Leukaemia Lymphoma Research and NCRI Working Group Pick a Winner Programme (LI-1) Trial

ISRCTN	ISRCTN40571019
DOI	https://doi.org/10.1186/ISRCTN40571019
EudraCT/CTIS number	2011-000749-19
Secondary identifying numbers	Version 1, November 2010

Submission date: 29/11/2010
Registration date: 14/03/2011
Last edited: 04/10/2021

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://cancerhelp.cancerresearchuk.org/trials/a-trial-looking-sapacitabine-AC220-vosaroxin-cytarabine-acute-myeloid-leukaemia-aml-li-1

Study website

Contact information

Prof Alan Burnett
Scientific

Department of Haematology
7th floor, School of Medicine
University Hospital of Wales
Heath Park
Cardiff
CF14 4XN
United Kingdom

Study information

Study design	Multicentre phase II/III interventional study
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 contact details below to request a patient information sheet
Scientific title	Leukaemia Lymphoma Research and NCRI Working Group Pick a Winner Programme (LI-1) Trial Trial: Multicentre phase II/III interventional study
Study acronym	LI-1
Study objectives	Standard care treatment for Acute Myeloid Leukaemia (AML) patients over the age of 60 not fit for intensive chemotherapy may be improved upon either in combination with novel agents or by use of novel agents alone
Ethics approval(s)	LI-1 is being submitted to MREC for Wales in December 2010 or January 2011
Health condition(s) or problem(s) studied	Acute myeloid leukemia (AML) patients over 60
Intervention	The following treatments will be compared 1. Low dose Ara-C (cytarabine): 20 mg twice a day (b.i.d) by subcutaneous injection daily on days 1-10 (20 doses) to be repeated at 28 to 42 day intervals. 2. Sapacitabine: 300mg orally b.i.d. for 3 consecutive days in week one and in week two. This should be followed by a minimum of 4 weeks of no treatment. This comprises one course. 3. Vosaroxin: Intravenous infusion in a dose of 72mg/m2 over 10 minutes on days 1 and 4 of each treatment course (two doses). 4. Low dose Ara-C + Vosaroxin: as above 5. Low dose Ara-C + AC220: Ara-C as above plus AC220 oral solution at allocated dose (135mg or 90mg or 60mg) once a day on an empty stomach at least 1 hour before or 2 hours after a meal in the morning for 21 consecutive days as 1 cycle of treatment. 6. 'Other novel agent' Recruitment will proceed until at least 50 patients have entered each comparative arm (Ara-C and novel therapy). For treatments where the proposed effect is to improve survival by inducing a greater number of remissions, this component will then be analysed using complete remission as the measure. Patients will be expected to receive four courses of treatment and are followed up annually for life.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II/III
Drug / device / biological / vaccine name(s)	Ara-C (cytarabine), sapacitabine, vosaroxin, quizartinib (AC220), tosedostat (CHR-2797)
Primary outcome measure	1. Overall survival 2. Complete remission (CR + CRi) achievement and reasons for failure (for induction questions) assessed locally via bone marrow samples (as per standard care) after each course 3. Duration of response (CR, CRi) relapse rates and deaths in first CR 4. Toxicity, both haematological and non-haematological 5. Supportive care requirements (and other aspects of health economics) 6. Quality of Life Assessment
Secondary outcome measures	1. Presence of a cytogenetic abnormality in the bone marrow of patients in morphological remission 2. Molecular characteristics and response to treatment
Overall study start date	01/04/2011
Completion date	01/01/2020

Eligibility

Participant type(s)	Patient
Age group	Senior
Sex	Both
Target number of participants	1000
Total final enrolment	243
Key inclusion criteria	1. Patients have one of the forms of acute myeloid leukaemia, except Acute Promyelocytic Leukaemia as defined by the WHO Classification (Appendix A) this can be any type of de novo or secondary AML or high risk Myelodysplastic Syndrome, defined as greater than 10% marrow blasts (RAEB-2) 2. Normally over the age of 60, but patients under this age are eligible if they are not considered fit for the NCRI AML16 trial or any subsequent equivalent trial 3. Written informed consent 4. For the AC220 interventions cardiac criteria must be met. Electrolyte levels of potassium, magnesium and calcium must be within the institutional normal range
Key exclusion criteria	1. Patients have previously received cytotoxic chemotherapy for AML. (Hydroxycarbamide or similar low-dose therapy, to control the white count is not an exclusion criterion) 2. For AC220 treatment the following criteria make a patient ineligible for that randomisation: 2.1. A myocardial infarction within 12 months 2.2. Uncontrolled angina within 6 months 2.3. Current or history of congestive heart failure New York Heart Association (NYHA) class 3 or 4, unless an echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) performed either within 1 month prior to study screening or during screening results in a left ventricular ejection fraction (LVEF) that is ≥ 45% (or institutional lower limit of normal value) 2.4. Diagnosed or suspected congenital long QT syndrome. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, torsades de pointes [TdP]) or any history of arrhythmia will be discussed with the clinical coordinator/safety physician prior to patients entry into the study 2.5. Prolonged QTcF interval on pre-entry ECG (≥450 ms) 2.6. Any history of second or third degree heart block (may be eligible if the patient currently has a pacemaker 2.7. Heart rate < 50/minute on pre-entry ECG 2.8. Uncontrolled hypertension 2.9. Obligate need for a cardiac pacemaker 2.10. Complete left bundle branch block 2.11. Atrial fibrillation 3. In blast transformation of chronic myeloid leukaemia (CML) 4. Concurrent active malignancy under treatment 5. Pregnant or lactating 6. Acute Promyelocytic Leukaemia 7. Known infection with human immunodeficiency virus (HIV)
Date of first enrolment	01/04/2011
Date of final enrolment	01/01/2019

Locations

Countries of recruitment

Australia
Denmark
France
United Kingdom
Wales

Study participating centre

Department of Haematology,

Cardiff
CF14 4XN
United Kingdom

Sponsor information

Cardiff University (UK)
University/education

6th floor
Research And Commercial Division
30-36 Newport Road
Cardiff
CF24 0DE
Wales
United Kingdom

"ROR"	https://ror.org/03kk7td41

Funders

Funder type

Other

Leukaemia and Lymphoma Research (LLR) (UK)
Private sector organisation / Other non-profit organizations

Location: United Kingdom

Cardiff University (UK)
Private sector organisation / Universities (academic only)

Location: United Kingdom

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?
Results article	Results for combination of low-dose ara-C plus tosedostat versus low-dose ara-C alone	01/07/2021	10/05/2021	Yes	No
Results article	Results for combination of low-dose ara-C plus quizartinib versus low-dose ara-C alone	01/10/2021	04/10/2021	Yes	No

Editorial Notes

04/10/2021: The following changes have been made:
1. Publication reference added.
2. Tosedostat and quizartinib have been added to the drug names.
3. The EudraCT number has been added.
10/05/2021: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
04/04/2017: The overall trial end date was changed from 01/04/2016 to 01/01/2020.