AL amyloidosis Nutritional, Metabolic, Endocrine Metabolic disorders
Conditions
Interventions
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.
Sponsors
University College London (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
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
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Clonal response 2. Toxicity and safety (including treatment-related mortality) 3. Recruitment rate and feasibility | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Acceptability of randomisations in each pathway 2. Quality of life questionnaire validity 3. Amyloidotic organ function | — |
Countries
United Kingdom
Outcome results
None listed