherapy that allows "focused radiation" to be delivered to the target (bone marrow and other disease sites), thereby differentially delivering doses of radiation to various organs; 2) Monitoring of radiation dose delivered to the patients and adjustment of subsequent treatments (as needed) to achieve the prescribed dose, also known as the adaptive process; and, 3) Allowance for higher radiation doses (dose escalation) without increasing toxicity by using an enhanced therapeutic ratio of dose to disease sites versus dose to OARs and soft tissues. These advantages will make it possible to conduct clinical trials to determine a safe and efficacious maximum tolerated dose (MTD) of TBMI in the setting bone marrow transplant. We will conduct a feasibility trial, using adaptive TBMI techniques to: (i) provide an understanding of body motion and the accuracy of dose delivery; (ii) individualize treatment through the adaptive processes; and, (iii) improving radiobiological precision of dose escalation. The dose escalation available through the enhanced therapeutic ratio of adaptive TBMI is expected to increase efficacy (i.e. leukemia kill) without increased toxicity to healthy organs. The central hypothesis of this work is that the dose escalation of adaptive TBMI is safe and efficacious, and provides a treatment option to patients with high risk hematological malignancies. We will test this hypothesis through two aims: 1) To Determine the maximum radiation dose of TBMI by performing a phase I dose escalation study and to estimate the efficacy of this approach in a phase II study, and 2) To optimize TBMI delivery by measuring the accuracy of 3D whole body localization within the scanner, measuring the accuracy of the TBMI dose delivery, and establishing an adaptive TBMI therapy process. Subjects (0-45 years of age) with advanced, chemotherapy refractory leukemia (those who fail to achieve complete remission) will be eligible. These patients have very poor survival, with most dying from their disease within weeks to months. If successful, TBMI may offer significant benefits over TBI through better leukemia control and thus, is expected to have a significant impact on patients with advanced leukemia and other hematologic diseases. Adaptive TBMI has the potential for better disease control, reduced disease recurrence and increased patient survival, consistent with the well-established NIH scientific mission.
描述(由申请人提供):用于骨髓移植方案的常规全身照射(TBI)的进展已经停滞了五十年,这是由于高剂量照射(即,减少复发)和辐射诱导的毒性。更具体地说,研究表明,更高剂量的辐射可以减少复发,但会增加对危险器官(OAR)的毒性,包括肺、心脏、眼睛、肝脏和肾脏。我们建议研究一种新的技术称为“自适应全身和骨髓照射”(自适应TBMI)的可行性。这种新方法有三个明显的优势:1)结合图像引导断层治疗,允许将“聚焦辐射”传递到目标(骨髓和其他疾病部位),从而将不同剂量的辐射递送到各种器官; 2)监测输送给患者的辐射剂量并调整后续治疗(根据需要)以达到规定剂量,也称为适应性过程;和3)通过使用疾病部位剂量与OAR和软组织剂量的增强治疗比,允许更高的辐射剂量(剂量递增)而不增加毒性。这些优点将使进行临床试验以确定骨髓移植中TBMI的安全有效的最大耐受剂量(MTD)成为可能。我们将使用自适应TBMI技术进行可行性试验,以:(i)了解身体运动和剂量输送的准确性;(ii)通过自适应过程进行个体化治疗;(iii)提高剂量递增的放射生物学精度。通过适应性TBMI的增强治疗比可获得的剂量递增预期增加疗效(即白血病杀伤),而不会增加对健康器官的毒性。这项工作的中心假设是,适应性TBMI的剂量递增是安全和有效的,并为高风险血液恶性肿瘤患者提供了一种治疗选择。我们将通过两个目的来检验这一假设:1)通过进行I期剂量递增研究来确定TBMI的最大辐射剂量,并估计该方法在II期研究中的疗效,以及2)通过测量扫描仪内3D全身定位的准确性、测量TBMI剂量输送的准确性并建立自适应TBMI治疗过程来优化TBMI输送。患有晚期化疗难治性白血病(未能达到完全缓解的受试者)的受试者(0-45岁)将有资格入选。这些患者的生存率很低,大多数人在几周到几个月内死于这种疾病。如果成功,TBMI可能通过更好的白血病控制提供比TBI显著的益处,因此,预计对晚期白血病和其他血液病患者具有显著影响。适应性TBMI具有更好的疾病控制、减少疾病复发和增加患者生存的潜力,这与NIH的既定科学使命一致。

项目成果

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Susanta K Hui其他文献

Susanta K Hui的其他文献

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{{ truncateString('Susanta K Hui', 18)}}的其他基金

Myeloid cell-selective, oligonucleotide-based STAT3 inhibition combined with total marrow and lymphoid irradiation for immunotherapy of acute myeloid leukemia
骨髓细胞选择性、基于寡核苷酸的 STAT3 抑制联合全骨髓和淋巴照射用于急性髓系白血病的免疫治疗
  • 批准号:
    10752538
  • 财政年份:
    2023
  • 资助金额:
    $ 29.45万
  • 项目类别:
A Novel Bone Marrow Transplantation Approach for Sickle Cell Disease Using Targeted Marrow Irradiation
使用靶向骨髓照射治疗镰状细胞病的新型骨髓移植方法
  • 批准号:
    10737358
  • 财政年份:
    2023
  • 资助金额:
    $ 29.45万
  • 项目类别:
Conformal Total Body and Marrow Irradiation for Leukemia
白血病的适形全身和骨髓照射
  • 批准号:
    9283278
  • 财政年份:
    2016
  • 资助金额:
    $ 29.45万
  • 项目类别:
Conformal Total Body and Marrow Irradiation for Leukemia
白血病的适形全身和骨髓照射
  • 批准号:
    10543853
  • 财政年份:
    2011
  • 资助金额:
    $ 29.45万
  • 项目类别:
Conformal Total Body and Marrow Irradiation for Leukemia
白血病的适形全身和骨髓照射
  • 批准号:
    9888218
  • 财政年份:
    2011
  • 资助金额:
    $ 29.45万
  • 项目类别:
Conformal Total Body and Marrow Irradiation for Leukemia
白血病的适形全身和骨髓照射
  • 批准号:
    10322362
  • 财政年份:
    2011
  • 资助金额:
    $ 29.45万
  • 项目类别:
Conformal Total Body and Marrow Irradiation for Leukemia
白血病的适形全身和骨髓照射
  • 批准号:
    8184042
  • 财政年份:
    2011
  • 资助金额:
    $ 29.45万
  • 项目类别:
Conformal Total Body and Marrow Irradiation for Leukemia
白血病的适形全身和骨髓照射
  • 批准号:
    8707216
  • 财政年份:
    2011
  • 资助金额:
    $ 29.45万
  • 项目类别:
A Novel Long-Lived 41Ca Marker To Assess Bone Turnover For Breast Cancer Patients
一种用于评估乳腺癌患者骨转换的新型长效 41Ca 标记物
  • 批准号:
    7490068
  • 财政年份:
    2007
  • 资助金额:
    $ 29.45万
  • 项目类别:
A Novel Long-Lived 41Ca Marker To Assess Bone Turnover For Breast Cancer Patients
一种用于评估乳腺癌患者骨转换的新型长效 41Ca 标记物
  • 批准号:
    7304050
  • 财政年份:
    2007
  • 资助金额:
    $ 29.45万
  • 项目类别:

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