Targeted Radiotherapy in HSCT for Poor Risk Haematological Malignancy
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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. |
- 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.
- 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 |
Inclusion Criteria:
- 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.
- No concurrent or recent (within 3 weeks) chemotherapy for the underlying haematological condition
- For patients with relapsed leukaemia, 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 109/l (absolute neutrophil count >0.5 x 109/L) platelets > 50 x 109/l (platelet support is permitted)
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.
- 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 HAMA.
- Patients unable to provide informed consent or who are unable to co-operate for reasons of poor mental or physical health.
- Pregnancy
Contacts and Locations| 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 |
| 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 | |
| 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 May 23, 2013