Acute Myeloid Leukaemia High Risk Myelodysplastic Syndrome MedDRA version: 20.0 Level: SOC Classification code 10005329 Term: Blood and lymphatic system disorders System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Product Name: AC220 (Quizartinib)
Pharmaceutical Form: Tablet
Trade Name: Mylotarg
Product Name: Mylotarg
Pharmaceutical Form: Powder for solution for infusion
Trade Name: LITAK
Product Name: LITAK
Sponsors
Cardiff University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients are eligible for the AML18 trial if: •They have one of the forms of acute myeloid leukaemia, except Acute Promyelocytic Leukaemia as defined by the WHO Classification (Appendix A) this can be any type of de novo or secondary AML – or high risk Myelodysplastic Syndrome, defined as greater than 10% marrow blasts (RAEB-2). (NB patients with prior MDS (>10% blasts, RAEB2) who have received prior azacitidine are not eligible for the trial, but patients with =65 years) yes F.1.3.1 Number of subjects for this age range 750
Exclusion criteria
Exclusion criteria: Patients are not eligible for the AML18 trial if: •They have previously received cytotoxic chemotherapy for AML [Hydroxycarbamide, or similar low-dose therapy, to control the white count prior to initiation of intensive therapy, is not an exclusion] •They are in blast transformation of chronic myeloid leukaemia (CML) •They have a concurrent active malignancy excluding basal cell carcinoma •They are pregnant or lactating •They have Acute Promyelocytic Leukaemia •Known infection with human immunodeficiency virus (HIV) •Patients with prior cumulative anthracycline exposure (from prior treatment of a non AML cancer) of greater than 300 mg/m2 daunorubicin (or equivalent). •History of myocardial infarction (MI), unstable angina, cerebrovascular accident, or transient ischemic attack (CVA/TIA) within 3 months before entry •Patients with known adverse risk cytogenetics are excluded from entering the AML18 trial unless they are registered to receive vosaroxin and decitabine Specific exclusion criteria for the Mylotarg Arm •Pre-existing liver impairment with known cirrhosis •Total bilirubin > 1.5 x the upper limit of normal (ULN) •Aspartate aminotransferase (AST) > 2.5 x ULN •Alanine aminotransferase (ALT) > 2.5 x ULN Specific exclusion criteria for the Vosaroxin/Decitabine Arm •Total bilirubin > 1.5 x the upper limit of normal (ULN), •Aspartate aminotransferase (AST) > 2.5 x ULN •Alanine aminotransferase (ALT) > 2.5 x ULN •Left ventricular ejection fraction (LVEF) 450 ms (average of triplicate ECG recordings); a consistent method of QTc calculation must be used for each patient’s QTc measurements. QTcF (Fridericia’s formula) is preferred. Please see the trial website for QTcF calculator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This trial will aim to answer the following questions: 1.Does CPX-351 given for 3 courses improve survival compared to the current standard of care of DA plus two doses of GO 3mg/m2 (maximum 5 mg per dose) for older patients with AML without known adverse risk cytogenetics? 2.Does the addition of either a short or long (maintenance) course of AC220 starting at course 2 after DA chemotherapy for patients with a FLT3 mutation in the diagnostic sample improve outcomes? 3.Is MRD status following course 1 of clinical value? In particular, can outcomes be improved by intensifying treatment in patients who show evidence of residual disease following course 1 of treatment? 4.To compare a further course of DA versus intermediate-dose Cytarabine in patients who are in CR or CRi and MRD -ve after induction course 1 and have received a second course of DA induction 5.In patients with known adverse risk cytogenetics (using Grimwade 2010 classification favourable/intermediate/adverse, see table 1 a;Secondary Objective: Blood and bone marrow will be collected at diagnosis, post course 1, during remission and at relapse to evaluate the therapeutic relevance of morphological, cytogenetic, molecular-genetic and immunophenotypic assessments, with particular respect to: 1)The relevance of the presence of a cytogenetic abnormality in the bone marrow of patients in morphological remission 2)The relevance of molecular characteristics and response to treatment 3)To store diagnostic tissue for future research in the AML Tissue Bank 4)To determine the predictive impact of the LSC17 gene signature on outcome of patients entering the two arms of the trial;Primary end point(s): The primary outcome measure will be: 1)Overall survival 2)Complete remission (CR + CRi) achievement and reasons for failure (for induction questions) 3)Duration of remission, relapse rates and deaths in first CR 4)Toxicity, both haematological and non-haematological 5)Supportive care requirements (and o | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Blood and bone marrow will be required at diagnosis, post course 1 during remission and at relapse to evaluate the therapeutic relevance of morphological, cytogenetic, molecular-genetic and immunophenotypic assessments, with particular respect to: •The relevance of the presence of a cytogenetic abnormality in the bone marrow of patients in morphological remission. •The relevance of molecular characteristics and response to treatment. •To store diagnostic tissue for future research in the AML Tissue Bank. •To determine the predictive impact of the LSC17 gene signature on outcome of patients entering the two arms of the trial | — |
Countries
Denmark, United Kingdom
Outcome results
None listed