National Cancer Research Institute acute myeloid leukaemia and high risk MDS trial 16. A trial for older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome (MDS).

ISRCTN	ISRCTN11036523
DOI	https://doi.org/10.1186/ISRCTN11036523
ClinicalTrials.gov (NCT)	NCT00454480
Clinical Trials Information System (CTIS)	2005-002846-14
Protocol serial number	NA
Sponsor	Cardiff University (UK)
Funder	Clinical Trials Advisory and Awards Committee (CTAAC). Ref. No. C4999/A6031.

Submission date: 17/08/2005
Registration date: 11/10/2005
Last edited: 25/01/2022

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.cancerhelp.org.uk/trials/a-trial-looking-at-treatment-for-acute-myeloid-leukaemia-and-high-risk-myelodysplastic-syndrome-intensive-treatment-group
http://www.cancerhelp.org.uk/trials/a-trial-looking-at-treatment-for-acute-myeloid-leukaemia-and-high-risk-myelodysplastic-syndrome-non-intensive-treatment-group

Contact information

Prof Alan Burnett
Scientific

Department of Haematology
University of Wales College of Medicine
Heath Park
Cardiff
CF14 4XN
United Kingdom

Phone	+44 (0)29 2074 2375
Email	BurnettAK@Cardiff.ac.uk

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	National Cancer Research Institute acute myeloid leukaemia and high risk MDS trial 16. A trial for older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome (MDS).
Study acronym	AML16
Study objectives	Current study hypothesis as of 04/08/2011: Therapeutic questions for patients considered fit for intensive treatment: 1. To compare two induction schedules (DA and ADE) 2. To assess the value of ATRA during induction when used in combination with DA or ADE for the first 50 days 3. To compare a total of two versus three courses of treatment in patients who achieve at least Partial Remission (<15% blasts) after induction course 1 4. To compare the use of Demethylation maintenance treatment with Azacytidine with no maintenance 5. To assess the value of Reduced Intensity Allogeneic Stem Cell Transplantation as consolidation for patients with matched donors Therapeutic questions for patients not considered fit for intensive treatment: To compare Low Dose Ara-C versus Sapacitabine. Previous options, including clofarabine, have now been completed. As of 15/02/2011 the anticipated end date for this trial has been updated from 01/10/2010 to 31/08/2011. As of 22/07/2011 the end date has again been extended to 01/01/2012. Previous study hypothesis points: 1. To compare two induction schedules (DA and DClo) 2. To assess the value of ATRA during induction when used in combination with DA or DClo in course 1 Therapeutic questions for patients not considered fit for intensive treatment: To compare Low Dose Ara-C versus available novel approaches: Low Dose Ara-C with Mylotarg, Low Dose Ara-C with Zarnestra, Low Dose Clofarabine. During the course of the Programme other novel therapies are expected to become available, and will be considered for inclusion in this comparison.
Ethics approval(s)	MREC for Wales on 16/12/2005 (ref: 05/MRE09/84)
Health condition(s) or problem(s) studied	Acute Myloid Leukaemia (AML) and High Risk Myelodysplastic Syndrome (MDS).
Intervention	Current interventions as of 04/08/2011: Intensive interventions: There are three randomised comparisons within the trial: At diagnosis: i. DA versus ADE ii. ATRA versus not for 60 days As consolidation: i. Three courses versus two courses of total induction/consolidation therapy ii. Non-intensive allogeneic stem cell transplant for patients with donors As maintenance: i. Azacytidine or not for one year Non-Intensive interventions: Low Dose Ara-C versus Low Dose Clofarabine* OR Sapacitabine. *Clofarabine option now closed. For each of these non-intensive options the treatment plan is for four courses to be given. Marrow response should be assessed before each course until complete remission is established. Previous interventions: At diagnosis: i. DA versus DClo ii. Mylotarg versus not in Course 1 for 60 days Non-Intensive interventions: Low Dose Ara-C versus Low Dose Ara-C with Mylotarg OR Low Dose Clofarabine OR Low Dose Ara-C with Zarnestra
Intervention type	Drug
Phase	Phase III
Drug / device / biological / vaccine name(s)	DA and DClo, Mylotarg, Azacytidine, Ara-C, Zarnestra, Clofarabine
Primary outcome measure(s)	For intensive treatment: Overall survival, complete remission (CR) achievement and reasons for failure (for induction questions), duration of remission, relapse rates and deaths in 1st CR. For nonintensive treatments: Overall survival, including survival at 6 months for the initial assessment of whether to continue with a novel therapy.
Key secondary outcome measure(s)	For intensive treatment: Toxicity as assessed by NCI/WHO definitions; days to haematological recovery; supportive care requirements (days on antibiotics, days in hospital, blood product support). For non-intensive treatment: Toxicity as assessed by NCI/WHO definitions; days to haematological recovery; supportive care requirements (days on antibiotics, days in hospital, blood product support); complete remission (CR) achievement and reasons for failure, duration of remission, relapse rates and deaths in 1st CR.
Completion date	03/04/2017

Eligibility

Participant type(s)	Patient
Age group	Senior
Sex	All
Target sample size at registration	2500
Total final enrolment	2247
Key inclusion criteria	1. They have one of the forms of acute myeloid leukaemia, except acute promyelocytic leukaemia, as defined by the World Health Organisation (WHO) Classification - 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. They should normally be over the age of 60, but patients under this age are eligible if they are not considered fit for the MRC AML 15 trial 3. They have given written informed consent
Key exclusion criteria	1. Patients have previously received cytotoxic chemotherapy for AML. (Hydroxyurea, or similar low-dose therapy, to control the white count prior to initiation of intensive therapy is not an exclusion.) 2. They are in blast transformation of chronic myeloid leukaemia (CML) 3. They have a concurrent active malignancy 4. They are pregnant or lactating 5. Patients with abnormal liver function tests exceeding twice the local upper limit of normal are not eligible for the Mylotarg randomisations 6. Patients with Acute Promyelocytic Leukaemia
Date of first enrolment	01/10/2005
Date of final enrolment	01/01/2012

Locations

Countries of recruitment

United Kingdom
Wales

Study participating centre

Department of Haematology

Cardiff
CF14 4XN
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	22/08/2013		Yes	No
Results article	results	10/11/2013		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Plain English results	intensive treatment group results	23/08/2013	25/01/2022	No	Yes
Plain English results	non intensive treatment group results	23/08/2013	25/01/2022	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

25/01/2022: The following changes have been made:
1. The Cancer Research UK lay results summaries have been added.
2. The total final enrolment number has been added.
19/03/2020: EudraCT number added.
23/07/2019: The overall trial end date has been changed from 01/01/2012 to 03/04/2017.