Targeted Radiotherapy in HSCT for Poor Risk Haematological Malignancy

NCT01521611 | Completed Phase 1

• 1 other identifier: RHMCAN0227
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 2

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.

Conditions

Acute Leukaemia; Chronic Leukaemia; Myeloma; Lymphoma

Keywords

Radioimmunotherapy; Transplant; Bone Marrow Transplant (BMT); yttrium; indium

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (1)

• Dosimetry model

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

Study Arms (1)

Targeted radiotherapy

EXPERIMENTAL

Patients receive therapy with an yttrium-90 labelled anti-CD66 following favourable dosimetry with the same antibody radiolabelled with indium-111.

Radiation: Targeted radiotherapy

Interventions

Targeted radiotherapy RADIATION

Yttrium-90 labelled anti-CD66 monoclonal antibody.

Also known as: Y-90-anti-CD66

Targeted radiotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital Southampton NHS Foundation Trust: lead
• Royal Free and University College Medical School: collaborator

Study Sites (2)

Southampton University Hospitals NHS Trust

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Royal Free Hospital and University College London

London, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 38867006 DERIVED

MeSH Terms

Conditions

Neoplasms, Plasma Cell; Lymphoma

Interventions

Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Kim H Orchard, MBBS PhD

  University Hospital Southampton NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2012
• First Posted: January 30, 2012
• Study Start: January 1, 2002
• Primary Completion: July 1, 2017
• Study Completion: July 1, 2018
• Last Updated: April 8, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)