CML
Research for better treatment
Steve O’Brien
Northern Institute for Cancer Research
Newcastle University Medical School
CML patient meeting, 11th October 2014
Clinical trials
Phase I studies designed to find out the most effective dose of the
drug and the possible side effects of the drug.
Phase II studies carried out on different cancers so that the
research team can find out how active a particular drug is. Only
about 20 to 30 patients with each cancer.
Phase III studies to compare a new treatment with the best
treatment currently available.
Phase III trials are usually randomised and may include a double
blind procedure.
Others include – Sample banking; Epidemiological and phase IV
long term safety monitoring usually post approval
csg.ncri.org.uk/groups-list/
CML trials in the UK
Destiny
low level disease (MMR)
reduce then stop if possible
pilot study
CHOICES
SPIRIT trials
Around the world
Germany – nilotinib
France – interferon alpha
US – dasatinib, early response
India – efficacy of generics
Thank you…
Acknowledgements
Data analysis and presentation
Stephen O’Brien, Corinne Hedgley, Sarah Adams, Paul Terril, John McCullough
Trial management and
data collection, Newcastle
Corinne Hedgley, Lynn Seeley, Caroline Hodgson, Ruth Bescoby, Carrie Page,
Angela Fallows, Laura Brown, Gemma Gills, Wendy Banks, Meg Buckley, Leanne
Woolmer, Wendy Osborne
PCR & DNA/RNA biobanking
Letizia Foroni, Gareth Gerrard, Hammersmith
Cell biobanking
Tessa Holyoake, Alan Hair, Glasgow
Study Management Committee
SO’B, CH, Richard Clark, Liverpool; Jane Apperley, Hammersmith, Mhairi
Copeland (Chair of CML WG)
Data Monitoring Committee
John Goldman, Keith Wheatley, Graham Dark, Charles Schiffer
Sponsor
Newcastle Hospitals NHS Foundation Trust
Funder
Bristol Myers Squibb: Glenn Kroog, Milayna Subar, Sonal Chavda-Sitaram
Chief Investigator
Stephen O’Brien
Sites
n=172. Thanks to all our investigators and site staff.
Patients
n=814. A huge thank you to all participating patients.
NCRI CML Working Group
Dragana Milojkovic, Jenny Byrne, Hugues de Lavallade, Adam Mead, Graeme
Smith, Brian Huntley, Richard Szydlo, Andy Goringe, Naumann Butt, Sameer
Tulpule, Shamyla Siddique, Bernie Ramsahoye, Mhairi Copland (Chair)
814 patients recruited
Recruitment closed Feb 2013
172 hospitals set up
145 recruited patients
SPIRIT 2: study design
Arm A
Imatinib 400
Chronic phase CML
N=407
within 3 months of
diagnosis
R
n=814
Arm B
Dasatinib 100
N=407
Randomised, open label
Primary endpoint: 5 year EFS
Secondary: cytogenetic, PCR response, toxicity
SPIRIT 2 summary
• Largest investigator-conducted randomised trial of
dasatinib vs imatinib
• n=814
• median follow up 3 years
• Both drugs generally well tolerated
• 523 of 812 (64.4%) continue on study medication
• Imatinib: GI tox; Dasatinib: pleural effusions, headaches
• No difference in cardiovascular events
• MR3 rate at one year is: imatinib 43%, dasatinib 58%
• 783/812 (96.4%) remain alive overall
• No difference in progression or overall survival
Overall Survival (OS)
BCR-ABL (IS) at 3 months ≤1% vs. 1-10% vs. >10%
≤1%
1-10%
>10%
BCR-ABL (IS)
≤1%
1-10%
>10%
Hanfstein et al.
Leukemia. 2012 Mar 26. doi: 10.1038/leu.2012.85
n
5Y-OS
218 97%
p-value
n.s.
283 94%
191 87%
0.012
risk
benefit
Stage
1
Stage
2
Stage 3
Randomise
Selective switch
(500 to each
group)
(3 months or later)
Reduce dose, stop
(after minimum 3 years)
Imatinib
Imatinib
Group
I
Ponatinib
Ponatinib
Ponatinib
Ponatinib
R
Nilotinib
n=500
Nilotinib
Nilotinib
Primary endpoint
MR3 at 3 years
(if MR3 for at least 1 year)
n=500
Aim to reduce and stop
Imatinib
Group
N
www.spirit-cml.org
CML
Research for better treatment
Steve O’Brien
Northern Institute for Cancer Research
Newcastle University Medical School
CML patient meeting, 11th October 2014
csg.ncri.org.uk/groups-list/