Targeted Radiotherapy in HSCT for Poor Risk Haematological Malignancy
Recruitment status was Recruiting
To determine whether a radiolabelled antibody that targets the bone marrow (the 'anti-CD66') can be administered safely to patients as part of the preparative treatment prior to haematopoietic stem cell transplantation ('a bone marrow transplant'). Can the radiolabelled antibody be shown to effectively target the bone marrow in these patients. If it can, could this result in better outcomes after transplantation.
Radiation: Targeted radiotherapy
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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.|
- Toxicities related to radiolabelled antibody. [ Time Frame: Day 30, 100, 180 and 1 year post transplant CTCAE toxicity criteria ] [ Designated as safety issue: Yes ]
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 CTCAE with 28 parameters.
- Dosimetry model [ Time Frame: 5 days post infusion of an Indium-111 radiolabelled anti-CD66 ] [ Designated as safety issue: Yes ]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.
|Study Start Date:||January 2001|
|Estimated Study Completion Date:||January 2014|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
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
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 stem cell transplantation (SCT) 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 SCT 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01521611
|Contact: Kim Orchard, MBBS PhD FRCP FRCPath||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 FRCP FRCPath 0044(0)2380794163 firstname.lastname@example.org|
|Principal Investigator: Kim Orchard, MBBS PhD FRCP FRCPath|
|Sub-Investigator: Deborah Richardson, MA ChirB MD|
|Sub-Investigator: Matthew Jenner, MBBS|
|Principal Investigator:||Kim Orchard, MBBS PhD FRCP FRCPath||University Hospital Southampton NHS Foundation Trust.|