Venetoclax or Intensive Chemotherapy for Treatment Of favourable Risk acute myeloid leukaemia: a molecularly guided phase 2 study
Acute myeloid leukaemia
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 will be randomised to receive either standard of care intensive chemotherapy (with cytarabine, daunorubicin and gemtuzumab ozogamicin (DAGO)) or venetoclax combined with cytarabine (VEN+LDAC- the experimental combination). The primary aim of the study is to compare the two treatment arms in terms of molecular event free survival (mEFS), which is defined as failure to achieve complete remission (or complete remission without recovered blood counts) after two cycles of treatment, molecular persistence (the disease is not responding to treatment), progression or relapse resulting in a treatment change (this will be assessed via bone marrow samples), relapse or death. The two treatment arms will also be compared in terms of toxicity (side effects), overall survival, time to response or disease progression, quality of life and resource use (number of transfusions, days in hospital and use of anti-infective medication). The aim is to demonstrate non-inferiority in the experimental arm- therefore to show that this arm is at least equivalent to the current standard of care in terms of treatment outcome. It is expected that this arm will be associated with less severe side effects and economic cost compared to standard chemotherapy. Venetoclax is already widely used in the treatment of other blood cancers such as chronic lymphocytic leukaemia and research studies so far have demonstrated impressive outcomes in AML NPM1 mutated patients who have received venetoclax in combination with another chemotherapy drug- such as cytarabine. This is the first trial directly comparing VEN+LDAC to standard of care chemotherapy (IC) in patients who are fit enough to receive chemotherapy. VICTOR will recruit 156 patients to be randomised 1:1 between the two treatment arms over two years. Patients
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 <=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 Previous inclusion criteria: 1. Diagnosis of CD33-positive acute myeloid leukaemia 2. Age >=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
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