Targeted Radiotherapy in HSCT for Poor Risk Haematological Malignancy
Condition: Acute Leukaemia; Chronic Leukaemia; Myeloma; Lymphoma
MeSH terms: Leukemia
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Targeted radiotherapy
Intervention type(s): Radiation
Intervention description(s): Yttrium-90 labelled anti-CD66 monoclonal antibody.
Other intervention name(s): Y-90-anti-CD66
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Radioimmunotherapy; Transplant; Bone Marrow Transplant (BMT); yttrium; indium