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

Phase 3

Completed

• Conditions: AL amyloidosis; Nutritional, Metabolic, Endocrine; Metabolic disorders

• Registration Number: ISRCTN34235460
• Lead Sponsor: niversity College London (UK)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-01-26
• Last Update Posted: 21 August 2017

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 48

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

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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1. Clonal response<br>2. Toxicity and safety (including treatment-related mortality)<br>3. Recruitment rate and feasibility

Secondary Outcome Measures

Name	Time	Method
1. Acceptability of randomisations in each pathway <br>2. Quality of life questionnaire validity <br>3. Amyloidotic organ function