Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
Version 1, November 2010
Study information
Scientific title
Leukaemia Lymphoma Research and NCRI Working Group Pick a Winner Programme (LI-1) Trial Trial: Multicentre phase II/III interventional study
Acronym
LI-1
Study hypothesis
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
LI-1 is being submitted to MREC for Wales in December 2010 or January 2011
Study design
Multicentre phase II/III interventional study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use contact details below to request a patient information sheet
Condition
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
Phase
Phase II/III
Drug names
Ara-C (cytarabine), Sapacitabine, Vosaroxin, AC220
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 trial start date
01/04/2011
Overall trial end date
01/01/2020
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Senior
Gender
Both
Target number of participants
1000
Participant 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)
Recruitment start date
01/04/2011
Recruitment end date
01/01/2019
Locations
Countries of recruitment
Australia, Denmark, France, United Kingdom
Trial participating centre
Department of Haematology,
Cardiff
CF14 4XN
United Kingdom
Funders
Funder type
Other
Funder name
Leukaemia and Lymphoma Research (LLR) (UK)
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Funder name
Cardiff University (UK)
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
Universities (academic only)
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list