CML Research for better treatment

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CMLResearch for better treatment

• Steve OBrien
• Northern Institute for Cancer Research
• Newcastle University Medical School

CML patient meeting, 11th October 2014
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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

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csg.ncri.org.uk/groups-list/
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CML trials in the UK

• Destiny
• low level disease (MMR)
• reduce then stop if possible
• pilot study
• CHOICES
• SPIRIT trials

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Around the world

• Germany nilotinib
• France interferon alpha
• US dasatinib, early response
• India efficacy of generics

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Thank you
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Acknowledgements
Data analysis and presentation Stephen OBrien, 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 SOB, 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 OBrien
Sites n172. Thanks to all our investigators and site staff.
Patients n814. 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)
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• 814 patients recruited
• Recruitment closed Feb 2013
• 172 hospitals set up
• 145 recruited patients

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SPIRIT 2 study design
Arm A Imatinib 400
Chronic phase CML within 3 months of
diagnosis
N407
n814
Arm B Dasatinib 100
N407
Randomised, open label Primary endpoint 5 year
EFS Secondary cytogenetic, PCR response,
toxicity
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SPIRIT 2 summary

• Largest investigator-conducted randomised trial
  of dasatinib vs imatinib
• n814
• 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

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Overall Survival (OS)BCR-ABL (IS) at 3 months
1 vs. 1-10 vs. gt10
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1-10
gt10
BCR-ABL (IS) n 5Y-OS 1
218 97 1-10 283 94 gt10 191 87
p-value
n.s.
0.012
Hanfstein et al. Leukemia. 2012 Mar 26. doi
10.1038/leu.2012.85
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risk
benefit
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Stage 1 Randomise (500 to each group)
Stage 2 Selective switch (3 months or later)
Stage 3 Reduce dose, stop (after minimum 3 years)
Imatinib
Imatinib
Group I
Imatinib
n500
Ponatinib
Ponatinib
R
Aim to reduce and stop (if MR3 for at least 1
year)
Ponatinib
Ponatinib
Group N
Nilotinib
n500
Nilotinib
Nilotinib
Primary endpoint MR3 at 3 years
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www.spirit-cml.org
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CMLResearch for better treatment

• Steve OBrien
• Northern Institute for Cancer Research
• Newcastle University Medical School

CML patient meeting, 11th October 2014
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csg.ncri.org.uk/groups-list/