Clinical Trials
NCRI Myeloma Clinical Trials Committee Report
Preliminary results from MM IX on responses were presented at ASH 2007 and it is hoped that outcome data will be presented later in 2009.
The Myeloma CTC meets on a regular basis to take forward the design and approval of clinical studies. The group has worked to develop the UKMFÕs role within the National Cancer Research Institute Myeloma Clinical Trials Committee (NCRI Myeloma CTC) resulting in the integration of the NCRI and UKMF Myeloma CTCs enhancing the working relationship between the two groups. Discussions with CTAAC re trial design and funding earlier in the year were enlightening and constructive in identifying mutual areas of concern that should help secure funding for trials in the future.
The CTC has agreed a strategy to promote, support and develop a rolling programme of trials over the next 3 years to develop a portfolio of a phase III de novo trial and a randomised, phase II, relapsed intensive and non-intensive study. It is also supporting the development of a smaller phase II randomised trial to address the role of early versus late autologous stem cell transplantation in the era of novel therapies with the view of utilising the data to inform a later phase III trial. Support is also being given to devise studies in both de novo and relapsed Amyloidosis incollaboration with the National Amyloidosis Centre and WaldenstromÕs Macroglobulinaemia in collaboration with the NCRI Lymphoma CTC. In addition it is promoting studies examining supportive care and quality of life studies.
The Intensive Relapse Study Group has worked with the Committee to secure funding from the CTAAC for a phase 3 study, Myeloma X (Intensive), that opened in Spring 2008. A new de novo study, to replace the highly successful Myeloma IX trial that closed in November 2007, is awaiting final funding approval from CTAAC. It is hoped this will be successful and it is anticipated that the trial will open by the 3rd quarter of 2009.
Current and recent UK myeloma trials
Study
|
Title
|
PI
|
Status
|
Myeloma XI
|
This is a pragmatic, randomised,
phase III, multi−centre, parallel group design, open labelled trial comparing thalidomide, lenalidomide and bortezomib combinations and maintenance lenalidomide in newly diagnosed patients with symptomatic
myeloma.
|
Prof Gareth
Morgan
|
Open
|
Myeloma X -
Intensive
|
A randomized controlled trial for post autologous stem cell
transplantation relapsed myeloma patients suitable for a second autograft; to assess the response rate to PAD in patients
relapsing with MM following a previous autograft and to assess the overall response rate and survival following high-dose
chemotherapy (with autograft) compared with
low-dose consolidation.
|
Prof Gordon Cook
|
Open
|
MUK One
|
A randomised, parallel group, phase
II selection trial in patients with relapsed or refractory multiple myeloma to determine the optimal dosing regimen when bendamustine is combined with thalidomide and dexamethasone in relapsed/refractory
myeloma.
|
Prof Steve Schey
|
Open
|
MMIFTT
|
This trial is looking
at DNA vaccine therapy after a stem cell transplant to help treat people with
myeloma.
|
Prof C. Ottensmeier
|
Open
|
Radiolabelled
MAB pre-autograft
|
This trial is looking
at a radiolabelled monoclonal antibody for people with myeloma who are going
to have high dose chemotherapy, followed by autograft.
|
Dr Kim Orchard
|
Open
|
Myeloma IX
|
A randomized
controlled trial of VAD versus CTD chemotherapy in de novo myeloma patients
plus comparison of oral clodronate and iv zoledronic acid
|
Prof Gareth
Morgan and Tony Childs
|
Closed
|
MERIT
|
MyEloma Renal Impairment Trial – a randomized trial of
adjunctive plasma exchange in de novo myeloma with acute renal failiure.
|
Dr Judith
Behrens
|
Closed
|
UKATT/ UK Amyloidosis Treatment Trial
|
A randomised, multicentre feasibility trial in AL
Amyloidosis, comparing CTD with SCT in patients with low risk of Treatment
Related Mortality and CTD with Mel-Dex in patients
in whom SCT would not be considered appropriate as first line therapy
http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=2318
|
Dr Julian
Gilmore
|
Closed
|
Advanced myeloma quality of life study
|
This study is looking at how people cope with the effects of
myeloma and treatment to see if their health care teams can do more to help.
|
Dr John Snowden
|
Closed
|
Palifermin study
|
This study is looking at when to
give palifermin to treat painful sores in the mouth after high dose melphalan chemotherapy for myeloma.
|
Dr Charles Brigden
|
Closed
|
Myeloma XI
This is a pragmatic, randomised, phase
III, multi−centre, parallel group design, open labelled trial comparing thalidomide, lenalidomide and bortezomib combinations and maintenance lenalidomide in newly diagnosed patients with symptomatic myeloma. An intensive treatment
pathway will be followed by younger/fitter patients where intensive HDT with
stem cell support is considered appropriate, whilst older/less fit patients
will proceed through the non−intensive pathway. Both pathways comprise
induction, consolidation and maintenance components. The recruitment target
requires that approximately 492 patients are recruited per year over a 4 year
period.
The trial aims to answer three main questions: at induction, consolidation and maintenance:-
1. Is cyclophosphamide-lenalidomide-dexamethasone
(RCD) given to maximum response, a better induction regimen than the current UK
gold standard of cyclophosphamide-thalidomide-dexamethasone (CTD)?
2. For patients achieving a sub optimal response to induction across both
treatment pathways (<VGPR), can the use of bortezomib,
cyclophosphamide and dexamethasone (VCD) improve responses and does this
translate into improved PFS and OS?
3. Can lenalidomide at maintenance improve PFS and OS
when compared to the use of no maintenance?
http://www.controlled-trials.com/ISRCTN49407852/myeloma+XI
Trial Status: Set up
Chief investigator
Prof Gareth Morgan, Royal Marsden Hospital
Trial Contact
Louise Flanagan,
Senior Clinical Trial Co-ordinator
Document Downloads
Trial Summary PDF
Site Feasibility Questionnaire
Source
- http://ctru.leeds.ac.uk/myelomaXI
Myeloma X Relapse
(Intensive)
The primary objective is to determine the
effect on freedom-from disease progression of a second autologous stem cell
transplant (ASCT) compared with low-dose consolidation following re-induction
therapy.
The secondary objectives of this study are: to
assess the response rate to PAD in patients relapsing with MM following a
previous autograft; to assess the overall response
rate and survival following high-dose chemotherapy (with autologous stem cells)
compared with low-dose consolidation; to determine the overall survival; to
determine the safety and toxicity of a second ASCT; to assess safety and
toxicity of PAD therapy; to assess whether type of PBSC mobilisation and harvest is prognostic of time to disease progression; to assess the
feasibility of stem cell collection at relapse from a prior ASCT following
re-induction and to determine the impact of the treatment strategies on pain QoL.
Population: Patients with symptomatic
(including non-secretory) myeloma previously treated with standard chemotherapy
and ASCT that require therapy for first progressive disease at ≥18 months from
time of first transplant will be eligible for inclusion.
Intervention: All patients will receive
re-induction therapy with 2 4 cycles of PAD (bortezomib,
doxorubicin and dexamethasone), following which peripheral blood stem cells
(PBSC) will be mobilised and harvested. Mobilisation and harvest is optional in patients who have
sufficient stem cells stored from a previous harvest, but is encouraged in all
patients. Those patients who successfully complete the re-induction stage and mobilisation (including those who do not mobilise but have stored PBSC from prior mobilisations) will be randomised and assigned to either high-dose melphalan and PBSC
rescue, or low-dose cyclophosphamide-weekly.
Target number of participants: 320 patients
are required at randomisation, and it is anticipated
that approximately 460 patients will need to be registered to achieve this.
Trial Summary
Registration of interest and feasibility
questionnaire
Trial Status: Recruitment
Chief Investigator: Dr Gordon Cook, Leeds
Teaching Hospitals NHS Trust
Trial contact:
Suzanne Hartley , Senior Trial Manager
Tel : 0113 343 8041
Email : s.hartley@leeds.ac.uk
Source
- http://ctru.leeds.ac.uk/myelomaXrelapse
Myeloma IX
Trial Status: Closed. The relapse sub-protocol remains open to
patients already randomised into the trial.
Study aim: To compare 2nd and 3rd generation
bisphosphonates, induction chemotherapy regimens and thalidomide maintenance in
newly diagnosed multiple myeloma patients of all ages.
Study design: A phase III randomised open factorial trial, comprising an Intensive Pathway for younger/fitter
patients where intensive high dose treatment with stem cell support is
considered appropriate, and a Non-Intensive Pathway for older/less fit patients
where standard dosed chemotherapy is considered appropriate.
Younger/fitter patients will be randomised to receive i) clodronate versus zoledronic acid, ii) CVAD versus CTD (both followed by high-dose melphalan and autograft) and iii) thalidomide maintenance
versus no thalidomide. Younger/fitter patients with a tissue-compatible sibling
will also be offered a mini-allogeneic transplant.
Older/less fit patients will be randomised to receive i) clodronate versus zoledronic acid, ii) MP versus CTDa and iii) thalidomide
maintenance versus no thalidomide.
In optional sub-protocols, patients may be
offered BD if they do not respond to induction chemotherapy, or at first
relapse.
Objectives:
Primary – Intensive pathway
• To compare two induction regimens, CVAD (infusional) v CTD (oral)
• To assess low-intensity conditioning (LIC)
allogeneic stem cell transplantation (‘mini-allograft’) following high-dose melphalan plus autograft in
patients with donors available.
• To assess the response to BD in patients not
responding to the randomised induction therapy.
Primary – Non-intensive pathway
• To compare two induction/consolidation
regimens, MP v CTD attenuated (CTDa)
Secondary (both pathways)
• To compare two bisphosphonates, sodium clodronate (2nd generation) v zoledronic acid (3rd generation)
• To assess the value of giving low-dose
thalidomide in maintenance (versus no treatment)
• To investigate quality of life in the
short-term (during induction chemotherapy/bisphosphonate treatment) and in the
long-term (during maintenance therapy)
• To determine the relevance of
genetic/cytogenetic changes and define risk groups
• To determine the relevance of immunophenotypic changes and molecular evidence of residual
disease
• To evaluate serum free light chain (flc) measurement as a prognostic factor and in monitoring
disease
• To determine the relevance of biochemical
markers of bone metabolism in monitoring disease.
• To determine the effect of cytogenetic group
and prior treatment regimen on progression-free survival and response rate to
BD at first relapse.
Endpoints:
Primary
• Overall survival
• Progression-free survival
• Response
Secondary
• Quality of life
• Skeletal-related events (bone fractures,
radiation to bone, surgery to bone, spinal cord compression)
• Height loss
• Toxicity (thromboembolic events, renal
toxicity, haematologic toxicity, graft versus host
disease (GvHD))
• Proportion receiving BD as ‘early rescue’ on
induction chemotherapy
• Proportion receiving BD at relapse
Number of centres:
141 (UK)
Number of patients:
Pathway Target Actual
Intensive Pathway 1080 1114
Non-Intensive Pathway 850 856
Maintenance 762 820
Useful links:
ISRCTN: http://www.controlled-trials.com/ISRCTN68454111/68454111
NIHR CRN Clinical Research Portfolio:
http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=1176
Key: C: cyclophosphamide; T: thalidomide; D:
dexamethasone; V: vincristine; A: Adriamycin; M: melphalan;
P: prednisolone; B: bortezomib
Chief Investigators:
Professor JA Child (University of Leeds)
Professor GJ Morgan (Royal Marsden Hospital,
London)
Professor GH Jackson (Freeman Hospital,
Newcastle)
Trial Contact:
Phil Best
Tel: 0113 343 8392
Email: p.best@leeds.ac.uk
Source
- http://ctru.leeds.ac.uk/myelomaIX
MUK One
ObjectivesThe primary aim is to determine the optimal dosing regimen when bendamustine is combined with thalidomide and dexamethasone in relapsed/refractory myeloma.
Primary endpoints: Partial response or better; tolerability; and
progression free survival.
Secondary endpoints: Maximum response rate and overall response
rate; response duration; time to next treatment; safety and toxicity;
proportion of patients successfully receiving six cycles of treatment with no
dose reductions or delays; feasibility of stem cell harvest following
treatment; overall survival.
Study Design (methodology)
This is a
multi-centre, randomised, parallel group, phase II selection trial in patients with relapsed or
refractory multiple myeloma (first relapse or later). Patients will be stratified
according to whether they are refractory, or relapsed and responsive, presence
or absence of renal or haematological impairment and
number of previous treatments.
This is a two-stage design to assess tolerability and efficacy
simultaneously. The trial may be terminated at the end of the first stage due
to lack of efficacy or unacceptable tolerability. Assuming at least one of the
schedules successfully passes the first stage, a schedule will be deemed worthy
of further consideration in a phase III trial at the end of stage two if it is
a) acceptably tolerable AND b) sufficiently efficacious. If both treatment
schedules successfully pass stage two, initial selection criteria will be based
on progression-free survival rates. Assuming tolerance, and in the absence of
disease progression, the treatment phase will continue for a minimum of six
cycles or until best response plus 2 cycles, up to a maximum of 9 cycles.
After completion of bendamustine,
thalidomide and dexamethasone (BTD), the patient may be assessed for
eligibility for PBSC mobilisation and harvest and
future ASCT. If eligible, they may undergo stem cell harvest at the discretion
of the local investigator. Data will be collected to assess the adequacy of the
harvest. If there is adequate stem cell harvest, cells will be stored and may
be used for ASCT at disease progression, at the discretion of the investigator.
If the patient is not considered by the investigator to be suitable for PBSC
harvest, they will proceed to long term follow up.
Follow up will be every 4 weeks until initiation of a new
treatment for disease progression, death, or until the end of the trial’s
follow up period,(1 year post last patient recruited) whichever occurs
first. After initiation of a new treatment, trial follow up will be for
survival only.
Number of Participants:
A maximum of 98
participants are required.
Links
http://www.controlled-trials.com/ISRCTN90889843
http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=9454
Status: Open
Chief Investigator: Professor Steve Schey - King's College Hospital
Trial Contact: Louise Flanagan, Senior Trial Manager
Source - http://ctru.leeds.ac.uk/MUKOne
MERIT
Study aim: To determine whether the addition
of plasma exchange to chemotherapy increases the likelihood of renal recovery
(dialysis-independent at 100 days) in patients with acute renal failure
associated with newly diagnosed myeloma.
Study design: A multi-centre, open, phase III randomised controlled trial. Patients will be randomised to receive plasma exchange or not (in addition to chemotherapy of the local
treating clinicians’ choice) in the first two weeks from trial entry.
Objectives:
Primary
• To determine whether the addition of plasma
exchange to dexamethasone and cytotoxic chemotherapy increases the likelihood
of renal recovery (dialysis-dependent at 100 days) in patients with acute renal
failure and newly-diagnosed myeloma.
Secondary
• To determine whether addition of plasma
exchange to dexamethasone and cytotoxic chemotherapy affects overall survival
• To assess the impact of the addition of
plasma exchange to intensive chemotherapy on patients’ quality of life
• To assess the value of renal histology in
predicting recovery of renal function
• To assess the value of serum free light
chain assay in determining response of the myeloma to chemotherapy and recovery
of renal function in patients with renal failure.
Endpoints:
Primary
• Proportion of patients alive and
dialysis-independent at 100 days.
Secondary
• Overall survival
• Proportion of patients alive and
dialysis-independent at 6 and 12 months
• GFR (calculated or measured) at 15 days, 100
days, 6 months and 12 months
• Change in serum free light chain levels
between days 0 and 15
• Response of myeloma to treatment according
to standard criteria at 100 days, 6 months and 12 months
• Quality of life.
Number of centres:
22 (UK)
Number of patients:
Target Actual
286 79
Useful links:
ISRCTN:
http://www.controlled-trials.com/ISRCTN37161699/merit
NIHR CRN Clinical Research Portfolio:
http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=1179
Trial Status: Closed
Chief Investigator: Dr G Gaskin (Hammersmith
Hospital, London), Dr J Behrens (Epsom and St Helier Hospital)
Trial Contact:
Dr Sue Bell
Tel: 0113 343 1492
Email: s.e.bell@leeds.ac.uk
Source
- http://ctru.leeds.ac.uk/merit
A trial looking at DNA vaccine therapy after stem cell transplant for myeloma (MMIFTT)
This trial is looking at DNA vaccine
therapy after a stem cell transplant to help treat people with myeloma.
Myeloma is a type of cancer that develops
from cells in the bone marrow called plasma cells. Most patients will have chemotherapy for myeloma and this can get the cancer under
control (remission). But the cancer is likely to come back
(relapse) or become more active over time.
Some patients have a stem marrow transplant using their own stem cells.
This is called an ‘autologous’ transplant. But even a transplant may
not work in all patients and sometimes the cancer may come back.
This trial is looking into using a DNA
vaccine, which is made from a sample of the patient’s cancer cells. The
patients will have this vaccine as injections after their transplant. The
researchers hope that the vaccine will increase the body’s ability to fight
cancer if it comes back. The aim of this trial is to find out if
·
It is possible to make the DNA vaccine and to vaccinate patients
·
The patient’s immune system can recognise and kill the cancer cells
Recruitment
Start
01/03/2004
End
31/12/2011
Phase
Phase
1/2
A study to find out how people with advanced myeloma cope with symptoms and treatment
Please note this trial is no longer
recruiting patients.
This study is looking at how people cope
with the effects of myeloma and treatment to see if their health
care teams can do more to help.
Myeloma symptoms include bone pain, tiredness, sickness
and shortness of breath. This can affect people’s quality of life. Doctors can control symptoms with treatment. But sometimes treatments have side
effects that may cause further problems in the long term. Doctors don’t want to
give treatments that do more harm than good.
The aims of this study are to find out
·
How people cope physically and psychologically with advanced
myeloma
·
How satisfied people feel with their care and if there are any
unmet care needs
·
More about side effects of myeloma symptom treatment
The researchers will collect information
to see if they can improve quality of life for people with advanced myeloma in
the future.
Please note, you cannot volunteer for
this study. A member of your care team may ask if you would like to join the
study.
Recruitment
Start
22/05/2008
End
31/10/2010
Phase
Other
Source - http://cancerhelp.cancerresearchuk.org/trials/a-study-to-find-out-how-people-with-advanced-myeloma-cope-with-symptoms-and-treatment
A trial looking at having a radiolabelled monoclonal antibody before an autologous stem cell transplant for myeloma
This trial is looking at a radiolabelled monoclonal antibody for people with myeloma who are going to have high dose chemotherapy, followed by treatment with their own blood stem cells (autologous stem cell transplant).
Doctors often treat myeloma with high dose chemotherapy and a stem cell transplant. Some people also have radiotherapy. But high doses of drugs and radiotherapy can cause damage to normal cells as well as cancer cells.
Researchers are looking at ways of targeting treatment, so that it reaches the cancer cells but causes less damage to healthy tissue. In this trial, they are looking at a type of biological therapy called a monoclonal antibody (MAB).
The monoclonal antibody is radiolabelled. This means it has a radioactive molecule attached to it. The antibody targets a particular protein on the surface of myeloma cells, and then the radioactivity kills the cells.
The aims of this trial are to
· Find out if this radiolabelled MAB helps people who are having a stem cell transplant for myeloma
· Learn more about the side effects
Recruitment
Start
18/12/2007
End
17/12/2013
Phase
Phase
2
Kim Orchard, Soton
Source - http://cancerhelp.cancerresearchuk.org/trials/a-trial-looking-at-having-a-radio-labelled-monoclonal-antibody-before-an-autologous-stem-cell-transplant-for-myeloma
A study looking at the drug palifermin in people having chemotherapy and stem cell transplant for myeloma (20050219)
Please note this trial is no longer
recruiting patients.
This study is looking at when to give palifermin to treat painful sores in the mouth after high dose melphalan chemotherapy for myeloma.
Doctors sometimes treat myeloma with high
dose chemotherapy, followed by a stem cell transplant. This high dose of chemotherapy
can often give you a very sore mouth (mucositis). A sore mouth can stop you from being able to swallow
or eat.
You may also be more likely to get mouth infections if you have mucositis.
So it is important that it is treated as soon as possible.
There is a drug called palifermin (Kepivance) which
doctors already use to treat mucositis. Palifermin is a protein called ‘keratinocyte growth factor’
(KGF). KGF encourages the cells lining your mouth and digestive system to grow.
People having intensive treatment for myeloma may already have this drug before
and after their chemotherapy and transplant. But researchers want to find out
more about whether palifermin works just as well if
you only have it before chemotherapy and transplant.
The aims of this study are to see if palifermin
·
Stops you having as painful mouth sores as those who don’t have palifermin
·
Causes or worsens cloudiness on the eye’s lens (cataracts) - the research team do not
believe that palifermin will cause or worsen
cataracts
Recruitment
Start
28/12/2006
End
07/07/2009
Phase
Phase
3
UKATT/ UK Amyloidosis Treatment Trial
A randomised, multicentre feasibility trial in AL Amyloidosis, comparing CTD with SCT in patients with low risk of Treatment Related Mortality and CTD with Mel-Dex in patients in whom SCT would not be considered appropriate as first line therapy
Topic Cancer
Portfolio Eligibility Funded by UKCRC partner
ISRCTN 34235460
EudraCT 2006-006395-37
MREC N° 07/Q0401/47
UKCRN ID 2318
Phase Pilot/Feasibility
WHO ID
Research Summary
A randomised, multicentre feasibility trial in AL Amyloidosis, comparing CTD with SCT in patients with low risk of Treatment Related Mortality and CTD with Mel-Dex in patients in whom SCT would not be considered appropriate as first line therapy.
Study Type Interventional
Design Type Treatment
Disease(s) Multiple Sites
Current Status Closed - follow-up complete
Closure Date 20/03/2009
Global Sample Size 48
Global Recruitment to Date 56%
Geographical Scope UK Multi-Centre
Lead Country England (also active in Scotland)
Main Inclusion Criteria
•Aged 18
years or greater
•Newly diagnosed as having systemic AL amyloidosis who have:
-Diagnostic Congo red histology confirming amyloid deposits
-Immunohistochemical exclusion of AA and TTR amyloidosis
-Exclusion of genetic mutations associated with hereditary amyloidosis whenever
doubt about the diagnosis exists, according to NAC current practice
-Underlying plasma cell dyscrasia that can be identified and monitored by
Freelite serum free light chain assay as follows: absolute serum free light
chain concentration = 100mg/l associated with an abnormal kappa/lambda ratio.
Among patients with a creatinine clearance of <50mls/min, inclusion
requires the kappa/lambda ratio to be either <0.22 or >3.3
-Amyloid related organ dysfunction or organ syndrome
•Capable of providing written, informed consent
•Estimated life expectancy of at least 6 months
•Prepared to use contraception in accordance with (and consent to) the
Pharmion Risk Management Programme
-Women of childbearing potential (WCBP) (See Appendix H) must agree to use
TWO methods of contraception beginning 2 weeks prior to the start of
thalidomide, while on thalidomide and 4 weeks after the last dose of
thalidomide. The two methods of contraception must include one highly
effective method and one additional effective (barrier) method, as outlined
in the Pharmion Risk Management Programme.
-Male patients (including those who have had a vasectomy) must use condoms
when engaging in heterosexual activity with WCBP while on thalidomide and 4
weeks after the last dose of thalidomide, as outlined in the Pharmion Risk
Management Programme.
Main Exclusion Criteria
•Overt
symptomatic multiple myeloma
•Bone marrow plasmacytosis >10%
•Underlying IgM paraproteinaemia
•Amyloidosis of unknown or non AL type
•Localised AL amyloidosis (in which amyloid deposits are limited to a typical
single organ, for example the bladder or larynx, in association with a clonal
proliferative disorder within that organ
•Trivial or incidental AL amyloid deposits in the absence of a significant
amyloid related organ syndrome (e.g., isolated carpal tunnel syndrome)
•Isolated soft tissue involvement
•Severe peripheral neuropathy causing significant functional impairment
•NYHA Class IV heart failure
•Liver involvement by amyloid causing bilirubin >1.5 times upper limit of
normal
•Previous treatment for systemic AL amyloidosis
•Previous or concurrent active malignancies, except surgically removed basal
cell carcinoma of the skin or other in situ carcinomas
•Pregnant, lactating or unwilling to use adequate contraception
•Intolerance / sensitivity to any of the study drugs
Chief
Investigator(s)
Dr Julian
Gillmore
Further details, please contact Ms Gillian Eddison
CTRU
17
Springfield Mount
Leeds
West
Yorkshire
LS2 9NG
UNITED
KINGDOM
Tel: 0113
3438391
g.eddison@leeds.ac.uk
Funder(s) Cancer Research UK
Sponsor(s) University College London
Source - http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=2318