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Targeted Radiotherapy in HSCT for Poor Risk Haematological Malignancy

5 april 2019 uppdaterad av: University Hospital Southampton NHS Foundation Trust

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.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Faktisk)

62

Fas

  • Fas 2
  • Fas 1

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Storbritannien
      • London, Storbritannien
        • Royal Free Hospital and University College London
    • Hampshire
      • Southampton, Hampshire, Storbritannien, SO16 6YD
        • Southampton University Hospitals NHS Trust

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år till 75 år (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Interventionsmodell: Sekventiell tilldelning
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Targeted radiotherapy
Patients receive therapy with an yttrium-90 labelled anti-CD66 following favourable dosimetry with the same antibody radiolabelled with indium-111.
Strålning: Targeted radiotherapy
Yttrium-90 labelled anti-CD66 monoclonal antibody.
Andra namn:
  • Y-90-anti-CD66

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Toxicities related to radiolabelled antibody.
Tidsram: Up to 1 year post transplant World Health Organisation (WHO) toxicity criteria

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

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Dosimetry model
Tidsram: 5 days post infusion of an Indium-111 radiolabelled anti-CD66
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.
5 days post infusion of an Indium-111 radiolabelled anti-CD66

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

University Hospital Southampton NHS Foundation Trust

Samarbetspartners

Royal Free and University College Medical School

Utredare

  • Huvudutredare: Kim H Orchard, MBBS PhD, University Hospital Southampton Nhs Foundation Trust

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

1 januari 2002

Primärt slutförande (Faktisk)

1 juli 2017

Avslutad studie (Faktisk)

1 juli 2018

Studieregistreringsdatum

Först inskickad

26 januari 2012

Först inskickad som uppfyllde QC-kriterierna

26 januari 2012

Första postat (Uppskatta)

30 januari 2012

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

8 april 2019

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

5 april 2019

Senast verifierad

1 april 2019

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • RHMCAN0227

Plan för individuella deltagardata (IPD)

Planerar du att dela individuella deltagardata (IPD)?

NEJ

IPD-planbeskrivning

Trial fully recruited. Data will be summarised upon completion of study.

Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .

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