Clinical trial NCT01521611: Targeted Radiotherapy in HSCT for Poor Risk Haematological Malignancy
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acute Leukaemia
Chronic Leukaemia
Myeloma
Lymphoma
Keywords: Radioimmunotherapy
Transplant
Bone Marrow Transplant (BMT)
yttrium
indium
Lead sponsor: University Hospital Southampton NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Royal Free and University College Medical School
First posted: 2012-01-30
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

1. An underlying haematological malignancy including acute myeloid leukaemia in first complete remission (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, bone marrow (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 10e9/l (absolute neutrophil count \>0.5 x 10e9/L) platelets \> 50 x 10e9/l (platelet support is permitted)
11. Biochemical indices:

    Plasma creatinine \< 120 micromol/l (or creatinine clearance or Ethylene diamine tetra acetic acid (EDTA) clearance \> 50 ml/min) Plasma bilirubin \< 30 micromol/l Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) 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 Human anti-murine antibodies (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

Primary outcomes:
measure: Toxicities related to radiolabelled antibody.
timeFrame: Up to 1 year post transplant World Health Organisation (WHO) toxicity criteria
Secondary outcomes:
measure: Dosimetry model
timeFrame: 5 days post infusion of an Indium-111 radiolabelled anti-CD66
Other outcomes:
Locations:
city: Southampton
country: United Kingdom
facility: Southampton University Hospitals NHS Trust
state: Hampshire
city: London
country: United Kingdom
facility: Royal Free Hospital and University College London
Study officials:
affiliation: University Hospital Southampton NHS Foundation Trust
name: Kim H Orchard, MBBS PhD
role: PRINCIPAL_INVESTIGATOR
References: