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Acute LeukaemiaPhase 1/2NCT01521611

Targeted Radiotherapy in HSCT for Poor Risk Haematological Malignancy

A Phase 1/2 study testing Targeted radiotherapy in people with Acute Leukaemia and Chronic Leukaemia, run by University Hospital Southampton NHS Foundation Trust at 2 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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'). Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Acute Leukaemia, Chronic Leukaemia, Myeloma
What is being tested?
Targeted radiotherapy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
2 sitesUnited Kingdom
Study dates
Jan 2002to 1 Jul 2018
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • No concurrent or recent (within 3 weeks) chemotherapy for the underlying haematological condition
  • For patients with relapsed leukaemia, bone marrow (BM) blasts must represent < 20% of BM nucleated cells.
  • Although the BM remission status is not important, patients must have cellularity > 10%.
  • 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.
  • Age = or >18 yrs.
Show all 14Show fewer
  • WHO performance status of 0, 1 or 2 (Appendix 5).
  • Predicted life-expectancy of greater than four months.
  • Patients must be negative for human anti-mouse antibodies (HAMA).
  • 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)
  • 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.
  • Patient must be able to provide written informed consent.

Who cannot join

  • Any serious intercurrent disease.
  • Patients with BM cellularity < 10%.
  • History of atopic asthma, eczema or allergy to rodent protein, confirmed history of severe allergic reactions to penicillin or streptomycin.
  • Positive Human anti-murine antibodies (HAMA).
  • Patients unable to provide informed consent or who are unable to co-operate for reasons of poor mental or physical health.
  • Pregnancy

Trial locations and contacts

2 sites in 1 country.

United Kingdom2 sites

  • Royal Free Hospital and University College London

    London

  • Southampton University Hospitals NHS Trust

    Southampton, Hampshire, SO16 6YD

Other trials in United Kingdom

About this study

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.

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.

Read the 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.

Being tested
Targeted radiotherapy
Keywords
Radioimmunotherapy, Transplant, Bone Marrow Transplant (BMT), yttrium, indium
Medical subject headings
Neoplasms, Plasma Cell, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Targeted radiotherapyRadiation

    Also called Y-90-anti-CD66

    Yttrium-90 labelled anti-CD66 monoclonal antibody.

Study groups in NCT01521611
Study groupRoleWhat they receive
Targeted radiotherapyExperimentalPatients receive therapy with an yttrium-90 labelled anti-CD66 following favourable dosimetry with the same antibody radiolabelled with indium-111.
Receives: Radiation: Targeted radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Toxicities related to radiolabelled antibody.

    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 WHO Toxicity Scale with 28 parameters.

    Measured: Up to 1 year post transplant World Health Organisation (WHO) toxicity criteria

Secondary outcomes (1)

  1. Dosimetry model

    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.

    Measured: 5 days post infusion of an Indium-111 radiolabelled anti-CD66

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jan 2012 (estimated)
  2. Study startJan 2002
  3. Primary completion1 Jul 2017
  4. Study completion1 Jul 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Intervention model
Sequential
Masking
None (open label)
Enrolment
62 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01521611
Sponsor's protocol ID
RHMCAN0227
Status last verified
Apr 2019
First submitted
26 Jan 2012
Last updated
8 Apr 2019
Results posted
No
Data monitoring committee
No
Individual data sharing
No: Trial fully recruited. Data will be summarised upon completion of study.

Publications

  • Orchard K, Langford J, Guy M, Lewis G, Michopoulou S, Cooper M, Zvavamwe C, Richardson D, Lewington V. Efficient bone marrow irradiation and low uptake by non-haematological organs with an yttrium-90-anti-CD66 antibody prior to haematopoietic stem cell transplantation. Bone Marrow Transplant. 2024 Sep;59(9):1247-1257. doi: 10.1038/s41409-024-02317-z. Epub 2024 Jun 12.

    PubMed 38867006

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Targeted radiotherapy in people with Acute Leukaemia and Chronic Leukaemia, run by University Hospital Southampton NHS Foundation Trust at 2 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Toxicities related to radiolabelled antibody. (time frame: Up to 1 year post transplant World Health Organisation (WHO) toxicity criteria). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01521611, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2019.

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