A Randomised Phase II Clinical Trial Using Targeted Radiotherapy Delivered by an Yttrium-90 Radio-Labelled Anti-CD66 Monoclonal Antibody With High Dose Melphalan Compared to Melphalan Alone, Prior to Autologous Stem Cell Transplantation for Multiple Myeloma
- To determine the efficacy of high-dose melphalan (200mg/m²) in combination with
targeted radiotherapy delivered by yttrium Y 90 anti-CD66 monoclonal antibody
BW250/183, in terms of disease response (complete remission rate and change in serum
free light chain level before and after treatment with yttrium Y 90 anti-CD66
monoclonal antibody BW250/183), in patients undergoing autologous hematopoietic stem
cell transplantation for multiple myeloma.
- To determine the toxicity profile of yttrium Y 90 anti-CD66 monoclonal antibody
BW250/183 in the context of autologous hematopoietic stem cell transplantation.
- To determine the effect of targeted radiotherapy on other parameters of disease
response, in terms of proportion of patients with partial remission, stable disease,
and progressive disease, remission duration (time to disease progression), and overall
- To determine the effect of targeted radiotherapy on engraftment when used in
combination with high-dose melphalan in patients undergoing autologous hematopoietic
stem cell transplantation for multiple myeloma.
- To investigate the pharmacokinetic behavior of indium In 111 anti-CD66 monoclonal
antibody BW250/183 (used for dosimetry).
- To continue to develop a dosimetry model based on single-photon emission computed
tomography (SPECT) and whole body gamma camera imaging following administration of the
radiolabeled anti-CD66 monoclonal antibody (in a subset of patients at the Southampton
- To assess the proportion of patients who form human anti-murine antibodies (HAMA) after
treatment with targeted radiotherapy in the context of an autologous hematopoietic stem
OUTLINE: This is a multicenter study. Patients are stratified according to disease risk
group (low risk [beta-2 microglobulin and C-reactive protein < 6 or either beta-2
microglobulin or C-reactive protein ≥ 6] vs high risk [both beta-2 microglobulin and
C-reactive protein ≥ 6]). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive a dosimetry dose of indium In 111 anti-CD66 monoclonal antibody
BW250/183 IV on day 1 and undergo gamma camera imaging and serial blood samples on days
1-5. Patients then receive a therapeutic dose of yttrium Y 90 anti-CD66 monoclonal
antibody BW250/183 IV once between days 9 and 16 and high-dose melphalan IV on day 28.
Patients then undergo autologous hematopoietic stem cell transplantation (HSCT) on day
- Arm II: Patients receive high-dose melphalan IV on day 1. Patients then undergo
autologous HSCT on day 3.
Patients in arm I undergo blood sample collection periodically for pharmacokinetic and
pharmacodynamic studies and analysis of human anti-murine antibody (HAMA) status.
After completion of study treatment, patients are followed periodically.
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Remission status pre- and post-transplantation, specifically the number of patients who achieve complete remission, as measured by the European Blood and Marrow Transplantation Organization Response Criteria
Kim Orchard, MD
University Hospital Southampton NHS Foundation Trust.