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Radiolabelled Anti-CD66 Monoclonal Antibody in the Conditioning Regimen Prior to Haematopoietic Stem Cell Transplantation: Phase I Study in Patients With Poor-risk Disease.

Phase 1/Phase 2
18 Years
75 Years
Open (Enrolling)
Acute Leukaemia, Chronic Leukaemia, Myeloma, Lymphoma

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Trial Information

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.

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

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

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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Toxicities related to radiolabelled antibody.

Outcome Description:

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.

Outcome Time Frame:

Day 30, 100, 180 and 1 year post transplant CTCAE toxicity criteria

Safety Issue:


Principal Investigator

Kim Orchard, MBBS PhD FRCP FRCPath

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Hospital Southampton NHS Foundation Trust.


United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:




Start Date:

January 2001

Completion Date:

January 2014

Related Keywords:

  • Acute Leukaemia
  • Chronic Leukaemia
  • Myeloma
  • Lymphoma
  • Radioimmunotherapy
  • Transplant
  • BMT
  • yttrium
  • indium
  • Leukemia
  • Lymphoma
  • Hematologic Neoplasms
  • Chronic Disease