Newly diagnosed Acute Myeloid Leukaemia Cancer
Conditions
Interventions
The ACT-AML-901 study is a prospective, multi-centre, two-part open-label, Phase I/II, 2:1 randomized study comparing tagraxofusp, venetoclax, cytarabine and cladribine combination therapy with the cu
Sponsors
Didact Foundation
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. Adverse risk AML according to European Leukaemia Net (ELN) 2022 criteria (Döhner, et al., 2022), aged 18 years or older 2. Intermediate risk AML according to ELN 2022 criteria (Döhner, et al., 2022), aged 50 years or older 3. Evidence of CD123 expression on myeloid blast population 4. The participant is deemed by the treating physician to be fit for intensive chemotherapy 5. Eastern Cooperative Oncology Group (ECOG) performance status 0–2 6. Adequate renal, liver, and cardiac function 7. Participant agrees to use an adequate and medically accepted method of contraception throughout the study and for the required contraceptive period if they or their sexual partner are female-born of childbearing potential 8. Negative pregnancy test within 2 weeks prior to randomisation
Exclusion criteria
Exclusion criteria: Current key exclusion criteria as of 06/02/2026: 1. Have received previous cytotoxic chemotherapy (intensive or non-intensive), targeted therapies, hypomethylating agents, or venetoclax for the treatment of AML — except: 1.1. Hydroxycarbamide to control elevated white blood cell (WBC) count 1.2. Lenalidomide, Imetelstat, or luspatercept for the treatment of Myelodysplasia 2. Blastic transformation of chronic myeloid leukaemia (CML) 3. Clinical suspicion of active central nervous system (CNS) involvement with AML 4. Presence of a FLT3-ITD mutation or an NPM1 mutation during initial rapid diagnostic evaluation 5. Presence of a concurrent malignancy requiring active treatment (see Section 4.2 for exceptions) 6. Diagnosis of acute promyelocytic leukaemia (APL) 7. Known active, chronic or uncontrolled infections with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) 8. Significant disease or medical conditions, as assessed by the Investigator, which would substantially increase the risk-benefit ratio of participating in the study, including but not limited to: 8.1. History of myocardial infarction within 6 months of randomisation 8.2. Presence of unstable angina, cerebrovascular accident (CVA), transient ischemic attack (TIA), uncontrolled diabetes mellitus, significant active infections, and congestive heart failure (NYHA Class III–IV) within 3 months of randomisation 9. History of Wilson’s disease or other copper-metabolism disorder 10. Pre-existing liver impairment with known cirrhosis 11. History of any of the following: drug-induced severe cutaneous adverse reaction (SCAR) including, but not limited to, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), or drug reaction with eosinophilia and systemic symptoms (DRESS), or dose-limiting immune-mediated reactions 12. Active infection, recently exposed to, or existing chicken pox or herpes zoster infection 13. Judgement by the local Investigator that the participant should not participate in the study, if the participant is unlikely to comply with study procedures, restrictions and requirements 14. Concomitant use of: 14.1. Any strong or moderate CYP3A inhibitors, except posaconazole or voriconazole 14.2. Note that participants subsequently enrolled/randomised to Part 1/Part 2 Arm B would be required to discontinue voriconazole, and instead receive posaconazole, prior to commencing treatment with VEN 14.3. Any strong or moderate CYP3A inducers 14.4. Preparations containing St John’s Wort 15. Pregnant or lactating participants 16. Female-born participants of childbearing potential, or male-born participants with female partners of childbearing potential, not willing to use adequate contraception during study treatment and for the required contraceptive periods 17. Participants who are unable to swallow tablets whole 18. Unable to understand and therefore to give voluntary consent 19. Known hypersensitivity to any of the IMPs, the metabolites or formulation excipients 20. Current participation in another interventional clinical study. Participants in follow-up who have not received the interventional treatment within 4 weeks of enrolment/randomisation may enrol. 21. Participants receiving any live vaccine within 4 weeks prior to initiation of study treatments 22. Participants known to require vaccination with a live vaccine during the treatment period or for 3 months after the end of study treatment 23. Participants who
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Superiority of the tagraxofusp, venetoclax, cladribine, cytarabine combination therapy versus standard of care intensive chemotherapy as measured by event free survival (EFS). The planned primary analysis will take place when 115 EFS events have occurred, or all patients have been followed for a minimum of 1 year, which is expected to occur approximately 30 months from the date of randomisation of the first patient into the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety, efficacy and tolerability of TAG/CLAD/VEN/LDAC combination therapy (experimental arm) versus standard of care IC (control arm) as measured by: 1. Overall Survival 2. Complete response (CR) 3. Composite CR (CR/CRi) rate 4. The overall response rate (defined as the proportion of patients with either CR, CRi, or morphologic leukaemia-free state [MLFS]) 5. Proportion of participants achieving MRD negativity (CRMRD-) 6. Duration of CR 7. Duration of CR/CRi 8. Day 60 treatment-related mortality 9. Incidence of > CTCAE Grade 3 non-haematological adverse events (AEs) 10. Duration of hospitalisation in participants prior to allo-SCT 11. Proportion of participants proceeding to allo-SCT 12. Day 100 transplant-related mortality (TRM) in participants proceeding to allograft 13. 2-year overall survival (OS) and 2-year relapse-free survival (RFS) in allografted participants 14. 2-year cumulative incidence of relapse (CIR) in allografted participants 15. Transfusion independence 16. Time to transfusion independence 17. Health-related QoL throughout the study | — |
Countries
England, United Kingdom
Contacts
Public ContactSusie Brown
Outcome results
None listed