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 |
| EudraCT/CTIS number | 2005-002846-14 |
| ClinicalTrials.gov number | NCT00454480 |
| Secondary identifying numbers | NA |
- 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
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
Scientific
Department of Haematology
University of Wales College of Medicine
Heath Park
Cardiff
CF14 4XN
United Kingdom
| Phone | +44 (0)29 2074 2375 |
|---|---|
| BurnettAK@Cardiff.ac.uk |
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Participant 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 |
| 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 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(s) | MREC for Wales on 16/12/2005 (ref: 05/MRE09/84) |
| 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | DA and DClo, Mylotarg, Azacytidine, Ara-C, Zarnestra, Clofarabine |
| Primary outcome measure | 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. |
| 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 study start date | 01/10/2005 |
| Overall study end date | 03/04/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Senior |
| Sex | Both |
| Target number of participants | 2500 (or until all relevant questions have been answered) |
| Total final enrolment | 2247 |
| 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 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
- Wales
Study participating centre
Department of Haematology
Cardiff
CF14 4XN
United Kingdom
CF14 4XN
United Kingdom
Sponsor information
Cardiff University (UK)
University/education
University/education
Department of Haematology
University of Wales College of Medicine
Heath Park
Cardiff
CF14 4XN
Wales
United Kingdom
| Phone | +44 (0)29 2074 2375 |
|---|---|
| BurnettAK@Cardiff.ac.uk | |
"ROR" |
https://ror.org/03kk7td41 |
Funders
Funder type
Not defined
Clinical Trials Advisory and Awards Committee (CTAAC). Ref. No. C4999/A6031.
No information available
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 | 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 | |
| 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 |
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.
