Targeted Radiotherapy in HSCT for Poor Risk Haematological Malignancy

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2012 by University Hospital Southampton NHS Foundation Trust..
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Royal Free and University College Medical School
Information provided by (Responsible Party):
Kim Orchard, Southampton University Hospitals NHS Trust
ClinicalTrials.gov Identifier:
NCT01521611
First received: January 26, 2012
Last updated: January 29, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Acute Leukaemia
Chronic Leukaemia
Myeloma
Lymphoma
Radiation: Targeted radiotherapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by University Hospital Southampton NHS Foundation Trust.:

Primary Outcome Measures:
  • Toxicities related to radiolabelled antibody. [ Time Frame: Day 30, 100, 180 and 1 year post transplant CTCAE toxicity criteria ] [ Designated as safety issue: Yes ]

    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.



Secondary Outcome Measures:
  • Dosimetry model [ Time Frame: 5 days post infusion of an Indium-111 radiolabelled anti-CD66 ] [ Designated as safety issue: Yes ]
    Dosimetry is determined by whole body and SPECT-CT of the thorax and abdomen on days 1, 2, 4 and 5 post infusion of an indium-111 radiolabelled anti-CD66. Dosimetry determines whether patients proceed to therapy with the yttrium-90 labelled anti-CD66.


Estimated Enrollment: 55
Study Start Date: January 2001
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Targeted radiotherapy
Patients receive therapy with an yttrium-90 labelled anti-CD66 following favourable dosimetry with the same antibody radiolabelled with indium-111.
Radiation: Targeted radiotherapy
Yttrium-90 labelled anti-CD66 monoclonal antibody.
Other Name: Y-90-anti-CD66

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01521611

Contacts
Contact: Kim Orchard, MBBS PhD FRCP FRCPath 0044(0)2380794163 kho@soton.ac.uk
Contact: Deborah Richardson, MA ChirB MD 0044(0)2380794163 dsr@soton.ac.uk

Locations
United Kingdom
Southampton University Hospitals NHS Trust Recruiting
Southampton, Hampshire, United Kingdom, SO16 6YD
Contact: Kim H Orchard, MBBS PhD FRCP FRCPath    0044(0)2380794163    kho@soton.ac.uk   
Principal Investigator: Kim Orchard, MBBS PhD FRCP FRCPath         
Sub-Investigator: Deborah Richardson, MA ChirB MD         
Sub-Investigator: Matthew Jenner, MBBS         
Sponsors and Collaborators
University Hospital Southampton NHS Foundation Trust.
Royal Free and University College Medical School
Investigators
Principal Investigator: Kim Orchard, MBBS PhD FRCP FRCPath University Hospital Southampton NHS Foundation Trust.
  More Information

No publications provided

Responsible Party: Kim Orchard, Chief Investigator, Southampton University Hospitals NHS Trust
ClinicalTrials.gov Identifier: NCT01521611     History of Changes
Other Study ID Numbers: RHMCAN0227
Study First Received: January 26, 2012
Last Updated: January 29, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University Hospital Southampton NHS Foundation Trust.:
Radioimmunotherapy
Transplant
BMT
yttrium
indium

Additional relevant MeSH terms:
Leukemia
Lymphoma
Hematologic Neoplasms
Chronic Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site
Hematologic Diseases
Disease Attributes
Pathologic Processes
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014