Contact information
Type
Scientific
Primary contact
Dr Kim Orchard
ORCID ID
Contact details
Senior Lecturer and Consultant Haematologist
Department of Haematology
Level C
Mailpoint 8
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom
+44 (0)2380 794 163
kho@soton.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT00637767
Protocol/serial number
1
Study information
Scientific title
A randomised phase II clinical trial using targeted radiotherapy delivered by an yttrium-90 radio-labelled Anti-CD66 monoclonal antibody with high dose melphalan compared to melphalan alone, prior to autologous stem cell transplantation for multiple myeloma
Acronym
Anti-CD66
Study hypothesis
To determine the efficacy of targeted radiotherapy delivered by an Yttrium-90 (90Y)-radio-labelled murine anti-CD66 monoclonal antibody, given in addition to high dose melphalan (200 mg/m^2) in terms of disease response (complete remission rate and change of serum free light chain level pre and post yttrium-90-radio-labelled anti-CD66) in patients undergoing haematopoietic stem cell transplantation (HSCT) for multiple myeloma.
Ethics approval
Southampton and South West Hampshire Research Ethics Committee (A), 09/01/2007
Study design
Multicentre randomised non-blind phase II study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Multiple myeloma
Intervention
There are two treatment arms comparing two transplant conditioning schedules prior to autologous stem cell rescue.
Arm A: high dose melphalan (200 mg/m^2) plus targeted radiotherapy:
Patients will undergo a dosimetry assessment by way of a Indium-111 radiolabelled anti-CD66 monoclonal antibody. This will be infused for 15 minutes. Two to four weeks later patients will receive targeted radiotherapy with Yttrium-90 radiolabelled anti-CD66 monoclonal antibody infused for 15 minutes. Two weeks later patients will receive the standard pre-conditioning regimen of high dose melphalan (200 mg/m^2) prior to autologous stem cell transplantation.
Arm B: high dose melphalan (200 mg/m^2) alone:
No targeted radiotherapy.
All patients will be followed up for 12 months post-transplant.
Intervention type
Drug
Phase
Phase II
Drug names
Melphalan
Primary outcome measure
Remission status pre- and post-transplantation, as defined for multiple myeloma by the European Blood and Marrow Transplantation (EBMT) organisation. Specifically the number of patients in each arm achieving CR as defined in the EBMT response criteria; remission status up to 12 months post transplant.
Secondary outcome measures
1. Disease response in both arms as determined from changes in serum free light chains (in those patients in whom serum free light chains are informative), up to 12 months post-transplant
2. Disease response excluding CR rates; proportion of patients with PR, stable disease (SD), progressive disease (PD), remission duration (time to disease progression), up to 12 months post-transplant
3. Engraftment quality as determined by time to recovery of peripheral blood neutrophils to greater than 0.5 x 10^9/l, platelets greater than 50 x 10^9/l and duration of recovery for greater than 180 days post-transplant, up to four weeks post-transplant
4. The treatment related mortality (TRM) and overall survival (OS) between the two arms, up to 12 months post-transplant
5. To determine the toxicity profile of 90Y-radiolabelled anti-CD66 MAb in the context of autologous stem cell transplantation, up to 12 months post-transplant
6. Pharmacokinetics of 111-in-radiolabelled anti-CD66 MAb as determined from serial blood samples, serial planar and single photon emission computed tomography (SPECT) gamma-camera imaging of selected organs, up to day five post-infusion
7. To continue to develop a dosimetry model based on SPECT and whole body gamma camera imaging, up to day post-dosimetry
8. To assess the proportion of patients that form human anti-murine antibodies (HAMA) following exposure to anti-CD66 MAb in the context of an autologous stem cell transplant, up to 12 months post-transplant
Overall trial start date
01/05/2007
Overall trial end date
17/12/2013
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Histologically or cytologically proven multiple myeloma
2. In partial remission (PR) after chemotherapy and before priming therapy for stem cell mobilisation
3. Aged greater than 18 years
4. Life expectancy of at least 24 weeks
5. World Health Organization (WHO) performance status of less than two
6. Haematological and biochemical indices (these measurements must be performed within one week prior to the patient going on study):
6.1. Haemoglobin (Hb) greater than or equal to 9.0 g/dl
6.2. Neutrophils greater than or equal to 1.5 x 10^9/L
6.3. Platelets (Plts) greater than or equal to 50 x 10^9/L
7. Any of the following abnormal baseline liver function tests:
7.1. Serum bilirubin less than or equal to 1.5 x upper normal limit
7.2. Alanine amino-transferase (ALT) and/or aspartate amino-transferase (AST) less than or equal to 2.5 x Upper Limit of Normal (ULN)
8. The following abnormal baseline renal function test:
8.1. Calculated creatinine clearance greater than or equal to 50 ml/min (uncorrected value), or
8.2. Isotope clearance measurement greater than or equal to 50 ml/min
9. No concurrent or recent (within four weeks) chemotherapy for the underlying haematological condition (excluding cyclophosphamide priming for stem cell harvest). This does not include thalidomide which is permitted
10. Although the bone marrow (BM) remission status is not important, patients must have cellularity greater than 20%
11. Patients must have sufficient stem cells in cryo-storage for two transplant procedures, this is in case graft failure occurs as a result of therapy
12. Patients must be negative for human anti-mouse antibodies (HAMA)
13. Written informed consent and the ability of the patient to co-operate with treatment and follow up must be ensured and documented
14. Female patients of child-bearing potential are eligible, provided they have a negative serum pregnancy test prior to enrolment and agree to use medically approved contraceptive precautions for four weeks prior to entering the trial, during the trial and for six months afterwards
15. Male patients must agree to use appropriate medically approved contraception during the trial and for six months afterwards
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
80
Participant exclusion criteria
1. Radiotherapy (except for localised pain control), endocrine therapy, immunotherapy or chemotherapy during the previous four weeks
2. All toxic manifestations of previous treatment must have resolved. Exceptions to this are alopecia or certain Grade one toxicities which in the opinion of the Investigator should not exclude the patient.
3. Patients with BM cellularity less than 20%
4. Patients who test positive for HAMA
5. Previous high dose therapy and autologous stem cell transplant
6. Patients in complete remission (CR) after chemotherapy and prior to autologous peripheral blood stem cell transplantation (APBSCT)
7. Pregnant and lactating women are excluded
8. Major thoracic and/or abdominal surgery in the preceding three to four weeks from which the patient has not yet recovered
9. Patients who are high medical risks because of non-malignant systemic disease, as well as those with active uncontrolled infection
10. Patients with any other condition that, in the Investigators opinion, would not make the patient a good candidate for the clinical trial
11. Patients known to be serologically positive for hepatitis B, C or human immunodeficiency virus (HIV)
12. History of allergy, in particular a history of allergy to rodents or rodent proteins
13. History of eczema and/or asthma
14. Concurrent congestive heart failure or prior history of New York Heart Association (NYHA) class III/ IV cardiac disease
15. Patients unable to provide informed consent or who are unable to co-operate for reasons of poor mental or physical health
16. Less than 4 x 10^6 CD34 positive cells per kg body weight
Recruitment start date
01/05/2007
Recruitment end date
17/12/2013
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Southampton General Hospital
Southampton
SO16 6YD
United Kingdom
Sponsor information
Organisation
Southampton University Hospitals NHS Trust (UK)
Sponsor details
Research and Development Office
Mailpoint 18
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom
+44 (0)2380 794 245
christine.mcgrath@suht.swest.nhs.uk
Sponsor type
Government
Website
Funders
Funder type
Charity
Funder name
Leukaemia Research Fund (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list