STI571 Prospective International RandomIsed Trial 2: A phase III, prospective randomised comparison of imatinib (STI571, Glivec®/ Gleevec®) 400 mg daily versus dasatinib (Sprycel®) 100 mg daily in patients with newly-diagnosed chronic phase chronic myeloid leukaemia

ISRCTN	ISRCTN54923521
DOI	https://doi.org/10.1186/ISRCTN54923521
EudraCT/CTIS number	2007-006185-15
ClinicalTrials.gov number	NCT01460693
Secondary identifying numbers	4443

Submission date: 17/04/2008
Registration date: 09/10/2008
Last edited: 20/03/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-imatinib-and-dasatinib-for-newly-diagnosed-chronic-myeloid-leukaemia

Study website

Contact information

Ms Corinne Hedgley
Scientific

Newcastle University
Academic Haematology
School of Clinical & Laboratory Sciences
Leech Building, Medical School
Framlington Place
Newcastle upon Tyne
NE2 4HH
United Kingdom

Phone	+44 (0)1280 814 916
Email	c.a.hedgley@ncl.ac.uk

Study information

Study design	Phase III, multicentre, open-label, prospective randomised controlled 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	STI571 Prospective International RandomIsed Trial 2: A phase III, prospective randomised comparison of imatinib (STI571, Glivec®/ Gleevec®) 400 mg daily versus dasatinib (Sprycel®) 100 mg daily in patients with newly-diagnosed chronic phase chronic myeloid leukaemia
Study acronym	SPIRIT 2
Study objectives	To compare 5-year Event Free Survival (EFS) between the treatment arms. The study is powered to demonstrate superiority of the dasatinib arm over the imatinib arm.
Ethics approval(s)	London Research Ethics Committee in 11/2007 (ref: 07/H0718/90)
Health condition(s) or problem(s) studied	Newly diagnosed, chronic-phase, chronic myeloid leukaemia
Intervention	Arm 1: Imatinib (oral) 400 mg daily, to be taken for a minimum of 5 years Arm 2: Dasatinib (oral) 100 mg daily, to be taken for a minimum of 5 years All endpoints will be assessed at regular timepoints throughout the trial for a minimum of 5 years per patient. Contact details of Principal Investigator: Dr Stephen O'Brien Newcastle University Academic Haematology School of Clinical & Laboratory Sciences Leech Building, Medical School Framlington Place Newcastle upon Tyne NE2 4HH United Kingdom
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase III
Drug / device / biological / vaccine name(s)	STI571 (Glivec®/ Gleevec®) and dasatinib (Sprycel®).
Primary outcome measure	Event -free survival at 5 years
Secondary outcome measures	1. To compare the rate of complete cytogenetic response after 2 years 2. To compare the treatment failure rates (TFR) at 5 years 3. To compare the rates of complete haematologic response (CHR). Duration of follow-up: 60 months 4. To compare the level of 'molecular' response (BCR-ABL/ABL ratio by real time polymerase chain reaction [PCR]). Duration of follow-up: 60 months 5. To compare the tolerability between the regimens. This will in part be incorporated into the treatment failure assessment. Duration of follow-up: 60 months 6. To assess quality of life by the EQ-5D and the Functional Assessment of Cancer Treatment-Biological Response Modifier (FACT-BRM) questionnaires. Timepoints of assessment: at screening and then Months 1, 2, 3, 6, 12, 24, 36, 48, 60 7. To assess the broad comparative costs between the regimens 8. To compare overall survival at 2 and 5 years
Overall study start date	30/06/2008
Completion date	30/06/2016

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	810
Key inclusion criteria	1. Male or female patients >= 18 years of age 2. Patients must have all of the following: 2.1. Be enrolled within 3 months of initial diagnosis of chronic myeloid leukaemia - chronic phase (CML-CP) (date of initial diagnosis is the date of first cytogenetic analysis) 2.2. Cytogenetic confirmation of the Philadelphia chromosome or variants of (9;22) translocations; patients may have secondary chromosomal abnormalities in addition to the Philadelphia chromosome 2.3. <15% blasts in peripheral blood and bone marrow 2.4. <30% blasts plus promyelocytes in peripheral blood and bone marrow 2.5. <20% basophils in peripheral blood 2.6. >= 100 x 10^9/L platelets 2.7. No evidence of extramedullary leukaemic involvement, with the exception of hepatosplenomegaly 3. Written voluntary informed consent
Key exclusion criteria	1. Patients with Ph-negative, BCR-ABL-positive disease are not eligible for the study 2. Any prior treatment for CML with: any tyrosine kinase inhibitor (e.g., imatinib, dasatinib, nilotinib); busulphan; interferon-alpha; homoharringtonine; cytosine arabinoside; any other investigational agents (hydroxycarbamide and anagrelide are the only drugs permitted). NB: Patients will be ineligible for the study if they have received any prior therapy with interferon-alpha or imatinib. No exceptions. 3. Patients who received prior chemotherapy, including regimens used in peripheral blood progenitor cells (PBPCs) mobilisation for haematopoietic progenitor-cell transplantation (It is allowable to collect unmobilised PBPCs at diagnosis) 4. Patient who have had any form of prior haemopoietic stem cell transplant, either autograft or allograft 5. Patients with an Eastern Cooperative Oncology Group (ECOG) Performance Status Score >= 3 6. Patients with serum bilirubin, aspartate aminotransferase (SGOT/AST), alanine aminotransferase (SGPT/ALT), or creatinine concentrations > 2.0 x the institutional upper limit of the normal range (IULN) 7. Patients with International normalised ratio (INR) or partial thromboplastin time (PTT) >1.5 x IULN, with the exception of patients on treatment with oral anticoagulants 8. Patients with uncontrolled medical disease such as diabetes mellitus, thyroid dysfunction, neuropsychiatric disorders, infection, angina, or Grade 3/4 cardiac problems as defined by the New York Heart Association Criteria 9. Patients with known positivity for human immunodeficiency virus (HIV); baseline testing for HIV is not required 10. Patients who have undergone major surgery within 4 weeks of Study Day 1, or who have not recovered from prior major surgery 11. Patients who are: 11.1 Pregnant 11.2. Breast feeding 11.3. Of childbearing potential without a negative pregnancy test prior to Study Day 1 11.4. Male or female of childbearing potential unwilling to use barrier contraceptive (Amenorrhoeic for at least 12 months to be considered of non-childbearing potential) 12. Patients with a history of another malignancy either currently or within the past five years, with the exception of basal cell skin carcinoma or cervical carcinoma in situ 13. Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable
Date of first enrolment	30/06/2008
Date of final enrolment	30/06/2016

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Newcastle University

Newcastle upon Tyne
NE2 4HH
United Kingdom

Sponsor information

Newcastle-upon-Tyne Hospitals NHS Foundation Trust (UK)
Hospital/treatment centre

R&D Department
4th Floor
Leazes Wing
Royal Victoria Infirmary
Queen Victoria Road
Newcastle upon Tyne
NE1 4LP
England
United Kingdom

Website	http://www.newcastle-hospitals.org.uk
"ROR"	https://ror.org/05p40t847

Funders

Funder type

Industry

Bristol Myers-Squibb (USA)
Government organisation / For-profit companies (industry)

Alternative name(s): Bristol-Myers Squibb Company, BMS
Location: United States of America

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?
Basic results				No	No
Results article	results	12/07/2012	10/04/2019	Yes	No
Results article	results	04/04/2013	10/04/2019	Yes	No

Editorial Notes

20/03/2020: EudraCT number added. Added EudraCT link to basic results (scientific).
10/04/2019: Publication reference added.