Condition category
Cancer
Date applied
17/08/2005
Date assigned
11/10/2005
Last edited
11/11/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Prof Alan Burnett

ORCID ID

Contact details

Department of Haematology
University of Wales College of Medicine
Heath Park
Cardiff
CF14 4XN
United Kingdom
+44 (0)29 2074 2375
BurnettAK@Cardiff.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT00454480

Protocol/serial number

NA

Study information

Scientific title

Acronym

AML16

Study hypothesis

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

MREC for Wales on 16/12/2005 (ref: 05/MRE09/84)

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Patient information can be found at: http://www.aml16.bham.ac.uk/Trial/2st%20Amendment%20May%202006/AML16%20PIS%201%20version%204%20May%202006%20tracked%20changes%20accepted.doc

Condition

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 names

DA and DClo, Mylotarg, Azacytidine, Ara-C, Zarnestra, Clofarabine

Primary outcome measures

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 non–intensive treatments:

Overall survival, including survival at 6 months for the initial assessment of whether to continue with a novel therapy.

Secondary outcome measures

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.

Overall trial start date

01/10/2005

Overall trial end date

01/01/2012

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Senior

Gender

Both

Target number of participants

2500 (or until all relevant questions have been answered)

Participant 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

Recruitment start date

01/10/2005

Recruitment end date

01/01/2012

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Department of Haematology
Cardiff
CF14 4XN
United Kingdom

Sponsor information

Organisation

Cardiff University (UK)

Sponsor details

Department of Haematology
University of Wales College of Medicine
Heath Park
Cardiff
CF14 4XN
United Kingdom
+44 (0)29 2074 2375
BurnettAK@Cardiff.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Not defined

Funder name

Clinical Trials Advisory and Awards Committee (CTAAC). Ref. No. C4999/A6031.

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

Results - basic reporting

Publication summary

2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23838349
2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/24062403

Publication citations

  1. Results

    Burnett AK, Russell NH, Hunter AE, Milligan D, Knapper S, Wheatley K, Yin J, McMullin MF, Ali S, Bowen D, Hills RK, , Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival., Blood, 2013, 122, 8, 1384-1394, doi: 10.1182/blood-2013-04-496596.

  2. Results

    Freeman SD, Virgo P, Couzens S, Grimwade D, Russell N, Hills RK, Burnett AK, Prognostic relevance of treatment response measured by flow cytometric residual disease detection in older patients with acute myeloid leukemia., J. Clin. Oncol., 2013, 31, 32, 4123-4131, doi: 10.1200/JCO.2013.49.1753.

Additional files

Editorial Notes