Targeted Radiotherapy in HSCT for Poor Risk Haematological Malignancy
Conditions
Acute Leukaemia - Chronic Leukaemia - Myeloma - Lymphoma
Conditions: official terms
Leukemia
Conditions: Keywords
Radioimmunotherapy, Transplant, BMT, yttrium, indium
Study Type
Interventional
Study Phase
Phase 1/Phase 2
Study Design
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Targeted radiotherapy
Type: Radiation
Overall Status
Recruiting
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 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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 75 Years
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

1. An underlying haematological malignancy including acute myeloid leukaemia in CR1 but with poor prognostic features or in >CR1 or in relapse; acute lymphoblastic leukaemia; transformed myelodysplasia, chronic myeloid leukaemia (accelerated phase or blast transformation, poor response or intolerance of tyrosine kinase inhibitors), myeloma. Patients may be in remission, partial remission or relapse.

2. No concurrent or recent (within 3 weeks) chemotherapy for the underlying haematological condition

3. For patients with relapsed leukaemia, BM blasts must represent < 20% of BM nucleated cells.

4. Although the BM remission status is not important, patients must have cellularity > 10%.

5. As malignant plasma cells may or may not express CD66 antigens, patients with myeloma must have less than 30% plasma cells (as a percentage of total nucleated cells) in the BM at the time of the study.

6. Age = or >18 yrs.

7. WHO performance status of 0, 1 or 2 (Appendix 5).

8. Predicted life-expectancy of greater than four months.

9. Patients must be negative for human anti-mouse antibodies (HAMA).

10. Peripheral blood counts:

Wbc < 30 x 109/l (absolute neutrophil count >0.5 x 109/L) platelets > 50 x 109/l (platelet support is permitted)

11. Biochemical indices:

Plasma creatinine < 120 micromol/l (or creatinine clearance or EDTA clearance > 50 ml/min) Plasma bilirubin < 30 micromol/l AST no more than 2.5 x upper limit of the normal range.

12. Patient must be able to provide written informed consent.

Exclusion Criteria:

1. Any serious intercurrent disease.

2. Patients with BM cellularity < 10%.

3. History of atopic asthma, eczema or allergy to rodent protein, confirmed history of severe allergic reactions to penicillin or streptomycin.

4. Positive HAMA.

5. Patients unable to provide informed consent or who are unable to co-operate for reasons of poor mental or physical health.

6. Pregnancy
Locations
Southampton University Hospitals NHS Trust
Southampton, Hampshire, United Kingdom
Status: Recruiting
Contact: Kim H Orchard, MBBS PhD - 0044(0)2380794163 - kho@soton.ac.uk
Royal Free Hospital and University College London
London, United Kingdom
Status: Recruiting
Contact: Stephen MacKinnon, MBBS PhD
Start Date
March 2002
Completion Date
December 2016
Sponsors
University Hospital Southampton NHS Foundation Trust.
Source
University Hospital Southampton NHS Foundation Trust.
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page