Targeted Radiotherapy in HSCT for Poor Risk Haematological Malignancy
Radiolabelled Anti-CD66 Monoclonal Antibody in the Conditioning Regimen Prior to Haematopoietic Stem Cell Transplantation: Phase I Study in Patients With Poor-risk Disease.
研究概览
详细说明
The aim of this clinical research study is to establish whether a radiolabelled antibody can be used to safely deliver radiotherapy to the bone marrow prior to stem cell transplantation for haematological malignancies.
With current chemotherapy regimens 60-90% of adult patients with acute leukaemia (AML and ALL) achieve a complete remission. However in a significant proportion of these patients the disease will recur. Although allogeneic and autologous bone marrow or peripheral blood haematopoietic stem cell transplantation (HSCT) are established as effective treatment options for haematological malignancies, resulting in long term disease free survival in a significant proportion of patients, the results of transplantation for patients with poor risk disease are disappointing. Further intensification of the treatment used prior to transplantation has been shown to reduce the risk of relapse, but the toxicity of the drugs or external beam radiotherapy causes an increase in transplant related deaths. The introduction of reduced intensity conditioning protocols allows the use of HSCT for older patients or those with significant additional medical problems but retrospective analysis indicates an increased rate of relapse. This is the 'Transplantation dilemma' - how to reduce the risk of disease relapse by intensifying therapy, but without an increase in toxicity to other organs causing an increase in transplant related deaths in remission.
Normal haematopoietic tissue and the malignant cells arising from it are very radiosensitive. Theoretically intensification of the conditioning therapy, particularly total body irradiation (TBI), prior to transplantation could increase tumour reduction leading to improved disease free survival rates for patients with poor risk disease. Targeted radiotherapy could allow treatment intensification without the toxicity to non-haematological tissues. In addition, the continuous, low dose rate delivered by the natural decay of a targeted radionuclide may have a greater destructive effect upon tumour cells than single dose or fractionated external beam radiation.
研究类型
注册 (实际的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习地点
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London、英国
- Royal Free Hospital and University College London
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Hampshire
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Southampton、Hampshire、英国、SO16 6YD
- Southampton University Hospitals NHS Trust
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- An underlying haematological malignancy including acute myeloid leukaemia in first complete remission (CR1) but with poor prognostic features or in >CR1 or in relapse; acute lymphoblastic leukaemia; transformed myelodysplasia, chronic myeloid leukaemia (accelerated phase or blast transformation, poor response or intolerance of tyrosine kinase inhibitors), myeloma. Patients may be in remission, partial remission or relapse.
- No concurrent or recent (within 3 weeks) chemotherapy for the underlying haematological condition
- For patients with relapsed leukaemia, bone marrow (BM) blasts must represent < 20% of BM nucleated cells.
- Although the BM remission status is not important, patients must have cellularity > 10%.
- As malignant plasma cells may or may not express CD66 antigens, patients with myeloma must have less than 30% plasma cells (as a percentage of total nucleated cells) in the BM at the time of the study.
- Age = or >18 yrs.
- WHO performance status of 0, 1 or 2 (Appendix 5).
- Predicted life-expectancy of greater than four months.
- Patients must be negative for human anti-mouse antibodies (HAMA).
Peripheral blood counts:
Wbc < 30 x 10e9/l (absolute neutrophil count >0.5 x 10e9/L) platelets > 50 x 10e9/l (platelet support is permitted)
Biochemical indices:
Plasma creatinine < 120 micromol/l (or creatinine clearance or Ethylene diamine tetra acetic acid (EDTA) clearance > 50 ml/min) Plasma bilirubin < 30 micromol/l Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) no more than 2.5 x upper limit of the normal range.
- Patient must be able to provide written informed consent.
Exclusion Criteria:
- Any serious intercurrent disease.
- Patients with BM cellularity < 10%.
- History of atopic asthma, eczema or allergy to rodent protein, confirmed history of severe allergic reactions to penicillin or streptomycin.
- Positive Human anti-murine antibodies (HAMA).
- Patients unable to provide informed consent or who are unable to co-operate for reasons of poor mental or physical health.
- Pregnancy
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 介入模型：顺序分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的：Targeted radiotherapy
Patients receive therapy with an yttrium-90 labelled anti-CD66 following favourable dosimetry with the same antibody radiolabelled with indium-111.
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Yttrium-90 labelled anti-CD66 monoclonal antibody.
其他名称：
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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 |
|---|---|---|
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Toxicities related to radiolabelled antibody.
大体时间：Up to 1 year post transplant World Health Organisation (WHO) toxicity criteria
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To determine the maximum tolerated dose (MTD) of targeted radiotherapy delivered by a murine anti-CD66 monoclonal antibody radiolabelled with yttrium-90 (Y-90) and determine the dose-limiting toxicity (DLT) in patients with haematological malignancies who are undergoing haematopoietic stem cell transplantation. Toxicities are assessed using WHO Toxicity Scale with 28 parameters. |
Up to 1 year post transplant World Health Organisation (WHO) toxicity criteria
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Dosimetry model
大体时间：5 days post infusion of an Indium-111 radiolabelled anti-CD66
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Dosimetry is determined by whole body and SPECT-CT of the thorax and abdomen on days 1, 2, 4 and 5 post infusion of an indium-111 radiolabelled anti-CD66.
Dosimetry determines whether patients proceed to therapy with the yttrium-90 labelled anti-CD66.
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5 days post infusion of an Indium-111 radiolabelled anti-CD66
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合作者和调查者
调查人员
- 首席研究员：Kim H Orchard, MBBS PhD、University Hospital Southampton NHS Foundation Trust
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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.
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