Acute myeloid leukemia Cancer
Conditions
Interventions
Current interventions as of 09/06/2026:
Study arm 1: DA + Midostaurin
Therapy will consist of:
Course 1: DA60 3+10 + Midostaurin.
Daunorubicin IV 60mg/m2 OD on D1,3,5.
Sponsors
Cardiff University
Eligibility
Sex/Gender
All
Age
16 Years to 110 Years
Inclusion criteria
Inclusion criteria: Current key inclusion criteria as of 09/06/2026: 1. Diagnosis of AML 2. Age =16 years (no specified upper age limit) 3. Considered fit for intensive AML therapy by the treating physician 4. Confirmed FLT3 ITD or TKD mutation (or FLT3 status unknown but requires urgent therapy - see below*) 5. Serum creatinine less than or equal to 1.5 x ULN (upper limit of normal) 6. Serum Alanine Aminotransferase (ALT) OR Aspartate Aminotransferase (AST) less than or equal to 2.5 x ULN and bilirubin less than or equal to 2 x ULN 7. A negative pregnancy test within 2 weeks prior to trial entry in WOCBP (to be repeated throughout the trial prior to each course of protocol treatment) 8. Sexually mature males and females must agree to use an adequate and medically accepted method of contraception throughout the study and for 6 months following treatment if they or their sexual partners are women of childbearing potential (WOCBP) 9. WHO performance status 0-2 10. Written informed consent *FLT3-mutated AML is associated with proliferative disease features such as hyperleukocytosis (high white blood cell count) and may present as a medical emergency. It is important that the full clinical spectrum of FLT3-mutated AML is represented in Optimise-FLT3, including hyper-proliferative cases. Should the treating physician feel that the safety of an individual patient could be compromised by delaying therapy while awaiting FLT3 genotyping, they may, on discussion with the study team, proceed with study entry (using PIS2), randomisation and treatment provided all other eligibility criteria are met. Any patients who enter the trial and are subsequently found to have wild-type FLT3 will be considered evaluable for safety/toxicity analysis but will be replaced with additional FLT3-mutated cases to maintain statistical power for the clinical efficacy endpoints and equipoise between arms. Previous key inclusion criteria: 1. Diagnosis of AML 2. Age =16 years (no specified upper age limit) 3. Considered fit for intensive AML therapy by the treating physician 4. Confirmed FLT3 ITD or TKD mutation (or FLT3 status unknown but requires urgent therapy - see below*) 5. Serum creatinine less than or equal to 1.5 x ULN (upper limit of normal) 6. Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) less than or equal to 2.5 x ULN and bilirubin less than or equal to 2 x ULN 7. A negative pregnancy test within 2 weeks prior to trial entry in WOCBP (to be repeated throughout the trial prior to each course of protocol treatment) 8. Sexually mature males and females must agree to use an adequate and medically accepted method of contraception throughout the study and for 6 months following treatment if they or their sexual partners are women of childbearing potential (WOCBP) 9. WHO performance status 0-2 10. Written informed consent *FLT3-mutated AML is associated with proliferative disease features such as hyperleukocytosis (high white blood cell count) and may present as a medical emergency. It is important that the full clinical spectrum of FLT3-mutated AML is represented in Optimise-FLT3, including hyper-proliferative cases. Should the treating physician feel that the safety of an individual patient could be compromised by delaying therapy while awaiting FLT3 genotyping, they may, on discussion with the study team, proceed with study entry (using PIS2), randomisation and treatment provided all other eligibility criteria are met. Any patients who enter the
Exclusion criteria
Exclusion criteria: 1. Receipt of any previous therapy for AML or any antecedent haematological condition (the use of oral hydroxycarbamide to control white blood cell count is permitted) 2. Other active malignancy requiring treatment 3. Patients who are pregnant or lactating 4. Uncontrolled infection with Human Immunodeficiency Virus (HIV) or Hepatitis B or C. Patients with known chronic infections who are receiving or have completed therapy and have recent documented negative viral PCR tests are not excluded 5. Blast transformation of chronic myeloid leukaemia (CML)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Event-free survival (EFS) time, measured in days from the date of randomisation until the date of the first of any EFS events below. Patients still alive and event-free at the end of follow-up will be censored at the date of the most recent documented blood or bone marrow test that shows parameters consistent with ongoing disease response. Event data will be collected for the duration of follow-up until 2 years after the last patient has completed protocol treatment. Specified EFS events will include: 1. Death from any cause 2. Failure to achieve complete remission (CR), CR with partial hematologic recovery (CRh) or CR with incomplete count recovery (CRi) after two chemotherapy cycles 3. MRD relapse, as defined by the European Leukaemia Network Morphological and MRD remission status will be assessed by bone marrow aspiration following each cycle of chemotherapy in the context of recovery of peripheral blood count. MRD remission status is assessed by NPM1 qPCR (NPM1 co-mutated patients) and by flow cytometry in non-NPM1 co-mutated patients. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Incidence of complete remission (CR, CRh and CRi by ELN2022) within two cycles: morphological remission status assessed by repeat bone marrow aspiration following each cycle of chemotherapy in the context of recovery of peripheral blood count 2. Number of deaths within 30 and 60 days from randomisation 3. Overall survival time, measured in days from the date of randomisation until the date of death from any cause. Patients still alive at the end of follow-up will be censored at the date last seen in clinic (telephone confirmation will be acceptable). 4. Time to haematological relapse, measured from the date of documentation of 1st CR, CRi or CRh until the date of frank relapse. Patients who have not relapsed at the end of follow-up will be censored at the date of last documented blood or bone marrow test that shows parameters consistent with ongoing disease response. 5. The number and percentage of patients with MRD negativity after cycle 2 by RT-qPCR (for NPM1mut) or flow cytometry 6. Time to MRD relapse for patients with a monitored MRD marker, measured from the date of first molecular complete remission, until the date of MRD relapse (as defined by the ELN2022 23). Patients who are MRD negative will be censored at the date of last MRD assessment. 7. Cumulative incidence of grade 3 and 4 toxicity (by CTCAE version 5) over the duration of follow-up. The worst grade of toxicity will be reported. 8. Cumulative resource use including duration of hospital admissions, blood product usage (red cells, platelets) and days on intravenous antibiotics and antifungals. These measures will be collected following each cycle of intensive chemotherapy and compared by individual chemotherapy cycle and cumulatively by study arm 9. Rates of allogeneic stem cell transplant by study arm: in first remission and at later timepoints 10. Health-related quality of life assessed during treatment and over 2 years of post-treatment follow-up. Measured by EORTC QLQ-C30 and EQ-5D-5L followin | — |
Countries
Denmark, England, New Zealand, Northern Ireland, Scotland, United Kingdom
Outcome results
None listed