TY - JOUR
T1 - Venetoclax combined with low dose cytarabine compared to standard of care intensive chemotherapy for the treatment of favourable risk adult acute myeloid leukaemia (VICTOR)
T2 - Study protocol for an international, open-label, multicentre, molecularly-guided randomised, phase II trial
AU - Dillon, Richard
AU - Maycock, Shanna
AU - Jackson, Aimee
AU - Fox, Sonia
AU - Freeman, Sylvie
AU - Craddock, Charles
AU - Thomas, Catherine
AU - Homer, Emma
AU - Leahy, Jane
AU - Mamwell, Anna
AU - Potter, Nicola
AU - Russell, Nigel
AU - Wei, Andrew
AU - Ommen, Hans Beier
AU - Hemmaway, Claire
AU - Knapper, Steve
AU - Billingham, Lucinda
N1 - © 2022. The Author(s).
PY - 2022/11/14
Y1 - 2022/11/14
N2 - BACKGROUND: For patients with acute myeloid leukaemia (AML), the only potentially curative treatment is intensive chemotherapy (IC). This is highly toxic, particularly for patients > 60 years, potentially leading to prolonged hospitalisations requiring intensive supportive care, and sometimes treatment-related death. This also results in extensive healthcare costs and negatively impacts quality of life (QoL). Venetoclax with low-dose cytarabine (VEN + LDAC) is a novel, low-intensity treatment for AML patients who cannot receive IC. VEN + LDAC is given as an outpatient and toxicity appears significantly lower than with IC. Analysis of clinical trials performed to date are promising for patients with the genotype NPM1mutFLT3 ITDneg, where remission and survival rates appear comparable to those achieved with IC.METHODS: VICTOR is an international, two-arm, open-label, multi-centre, non-inferiority, randomised-controlled phase II trial to assess VEN + LDAC compared to standard of care (IC) as first-line treatment in older patients (initially aged ≥ 60 years) with newly diagnosed AML. The trial will recruit patients with a NPM1mutFLT3 ITDneg genotype; those with a favourable risk in relation to the experimental treatment. University of Birmingham is the UK co-ordinating centre, with national hubs in Aarhus University Hospital, Denmark, and Auckland District Health Board, New Zealand. The primary outcome is molecular event-free survival time where an event is defined as failure to achieve morphological complete response (CR) or CR with incomplete blood count recovery after two cycles of therapy; molecular persistence, progression or relapse requiring treatment change; morphological relapse, or; death. Secondary outcomes include cumulative resource use at 12- and 24-months, and QoL as assessed by EORTCQLQ-C30 and EQ-5D-3L at 3-, 6-, 12-, 18- and 24-months. The trial employs an innovative Bayesian design with target sample size of 156 patients aged > 60 years.DISCUSSION: The principle underpinning the VICTOR trial is that the chance of cure for patients in the experimental arm should not be compromised, therefore, an adaptive design with regular checks on accumulating data has been employed, which will allow for a staged expansion of the trial population to include younger patients if, and when, there is sufficient evidence of non-inferiority in older patients.TRIAL REGISTRATION: EudraCT: 2020-000,273-24; 21-Aug-2020.ISRCTN: 15,567,173; 08-Dec-2020.
AB - BACKGROUND: For patients with acute myeloid leukaemia (AML), the only potentially curative treatment is intensive chemotherapy (IC). This is highly toxic, particularly for patients > 60 years, potentially leading to prolonged hospitalisations requiring intensive supportive care, and sometimes treatment-related death. This also results in extensive healthcare costs and negatively impacts quality of life (QoL). Venetoclax with low-dose cytarabine (VEN + LDAC) is a novel, low-intensity treatment for AML patients who cannot receive IC. VEN + LDAC is given as an outpatient and toxicity appears significantly lower than with IC. Analysis of clinical trials performed to date are promising for patients with the genotype NPM1mutFLT3 ITDneg, where remission and survival rates appear comparable to those achieved with IC.METHODS: VICTOR is an international, two-arm, open-label, multi-centre, non-inferiority, randomised-controlled phase II trial to assess VEN + LDAC compared to standard of care (IC) as first-line treatment in older patients (initially aged ≥ 60 years) with newly diagnosed AML. The trial will recruit patients with a NPM1mutFLT3 ITDneg genotype; those with a favourable risk in relation to the experimental treatment. University of Birmingham is the UK co-ordinating centre, with national hubs in Aarhus University Hospital, Denmark, and Auckland District Health Board, New Zealand. The primary outcome is molecular event-free survival time where an event is defined as failure to achieve morphological complete response (CR) or CR with incomplete blood count recovery after two cycles of therapy; molecular persistence, progression or relapse requiring treatment change; morphological relapse, or; death. Secondary outcomes include cumulative resource use at 12- and 24-months, and QoL as assessed by EORTCQLQ-C30 and EQ-5D-3L at 3-, 6-, 12-, 18- and 24-months. The trial employs an innovative Bayesian design with target sample size of 156 patients aged > 60 years.DISCUSSION: The principle underpinning the VICTOR trial is that the chance of cure for patients in the experimental arm should not be compromised, therefore, an adaptive design with regular checks on accumulating data has been employed, which will allow for a staged expansion of the trial population to include younger patients if, and when, there is sufficient evidence of non-inferiority in older patients.TRIAL REGISTRATION: EudraCT: 2020-000,273-24; 21-Aug-2020.ISRCTN: 15,567,173; 08-Dec-2020.
KW - Humans
KW - Adult
KW - Aged
KW - Cytarabine
KW - Quality of Life
KW - Bayes Theorem
KW - Standard of Care
KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects
KW - Neoplasm Recurrence, Local/drug therapy
KW - Leukemia, Myeloid, Acute/drug therapy
KW - Antineoplastic Agents/therapeutic use
KW - Nuclear Proteins
KW - Clinical Trials, Phase II as Topic
KW - Multicenter Studies as Topic
U2 - 10.1186/s12885-022-10221-2
DO - 10.1186/s12885-022-10221-2
M3 - Article
C2 - 36376888
SN - 1471-2407
VL - 22
JO - BMC Cancer
JF - BMC Cancer
IS - 1
M1 - 1174
ER -