CMLResearch for better

treatment

Steve O’BrienNorthern Institute for Cancer Research

Newcastle University Medical School

CML patient meeting, 11th October 2014

Clinical trialsPhase I studies designed to find out the most effective dose

of thedrug and the possible side effects of the drug.

Phase II studies carried out on different cancers so that theresearch team can find out how active a particular drug is. Onlyabout 20 to 30 patients with each cancer.

Phase III studies to compare a new treatment with the besttreatment currently available.Phase III trials are usually randomised and may include a doubleblind procedure.

Others include – Sample banking; Epidemiological and phase IVlong term safety monitoring usually post approval

csg.ncri.org.uk/groups-list/

CML trials in the UKDestinylow level disease (MMR)reduce then stop if possiblepilot study

CHOICES

SPIRIT trials

Around the worldGermany – nilotinib

France – interferon alpha

US – dasatinib, early response

India – efficacy of generics

Thank you…

AcknowledgementsData 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 up145 recruited patients

SPIRIT 2: study design

Chronic phase CML

within 3 months of diagnosis

Arm AImatinib 400

Arm BDasatinib 100

Randomised, open labelPrimary endpoint: 5 year EFSSecondary: cytogenetic, PCR response, toxicity

n=814

N=407

N=407

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

⅔

BCR-ABL (IS) n 5Y-OS

≤1% 218 97%

1-10% 283 94%

>10% 191 87%

Overall Survival (OS)

BCR-ABL (IS) at 3 months ≤1% vs. 1-10% vs. >10%

n.s.

0.012

p-value

≤1%1-10%

>10%

Hanfstein et al.Leukemia. 2012 Mar 26. doi: 10.1038/leu.2012.85

risk benefit

RR

Imatinib Imatinib

NilotinibNilotinib

GroupI

GroupN

Imatinib Imatinib

PonatinibPonatinib

PonatinibPonatinib

NilotinibNilotinib

Stage 1

Randomise(500 to each

group)

Stage 2

Selective switch

(3 months or later)

Stage 3

Reduce dose, stop

(after minimum 3 years)

Primary endpoint

MR3 at 3 years

Imatinib Imatinib

PonatinibPonatinib

PonatinibPonatinib

NilotinibNilotinib

Aim

to re

duce

and

sto

p(if

MR3

for a

t lea

st 1

yea

r)Ai

m to

redu

ce a

nd s

top

(if M

R3 fo

r at l

east

1 y

ear)

n=500

n=500

www.spirit-cml.org

CMLResearch for better

treatment

Steve O’BrienNorthern Institute for Cancer Research

Newcastle University Medical School

CML patient meeting, 11th October 2014

csg.ncri.org.uk/groups-list/