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

ISRCTN	ISRCTN34235460
DOI	https://doi.org/10.1186/ISRCTN34235460
Secondary identifying numbers	BRD/06/055

Submission date: 27/11/2006
Registration date: 26/01/2007
Last edited: 10/07/2017

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Julian Gillmore
Scientific

National Amyloidosis Centre
Royal Free & University College Medical School
Royal Free Hospital
London
NW3 2PF
United Kingdom

Phone	+44 (0)207 433 2726
Email	j.gillmore@medsch.ucl.ac.uk

Study information

Study design	Randomised multi-centre feasibility study
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
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
Study acronym	UKATT
Study objectives	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(s)	Not provided at time of registration – pending
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Phase III
Drug / device / biological / vaccine name(s)	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 study start date	31/01/2007
Completion date	31/01/2008

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	48
Key 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
Key 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
Date of first enrolment	31/01/2007
Date of final enrolment	31/01/2008

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

National Amyloidosis Centre

London
NW3 2PF
United Kingdom

Sponsor information

University College London (UK)
University/education

Joint UCLH and UCL Biomedical Research Unit
Ground Floor
Rosenheim Wing
25 Grafton Way
London
WC1E 5DB
England
United Kingdom

Phone	+44 (0)845 155 5000
Email	y.enever@medsch.ucl.ac.uk
Website	http://www.ucl.ac.uk/biomed-r-d
"ROR"	https://ror.org/02jx3x895

Funders

Funder type

Research organisation

Clinical Trials Advisory and Awards Committee (CTAAC) (UK) (ref: C23723/A7726)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Editorial Notes

10/07/2017: No publications found, verifying study status with principal investigator.