Targeted Radiotherapy in HSCT for Poor Risk Haematological Malignancy
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01521611|
Recruitment Status : Recruiting
First Posted : January 30, 2012
Last Update Posted : October 17, 2016
|Condition or disease||Intervention/treatment||Phase|
|Acute Leukaemia Chronic Leukaemia Myeloma Lymphoma||Radiation: Targeted radiotherapy||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||55 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Radiolabelled Anti-CD66 Monoclonal Antibody in the Conditioning Regimen Prior to Haematopoietic Stem Cell Transplantation: Phase I Study in Patients With Poor-risk Disease.|
|Study Start Date :||March 2002|
|Estimated Primary Completion Date :||December 2017|
|Estimated Study Completion Date :||December 2018|
Experimental: Targeted radiotherapy
Patients receive therapy with an yttrium-90 labelled anti-CD66 following favourable dosimetry with the same antibody radiolabelled with indium-111.
Radiation: Targeted radiotherapy
Yttrium-90 labelled anti-CD66 monoclonal antibody.
Other Name: Y-90-anti-CD66
- Toxicities related to radiolabelled antibody. [ Time Frame: Up to 1 year post transplant World Health Organisation (WHO) toxicity criteria ]
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.
- Dosimetry model [ Time Frame: 5 days post infusion of an Indium-111 radiolabelled anti-CD66 ]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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01521611
|Contact: Kim H Orchard, MBBS PhD||0044(0)firstname.lastname@example.org|
|Contact: Deborah Richardson, MA ChirB MD||0044(0)email@example.com|
|Southampton University Hospitals NHS Trust||Recruiting|
|Southampton, Hampshire, United Kingdom, SO16 6YD|
|Contact: Kim H Orchard, MBBS PhD 0044(0)2380794163 firstname.lastname@example.org|
|Principal Investigator: Kim Orchard, MBBS PhD|
|Sub-Investigator: Deborah Richardson, MA ChirB MD|
|Sub-Investigator: Matthew Jenner, MBBS|
|Royal Free Hospital and University College London||Recruiting|
|London, United Kingdom|
|Contact: Stephen MacKinnon, MBBS PhD|
|Contact: Ronjon Chakraverty, MBBS PhD|
|Principal Investigator:||Kim H Orchard, MBBS PhD||University Hospital Southampton NHS Foundation Trust|