A trial of directed therapy in younger patients with acute myeloid leukaemia: MRC AML 15

Plain English Summary

http://cancerhelp.cancerresearchuk.org/trials/a-trial-comparing-different-chemotherapy-regimes-and-the-use-of-mylotarg-monoclonal-antibody-in-treatment-of-acute-myeloid-leukaemia

Study website

http://www.aml15.bham.ac.uk/

Type

Scientific

Contact name

Prof AK 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

EudraCT/CTIS number

2005-001149-40

IRAS number

ClinicalTrials.gov number

Protocol/serial number

G9901427

Scientific title

A trial of directed therapy in younger patients with acute myeloid leukaemia: MRC AML 15

Acronym

MRC AML 15

Study hypothesis

The AML trial has two separate parts:
1. For patients with Acute Myeloid Leukaemia (AML), other than acute promyelocytic leukaemia (APL), as defined by the World Health Organisation (WHO) classification (2001).
2. For patients with Acute Promyelocytic Leukaemia (APL).
The objectives for each of these components are summarised below.

Therapeutic questions for patients with non-APL AML: For patients with acute myeloid leukaemia (AML) the aims of the AML15 trial are:
1. To compare two induction schedules (namely DAT and FLAG-Ida)
2. To assess the value of Mylotarg during induction
3. To compare the standard MRC consolidation chemotherapy (i.e. MACE + MidAC) versus high-dose Ara-C
4. For those allocated to high-dose Ara-C to compare high-dose ARA-C during consolidation (see above) at two different doses (1.5 g/m squared versus 3.0g/m squared)
5. To assess the value of Mylotarg during consolidation
6. To compare four versus five courses of treatment in total (where the final course is intermediate-dose Ara-C)
7. In standard and poor risk patients, to evaluate, by means of a genetic randomisation, the value of allogeneic stem cell transplantation [SCT, whether standard allogeneic (allo-SCT) or non-myeloablative ‘mini’ allogeneic (mini-SCT)]

Therapeutic questions for patients with APL. For patients with APL:
1. To compare the MRC approach (i.e. four courses of intensive chemotherapy) with the Spanish approach (based on anthracyclines with maintenance therapy)
2. To assess the value of Mylotarg during consolidation (i.e. with course 3)

Ethics approval(s)

Not provided at time of registration

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Study setting(s)

Not specified

Study type

Not Specified

Patient information sheet

Condition

Leukaemia

Intervention

1. (R1) Patients with acute promyelocytic leukemia (APL) will be randomised to receive oral retinoic acid together with either MRC H-DAT chemotherapy or the Spanish Intermittent Idarubicin. Following confirmation of remission, patients will continue with the MRC (DAT:MACE:MIDAC) or Spanish chemotherapy but will be randomised to receive CMA-676/Myelotarg (Immunoconjugate) on day 1 of course 3 or not. (Patients will be monitered molecularly by Reverse Transcription (RT) and real time Polymerase Chain Reaction (PCR) to predict relapse. Three quality of life assessments will be made at 3, 6 and 9 months and resource use information will be collected for cost benefit analysis.)
2. (R2) Non-APL patients will be randomised to receive induction cources 1 and 2 with H-Dat (Daunorbicin:Ara-C, Thioguanine) or FLA_G IDA (Fludarabine, Ara C, G-CSF, Idarubicin) and to receive CMA-676 (Myelotarg) on day 1 of course 1 or not.
3. Following the first course of chemotherapy the risk profile of each patient will be determined (based on cytogenetics, blast clearance after course 1). Good risk patients (15%) will leave AML15 and will enter the MRC AML High Risk Trial.
4. (R3)(R4) Patients who have completed course 2 and are allocated to the chemotherapy comparisons will be randomised to receive CMA-676 (Myelotarg) on day 1 of course 3.
5. (R5) All patients allocated to allogenic transplant up to 35 years will receive standard conditioning (Cyclophosphamide/TBI) with stem cells obtained from peripheral blood or bone marrow as course 3. For patients 36-50 investigators may choose a conventional transplant or a non-ablative transplant. Patients over 50 years will receive a non-ablative transplant. The non-ablative transplant will be given as course 4, ie patients will receive MACE as course 3 before proceeding to transplant.
7. Patients who relapse at any point in the trial will be entered into the MRC AML HR Trial.

Intervention type

Other

Primary outcome measure

The main endpoints for each comparison will be:
1. Complete remission (CR) achievement and reasons for failure (for induction questions)
2. Duration of remission, relapse rates and deaths in first CR
3. Overall survival
4. Toxicity, both haematological and non-haematological, and quality of life
5. Supportive care requirements (and other aspects of health economics)

Secondary outcome measures

Not provided at time of registration

Overall study start date

01/03/2002

Overall study end date

01/06/2008

Reason abandoned (if study stopped)

Participant inclusion criteria

1. Any form of de novo or secondary AML
2. Suitable for intensive chemotherapy
3. Under 60 years
4. Written consent

Participant type(s)

Patient

Age group

Not Specified

Sex

Not Specified

Target number of participants

3000

Participant exclusion criteria

1. Previous chemotherapy for AML
2. Blast transferration of CML
3. Pregnant or lactating
4. Abnormal liver function tests for Mylotarg randomisations

Recruitment start date

01/03/2002

Recruitment end date

01/06/2008

Countries of recruitment

United Kingdom, Wales

Study participating centre

Department of Haematology
Cardiff
CF14 4XN
United Kingdom

Organisation

Cardiff University (UK)

Sponsor details

-
Cardiff
CF10 3XQ
Wales
United Kingdom
+44 (0)29 2087 4000
abc@email.com

Sponsor type

University/education

Website

ROR

https://ror.org/03kk7td41

Funder type

Research council

Funder name

Medical Research Council (MRC) (UK)

Alternative name(s)

UK Medical Research Council, MRC

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Individual participant data (IPD) sharing plan

Not provided at time of registration

IPD sharing plan summary

Not provided at time of registration

Study outputs