Acute myeloid leukaemia Cancer Malignant neoplasms, stated or presumed to be primary, of lymphoid, haematopoietic and related tissue
Conditions
Interventions
VICTOR is a multicentre trial which will open in the UK, Denmark and New Zealand for patients with Acute Myeloid Leukaemia (AML) with NPM1 mutation. It is a randomised controlled trial and patients wi
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Age
55 Years to 120 Years
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 09/02/2024: 1. Diagnosis of CD33-positive acute myeloid leukaemia 2. Age >=55 years (prior to the interim analyses performed after enrolment of 50 and 100 patients) 3. Genotype NPM1mut FLT3 ITDneg (FLT3- Tyrosine Kinase Domain mutation, TKD, is permitted) 4. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2 5. Serum creatinine =60 years (prior to the interim analyses performed after enrolment of 50 and 100 patients) 3. Genotype NPM1mut FLT3 ITDneg (FLT3- Tyrosine Kinase Domain mutation, TKD, is permitted) 4. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2 5. Serum creatinine <=1.5 x ULN (upper limit of normal) 6. Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) <=2.5 ULN and bilirubin <=2 x ULN 7. Able to provide written informed consent 8. Considered fit for intensive chemotherapy with anthracyclines by treating physician
Exclusion criteria
Exclusion criteria: 1. Previous chemotherapy for AML or any antedecent haematological condition, with the exception of hydroxycarbamide to control white blood cell count 2. Other active malignancy requiring treatment 3. Newly diagnosed or uncontrolled HIV or hepatitis B or C infection. Patients with known chronic infections may enrol if the last two tests for viral load have been negative and their current therapy does not include a protease inhibitor or a non-nucleoside reverse-transcriptase inhibitor 4. Pregnant and lactating patients (patients of childbearing potential must have a negative pregnancy test prior to study entry) 5. Females of childbearing potential, and their partners, not willing to use adequate contraception during and for up to 6 months after treatment 6. Unable to swallow tablets whole 7. Known hypersensitivity to any of the IMPs 8. Patients known to require vaccination with a live vaccine during the treatment period
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Molecular event-free survival time (mEFS) is calculated as the time from date of randomisation to the date of the first recorded event, where an event is defined as follows: 1.1. Failure to achieve morphological CR or CRi after two cycles of therapy measured using blood and bone marrow tests 1.1.1. Morphological complete remission (CR): 1 log in a patient who previously tested negative in at least one technically adequate bone marrow sample (i.e. ABL Ct 1 log, confirmed on a second sample 1.3. Morphological relapse (=5% blasts in the blood or bone marrow in a patient with a previously documented CR, CRi or morphological leukaemia free state) 1.4. Death from any cause measured using patient records | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Occurrence of morphological complete remission (CR) by the end of the second cycle of treatment is evaluated from the morphological response assessments taken at the end of cycles 1 and 2 2. Death within 30 and 60 days from trial entry will include deaths from any cause and can only be evaluated in those patients who have been followed up for these periods of time 3. Overall survival time is calculated as the time from date of randomisation to date of death from any cause; patients alive at the time of analysis will be censored at their date last seen alive 4. Time to morphological relapse is calculated as the time from date of complete morphological remission to date when morphological relapse is first recorded 5. Time to molecular relapse is calculated as the time from date of molecular remission to date when molecular relapse is first recorded 6. Cumulative occurrence of grade 3 and 4 adverse events (AE) at 12 and 24 months is evaluated as the total number of grade 3 and 4 AE that are reported during these periods, from all AE that are reported and graded according to CTCAE criteria throughout the duration of the trial 7. Prevalence of molecular complete remission at month 3, 6 and 12 is evaluated from the molecular response assessments taken at these approximate time points from trial entry 8. Cumulative resource use at 12 and 24 months is calculated as total number of hospital admission days, total blood product usage and total number of days on intravenous antibiotics and antifungals that are reported for these periods of time from trial entry 9. Health-related quality of life (QoL) at month 3, 6, 12, 18 and 24 is evaluated from the EORTC QLQ-C30 and EQ-5D questionnaires completed by patients at clinic visits occurring at these approximate time points from trial entry; the questionnaires will yield 15 and 2 different measures of QoL respectively 10. Performance status evaluated by clinical assessment according to the Eastern Cooperative Oncology Group class | — |
Countries
England, Northern Ireland, Scotland, United Kingdom, Wales
Outcome results
None listed