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

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-bortezomib-with-chemotherapy-for-amyloidosis-reveal

Contact information

Ms Milena Toncheva
Scientific

Trial Coordinator - Haematology Trials Group
Cancer Research UK & UCL Cancer Trials Centre
90 Tottenham Court Road
London
W1T 4TJ
United Kingdom

Email reveal@ctc.ucl.ac.uk

Study information

Study designMulticentre randomised interventional treatment trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleA pilot study of relapsed or refractory patients using Velcade™ (bortezomib) combination chemotherapy in AL amyloidosis
Study acronymREVEAL
Study objectivesThe 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) studiedTopic: National Cancer Research Network; Subtopic: Haematological Oncology; Disease: Leukaemia (acute), Leukaemia (acute lymphoblastic)
InterventionPAD 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 typeDrug
Pharmaceutical study type(s)
PhasePhase II
Drug / device / biological / vaccine name(s)Bortezomib, adriamycin, cyclophosphamide
Primary outcome measure1. 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 measures1. Improvement in amyloidotic organ function
2. Overall survival
3. Cost effectiveness
All assessed at 7 months.
Overall study start date01/12/2010
Completion date31/05/2013
Reason abandoned (if study stopped)Objectives no longer viable

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participantsPlanned sample size: 52; UK sample size: 52
Key inclusion criteria1. 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 criteria1. 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 enrolment01/12/2010
Date of final enrolment31/05/2013

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Cancer Research UK & UCL Cancer Trials Centre
London
W1T 4TJ
United Kingdom

Sponsor information

University College London (UCL) (UK)
University/education

Gower Street
London
WC1E 6BT
England
United Kingdom

Website http://www.ucl.ac.uk/
ROR logo "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 shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot 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