FLAMSA-BU conditioning regimen in patients with acute myeloid leukaemia and myelodysplasia undergoing allogeneic stem cell transplantation

ISRCTN ISRCTN50855000
DOI https://doi.org/10.1186/ISRCTN50855000
EudraCT/CTIS number 2012-005538-12
Secondary identifying numbers 14772
Submission date
11/10/2013
Registration date
11/10/2013
Last edited
12/05/2022
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.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-different-combinations-of-drugs-before-a-stem-cell-transplant-for-aml-or-mds-figaro

Contact information

Dr Sarah Essex
Scientific

School of Cancer Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom

Email figaro@trials.bham.ac.uk

Study information

Study designRandomised interventional treatment trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details to request a patient information sheet
Scientific titleA randomised trial of the FLAMSA-BU conditioning regimen in patients with acute myeloid leukaemia and myelodysplasia undergoing allogeneic stem cell transplantation
Study acronymFIGARO
Study objectivesThis is a prospective, phase II, multicentre, randomised clinical trial in patients with acute myeloid leukaemia (AML) or myelodysplasia (MDS) undergoing reduced intensity conditioning (RIC) allogeneic stem cell transplantation (SCT) comparing the novel conditioning regimen (fludarabine/cytarabine/amsacrine/busulphan/ATG) (FLAMSA-BU) with standard conditioning regimens fludarabine/melphalan/alemtuzumab (FMA), fludarabine/busulphan/alemtuzumab (FBA) or fludarabine/busulphan/ATG (FB-ATG).
Ethics approval(s)NRES Committee Yorkshire & The Humber – Sheffield, 03/06/2013, ref: 13/YH/0152
Health condition(s) or problem(s) studiedTopic: National Cancer Research Network; Subtopic: Haematological Oncology; Disease: Leukaemia (acute myeloid)
InterventionPatients will be stratified at randomisation by their underlying disease (AML; MDS), cytogenetic risk group (adverse risk; intermediate or good risk), disease status at transplant [1st complete remission (CR1) or 2nd complete remission (CR2)]; primary refractory disease, intended control arm regimen (FMA; FBA; FB-ATG), age (above; below 60 years of age) and by donor type (sibling; unrelated).

Patients eligible for entry into the trial will be randomised on a 1:1 basis

Standard conditioning regimens fludarabine/melphalan/alemtuzumab (FMA), fludarabine/busulphan/alemtuzumab (FBA) or fludarabine/busulphan/ATG (FB-ATG).

Novel conditioning regimen, Using fludarabine, cytarabine, amsacrine, busulphan and ATG combined to condition the patients for a reduced intensity stem cell transplant.

The interventions are from 7 to 12 days depending in which treatment arm is selected. The follow-up is 24 months for both arms.

Study Entry : Single Randomisation only
Intervention typeDrug
Pharmaceutical study type(s)
PhasePhase II
Drug / device / biological / vaccine name(s)Fludarabine, cytarabine, amsacrine, busulphan
Primary outcome measureOverall survival, measured using date of death from any cause; Timepoints: 24 months post transplant
Secondary outcome measures1. Disease relapse, measured using date of relapse; Timepoint(s): Disease relapse within the 24 month follow up
2. Event free survival, measured using date of relapse or date of death; Timepoint(s): 24 months post transplant
3. Incidence of graft versus host disease (GvHD), measured counting episodes of GvHD; Timepoint(s): Throughout the 24 month follow up
4. Quality of Life; Timepoint(s): FACT-BMT questionnaire, completed pre-tranplant, at day 42 and month 3, 6, 9, 12, 18 and 24.
5. Transplant related mortality measured by any death related to transplant procedure, not underlying, disease at day 100 and 12 months post-transplant
Overall study start date10/10/2013
Completion date31/10/2015

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participantsUK Sample Size: 170
Total final enrolment244
Key inclusion criteria1. Patients with a morphologically documented diagnosis of AML or MDS clinically indicated to receive a RIC allograft with one the following disease characteristics:
AML
1.1. Patients in 1st complete remission (CR1) with adverse risk cytogenetics
1.2. Patients in 2nd complete remission (CR2)
1.3. Patients with primary refractory AML defined as the failure to achieve a morphological remission after 2 courses of induction chemotherapy
1.4. Patients participating in the UK NCRN AML17 (or the subsequent AML19) clinical trial who have been defined as high risk (based upon age, de novo or secondary disease, cytogenetics, white blood count, sex and response to course 1)
1.5. Patients participating in the UK NCRN AML17, AML18 (or the subsequent AML19) clinical trials who have been defined as high risk by Minimal Residual Disease (MRD) criteria
MDS
1.6. Patients with advanced MDS (defined by an IPSS score of INT1 with >5% blasts or INT2 or high risk ) who have < 5% blasts at the time of randomisation following chemotherapy or hypomethylating agents if necessary
2. Patients aged ≥ 16 years
3. Patients with an HLA identical sibling or suitable matched unrelated donor (suitable match defined as no greater
than a single allele mismatch at HLA A, B, C or DRB1)
4. Patients considered suitable to undergo a reduced intensity conditioned allogeneic stem cell transplant as clinically judged by the Local Investigator including:
4.1. Adequate cardiac, pulmonary, hepatic and renal function as determined by pre-transplant assessments
4.2. Resolution of any toxic effects of prior therapy (including radiotherapy, chemotherapy or surgical procedures)
5. Patients with an ECOG performance status of 0, 1 or 2
6. Patients have given written informed consent
7. Patients willing and able to comply with scheduled study visits and laboratory tests
Key exclusion criteria1. Patients with chemorefractory relapse of AML or MDS
2. Patients with contraindications to receiving RIC allogeneic SCT
3. Female patients who are pregnant or breastfeeding. All women of childbearing potential must have a negative pregnancy test before commencing treatment
4. Adults of reproductive potential not willing to use appropriate, effective, contraception during the specified period
5. Patients with clinically significant cardiac disease (New York Heart Association, Class III or IV)
6. Patients with renal or hepatic impairment as clinically judged by Local Investigator
7. Patients with active infection, HIV positive or chronic active Hep A, B, C
8. Patients with concurrent active malignancy
Date of first enrolment10/10/2013
Date of final enrolment31/10/2015

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

University of Birmingham
Birmingham
B15 2TT
United Kingdom

Sponsor information

University of Birmingham (UK)
University/education

Edgbaston
Birmingham
B15 2TT
England
United Kingdom

Email Figaro@trials.bham.ac.uk
Website http://www.birmingham.ac.uk/
ROR logo "ROR" https://ror.org/03angcq70

Funders

Funder type

Charity

Leukaemia and Lymphoma Research; Grant Codes: 12071
Private sector organisation / Other non-profit organizations
Location
United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing planNot provided at time of registration

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Abstract results Presented at ASH 13/11/2019 12/05/2022 No No
Basic results 23/01/2022 12/05/2022 No No
Plain English results 10/05/2022 12/05/2022 No Yes
Results article 01/03/2021 12/05/2022 Yes No
HRA research summary 28/06/2023 No No

Editorial Notes

12/05/2022: The following changes have been made:
1. A plain English results link has been added.
2. Publication references added.
3. The final enrolment number has been added from the reference.
4. A basic results link has been added.
09/11/2017: No publications found, verifying study status with principal investigator.