Contact information
Type
Scientific
Primary contact
Dr Julian Gillmore
ORCID ID
Contact details
National Amyloidosis Centre
Royal Free & University College Medical School
Royal Free Hospital
London
NW3 2PF
United Kingdom
+44 (0)207 433 2726
j.gillmore@medsch.ucl.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
BRD/06/055
Study information
Scientific title
A randomised, multi-centre trial to assess the feasibility of conducting a future phase III randomised trial in primary amyloidosis, comparing cyclophosphamide, thalidomide and dexamethasone with stem cell transplantation in patients with low risk of treatment related mortality and cyclophosphamide, thalidomide and dexamethasone with Mel-Dex in patients with high risk of treatment related mortality
Acronym
UKATT
Study hypothesis
This trial is intended to test the feasibility of a phase III study to address issues in patients with newly diagnosed primary (AL) amyloidosis at all stages of disease. The aim is to compare different chemotherapeutic regimens as an initial therapy with respect to rate of clonal response, safety and treatment related mortality and organ response.
In addition, quality of life before and after chemotherapy will be investigated to assess the validity of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30) and Multiple Myeloma (MY20) questionnaire in this patient population.
Ethics approval
Not provided at time of registration – pending
Study design
Randomised multi-centre feasibility 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 to request a patient information sheet
Condition
AL amyloidosis
Intervention
Patients will enter one of two treatment pathways (high or low intensity) on the basis of their disease and will be randomised within each pathway to one of two chemotherapy regimens on a 1:1 basis.
Patients entering the high intensity pathway will be randomised to Stem Cell Transplantation (SCT) or Cyclophosphamide, Thalidomide, Dexamethasone (CTD) and those randomised to the low intensity pathway will be randomised to receive either CTD or Melphalan and Dexamethasone (Mel Dex).
Intervention type
Drug
Phase
Phase III
Drug names
Cyclophosphamide, thalidomide, dexamethasone, melphalan
Primary outcome measure
1. Clonal response
2. Toxicity and safety (including treatment-related mortality)
3. Recruitment rate and feasibility
Secondary outcome measures
1. Acceptability of randomisations in each pathway
2. Quality of life questionnaire validity
3. Amyloidotic organ function
Overall trial start date
31/01/2007
Overall trial end date
31/01/2008
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Aged 18 years or greater
2. Newly diagnosed as having systemic AL amyloidosis who have:
2.1. Diagnostic Congo red histology confirming amyloid deposits
2.2. Immunohistochemical exclusion of Systemic (AA) and Transthyretin (TTR) amyloidosis
2.3. Exclusion of genetic mutations associated with hereditary amyloidosis whenever doubt about the diagnosis exists, according to Network Advisory Committee (NAC) current practice
2.4. 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 more than or equal to 100 mg/l associated with an abnormal kappa/lambda ratio
2.5. Amyloid-related organ dysfunction or organ syndrome
3. Capable of providing written, informed consent
4. Estimated life expectancy of at least six months
5. Prepared to use contraception in accordance with (and consent to) the Pharmion Risk Management Programme
6. Women of Child-Bearing Potential (WCBP) must agree to use TWO methods of contraception beginning two weeks prior to the start of thalidomide, while on thalidomide and four 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
7. Male patients (including those who have had a vasectomy) must use condoms when engaging in heterosexual activity with WCBP while on thalidomide and four weeks after the last dose of thalidomide, as outlined in the Pharmion Risk Management Programme
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
48
Participant exclusion criteria
1. Overt symptomatic multiple myeloma
2. Bone marrow plasmacytosis more than 10%
3. Underlying Immunoglobulin M (IgM) paraproteinaemia
4. Amyloidosis of unknown or non AL type
5. 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)
6. Trivial or incidental AL amyloid deposits in the absence of a significant amyloid related organ syndrome (e.g., isolated carpal tunnel syndrome)
7. Isolated soft tissue involvement
8. Severe peripheral neuropathy causing significant functional impairment
9. New York Heart Association (NYHA) class IV heart failure
10. Liver involvement by amyloid causing bilirubin more than 1.5 times upper limit of normal
11. Previous treatment for systemic AL amyloidosis
12. Previous or concurrent active malignancies, except surgically removed basal cell carcinoma of the skin or other in situ carcinomas
13. Pregnant, lactating or unwilling to use adequate contraception
14. Intolerance/sensitivity to any of the study drugs
Recruitment start date
31/01/2007
Recruitment end date
31/01/2008
Locations
Countries of recruitment
United Kingdom
Trial participating centre
National Amyloidosis Centre
London
NW3 2PF
United Kingdom
Sponsor information
Organisation
University College London (UK)
Sponsor details
Joint UCLH and UCL Biomedical Research Unit
Ground Floor
Rosenheim Wing
25 Grafton Way
London
WC1E 5DB
United Kingdom
+44 (0)845 155 5000
y.enever@medsch.ucl.ac.uk
Sponsor type
University/education
Website
Funders
Funder type
Research organisation
Funder name
Clinical Trials Advisory and Awards Committee (CTAAC) (UK) (ref: C23723/A7726)
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