Velcade™ (bortezomib) combination chemotherapy in AL amyloidosis
| ISRCTN | ISRCTN33283585 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN33283585 |
| EudraCT/CTIS number | 2009-014906-33 |
| Secondary identifying numbers | 8441 |
- Submission date
- 30/07/2010
- Registration date
- 30/07/2010
- Last edited
- 27/03/2019
- Recruitment status
- Stopped
- Overall study status
- Stopped
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Contact information
Ms Milena Toncheva
Scientific
Scientific
Trial Coordinator - Haematology Trials Group
Cancer Research UK & UCL Cancer Trials Centre
90 Tottenham Court Road
London
W1T 4TJ
United Kingdom
| reveal@ctc.ucl.ac.uk |
Study information
| Study design | Multicentre randomised interventional treatment trial |
|---|---|
| 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 below to request a patient information sheet |
| Scientific title | A pilot study of relapsed or refractory patients using Velcade™ (bortezomib) combination chemotherapy in AL amyloidosis |
| Study acronym | REVEAL |
| Study objectives | The trial aims to assess the efficacy, safety and tolerability of two bortezomib-based combination chemotherapy regimens in patients with AL amyloidosis who have relapsed (disease has been succesfully treated but has returned) or have inadequate response to front line treatment (disease has responded partly but not enough to improve the amyloid related organ function) or are refractory (disease has not responded at all to prior treatment). Background: AL amyloidosis is a multisystem disorder resulting from the accumulation of abnormal protein deposits called amyloid deposits in various organs of the body, causing impairment of organ function. The deposited proteins are formed by light chains secreted by abnormal plasma cells (a type of blood cell). Treatment of AL amyloidosis involves chemotherapy to kill the abnormal plasma cell, thus reducing the abnormal light chains, in the hope of slowing down or halting amyloid deposition, and preserving organ function. Bortezomib, used as a single agent, has been shown to be an effective agent for treating myeloma and amyloidosis and combining it with other drugs appears to increase the rapidity and completeness of response i.e. a quick and long-lasting remission in myeloma. The current study would be the first study of such combinations in relapsed or refractory AL amyloidosis. Specific aims of research: The study will compare two bortezomib-dexamethasone-chemotherapy combinations, one with adriamycin (PAD) and one with cyclophosphamide (CVD), in a randomised multicentre parallel phase II design. Outline of research plan: The patients will be identified and consented at the UK National Amyloidosis Centre and will be treated at regional haematology centres (RHCs). They will be given 3 cycles of chemotherapy and will be assessed for response thereafter. Those who have only a partial response will continue to a maximum of six cycles. |
| Ethics approval(s) | Central London REC 4 pending as of 13/08/2010, ref: 10/H0715/30 |
| Health condition(s) or problem(s) studied | Topic: National Cancer Research Network; Subtopic: Haematological Oncology; Disease: Leukaemia (acute), Leukaemia (acute lymphoblastic) |
| Intervention | PAD or CVD (maximum of 6 x 21 day cycles): 1. PAD: Bortezomib 1.0 mg/m2 intravenous (IV) Days 1, 4, 8, 11 (increase to 1.3 mg/m2 if well tolerated) Doxorubicin 18 mg/m2 IV Days 1, 8 Dexamethasone 20 mg orally (po) Days 1, 4, 8, 11 (increase to 40 mg if well tolerated) 2. CVD: Bortezomib 1.0 mg/m2 IV Days 1, 4, 8, 11 (increase to 1.3 mg/m2 if well tolerated) Cyclophosphamide 350 mg/m2 po Days 1, 8, 15 Dexamethasone 20 mg po Days 1, 4, 8, 11 (increase to 40 mg if well tolerated) Follow-up length: 7 months Study entry: single randomisation only |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Bortezomib, adriamycin, cyclophosphamide |
| Primary outcome measure | 1. Clonal response of the underlying plasma cell dyscrasia 2. Safety and toxicity of PAD and CVD All assessed at 3 or 7 months. |
| Secondary outcome measures | 1. Improvement in amyloidotic organ function 2. Overall survival 3. Cost effectiveness All assessed at 7 months. |
| Overall study start date | 01/12/2010 |
| Completion date | 31/05/2013 |
| Reason abandoned (if study stopped) | Objectives no longer viable |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned sample size: 52; UK sample size: 52 |
| Key inclusion criteria | 1. Aged 18 years or greater, either sex 2. Systemic AL amyloidosis who fulfil all the following criteria: 2.1. Measurable clonal disease in the serum as defined by either a serum paraprotein of greater than 7 g/L or the abnormal component of the serum free light chain greater than 75 mg/L (abnormal ratio only in case of renal failure) 2.2. Amyloid related organ dysfunction or organ syndrome 3. Following prior chemotherapy or prior autologous stem cell transplant, evidence of either: 3.1. Clonal disease relapse 3.2. Refractory clonal disease 3.3. Inadequate clonal response (defined as less than a 90% reduction in serum clonal markers) 4. Capable of providing written informed consent |
| Key exclusion criteria | 1. Overt symptomatic non-amyloid manifestations of multiple myeloma 2. Amyloidosis of unknown or non-AL type 3. 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) 4. Trivial or incidental AL amyloid deposits in the absence of a significant amyloid related organ syndrome (e.g., isolated carpal tunnel syndrome) 5. Allogeneic stem cell transplantation 6. Solid organ transplantation 7. Severe peripheral neuropathy or autonomic neuropathy causing significant functional impairment 8. Thrombocytopaenia (platelet count less than 50 x 10^9/l) 9. Neutropaenia (neutrophil count less than 1 x 10^9/l) 10. Liver involvement by amyloid causing bilirubin greater than 2 times or alkaline phosphatase greater than 4 times upper limit of normal 11. Estimated glomerular filtration rate (eGFR) less than 20 ml/min but not on dialysis (patients on dialysis are not excluded) 12. Ejection fraction less than 40% 13. New York Heart Association (NYHA) class IV heart failure 14. Eastern Cooperative Oncology Group (ECOG) performance status greater than 3 15. Estimated life expectancy of less than 3 months 16. Active hepatitis B or C or human immunodeficiency virus (HIV) infection 17. Previous cumulative anthracycline dose of greater than 200 mg/m2 18. Previous treatment with bortezomib combined with anthracycline and/or alkylator and/or immunomodulatory drugs (ImiD) 19. Concurrent active malignancies, except surgically removed basal cell carcinoma of the skin or other in situ carcinomas 20. Pregnant, lactating or unwilling to use adequate contraception 21. Intolerance/sensitivity to any of the study drugs |
| Date of first enrolment | 01/12/2010 |
| Date of final enrolment | 31/05/2013 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Cancer Research UK & UCL Cancer Trials Centre
London
W1T 4TJ
United Kingdom
W1T 4TJ
United Kingdom
Sponsor information
University College London (UCL) (UK)
University/education
University/education
Gower Street
London
WC1E 6BT
England
United Kingdom
| Website | http://www.ucl.ac.uk/ |
|---|---|
"ROR" |
https://ror.org/02jx3x895 |
Funders
Funder type
Charity
Cancer Research UK (CRUK) (UK) - Clinical Trials Advisory and Awards Committee (CTAAC) grant (ref: C23725/A11440)
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 |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
27/03/2019: Internal review
11/05/2018: Trial status changed to stopped. https://www.ncbi.nlm.nih.gov/pubmed/28984490 confirms that REVEAL study was stopped in 2014.
01/03/2016: No publications found, verifying study status with principal investigator
