Radiolabelled Anti-CD66 Monoclonal Antibody in the Conditioning Regimen Prior to Haematopoietic Stem Cell Transplantation: Phase I Study in Patients With Poor-risk Disease.
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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Toxicities related to radiolabelled antibody.
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.
Day 30, 100, 180 and 1 year post transplant CTCAE toxicity criteria
Kim Orchard, MBBS PhD FRCP FRCPath
University Hospital Southampton NHS Foundation Trust.
United Kingdom: Medicines and Healthcare Products Regulatory Agency