Back to results

Targeted Radiotherapy in HSCT for Poor Risk Haematological Malignancy

Primary Purpose

Acute Leukaemia, Chronic Leukaemia, Myeloma

Status

Completed

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

Targeted radiotherapy

About this trial

This is an interventional treatment trial for Acute Leukaemia focused on measuring Radioimmunotherapy, Transplant, Bone Marrow Transplant (BMT), yttrium, indium

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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

Sites / Locations

Southampton University Hospitals NHS Trust
Royal Free Hospital and University College London

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Targeted radiotherapy

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT01521611

First Posted

January 26, 2012

Last Updated

April 5, 2019

Sponsor

University Hospital Southampton NHS Foundation Trust

Collaborators

Royal Free and University College Medical School

1. Study Identification

Unique Protocol Identification Number

NCT01521611

Brief Title

Targeted Radiotherapy in HSCT for Poor Risk Haematological Malignancy

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.

Study Type

Interventional

2. Study Status

Record Verification Date

April 2019

Overall Recruitment Status

Completed

Study Start Date

January 2002 (Actual)

Primary Completion Date

July 1, 2017 (Actual)

Study Completion Date

July 1, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital Southampton NHS Foundation Trust

Collaborators

Royal Free and University College Medical School

4. Oversight

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Leukaemia, Chronic Leukaemia, Myeloma, Lymphoma

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Enrollment

62 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Targeted radiotherapy

Arm Type

Experimental

Arm Description

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

Intervention Type

Radiation

Intervention Name(s)

Targeted radiotherapy

Other Intervention Name(s)

Y-90-anti-CD66

Intervention Description

Yttrium-90 labelled anti-CD66 monoclonal antibody.

Primary Outcome Measure Information:

Title

Toxicities related to radiolabelled antibody.

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

Dosimetry model

Description

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kim H Orchard, MBBS PhD

Organizational Affiliation

University Hospital Southampton NHS Foundation Trust

Official's Role

Principal Investigator

Facility Information:

Facility Name

Southampton University Hospitals NHS Trust

City

Southampton

State/Province

Hampshire

ZIP/Postal Code

SO16 6YD

Country

United Kingdom

Facility Name

Royal Free Hospital and University College London

City

London

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

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

Learn more about this trial

Targeted Radiotherapy in HSCT for Poor Risk Haematological Malignancy

We'll reach out to this number within 24 hrs