Newly diagnosed secondary or high risk AML MedDRA version: 20.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Vyxeos
Product Name: Vyxeos
Product Code: CPX351
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: DAUNORUBICIN
CAS Number: 20830-81-3
Concentration unit: mg milli
Sponsors
Fundación PETHEMA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent in accordance with national, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure. Informed consent form must be signed by the patient and the investigator. 2. Age 60 to 75 years at the time of diagnosis of AML. 3. Newly confirmed diagnosed of AML according to WHO 2008 criteria. 4. Secondary or high risk AML, defined as one of the following: t-AML: documentation of prior cytotoxic therapy or radiation therapy for an unrelated disease in a discharge summary or pharmacy records or radiation therapy records. MDSAML: bone marrow documentation of MDS prior to diagnosis of AML (could have been treated previously with hypomethylating or standard chemotherapy). CMMoLAML: bone marrow documentation of CMMoL prior to diagnosis of AML (could have been treated previously with hypomethylating or standard chemotherapy). de novoAML with FISH or cytogenetic changes linked to MDS per WHO 2016 criteria. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. 6. Ability to adhere to the study visit schedule and other protocol requirements. 7. Laboratory values fulfilling the following: Serum creatinine =65 years) yes F.1.3.1 Number of subjects for this age range 39
Exclusion criteria
Exclusion criteria: 1. Patients with genetic diagnosis of acute promyelocytic leukemia. 2. Age 75 years. 3. Blastic phase of bcr/abl chronic myeloid leukemia. 4. Patients with de novo AML without FISH or cytogenetic changes linked to MDS per WHO 2016 criteria. 5. Clinical evidence of active central nervous system (CNS) leukemia. 6. Subjects with active (uncontrolled, metastatic) second malignancies. 7. Any major surgery or radiation therapy in 4 weeks. 8. Subjects with myocardial impairment of any cause (eg, cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, and congestive heart failure) resulting in heart failure by New York Heart Association Criteria (Class III or IV staging). 9. Uncontrolled infection; subjects with an infection receiving treatment (antibiotic, antifungal, or antiviral treatment) could be entered into the study provided the subject was respiratory and hemodynamically stable for = 72 hours. 10. Current evidence of invasive fungal infection (blood or tissue culture); subjects with recent fungal infection must have had subsequent negative cultures to be eligible; known HIV (new testing not required) or evidence of active hepatitis B or C infection (with rising transaminase values). 11. Hypersensitivity to cytarabine, daunorubicin or liposomal products. 12. Presence of any severe psychiatric disease or physical condition that, according to the physician´s criteria, contraindicates the inclusion of the patient into the clinical trial. 13. Serum creatinine = 20 mg/dL (unless it is attributable to AML activity). 14. Bilirubin, alkaline phosphatase, or SGOT > 3 times the ULN (unless it is attributable to AML activity). 15. Subjects with prior cumulative anthracycline exposure of greater than 368 mg/m2 daunorubicin (or equivalent). 16. History of Wilson’s disease or other copper-metabolism disorder. 17. Patients who have received an investigational agent (for any indication) within 5 half-lives of the agent and until toxicity from this has resolved to grade 1 or less; if the half-life of the agent is unknown, patients must wait 4 weeks prior to first dose of study treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the CR/CRi rate after induction with CPX-351;Secondary Objective: -To eval the safety/toxicity of CPX-351 induction reg -To eval the effect of priming with G-CSF with CPX-351 reg -To eval the safety/toxicity of CPX-351 consolid reg -To eval the safety/toxicity of CPX-351 maint reg -To assess the estimated 1, 2 and 3 year OS -To estimate 1, 2 and 3 years event-free, disease-free, and RFS, as well as on the duration of remission and cumulative incidence of relapse -To assess the overall hematologic and non-hemato toxicity -To eval the impact on the quality of life, using the EQ5D form, in patients treated with CPX-351 -To eval the impact on the use of medical resources during induction and consolid phase -To eval the quality of CR -To eval early mortality (first 60 days) in patients initially treated with CPX-351 -To compare the results with a matched-paired historical cohort of the PETHEMA registry -To assess the rate of allo-SCT -To eval 100 day mortality after allo-SCT -To assess the feasibility and compliance of the maint schedule;Primary end point(s): The primary endpoint of the study is to evaluate the CR/CRi rate after induction with CPX-351. The responses for CR, CRi, PR, therapeutic failure, and disease recurrence are defined for this study based on the revised recommendations of the International Working Group for response criteria. Efficacy analyses will be performed based on the FAS population (Full Analysis Set). If there are substantial differences in the FAS and the PPS (Per Protocol Set), the FAS efficacy analyses may be repeated on the PPS, as a complement to the FAS analyses. The primary efficacy endpoint is ORR (Objective Response Rate), which will be estimated by dividing the total number of patients in the FAS who achieve OR (Objective Response) by the total number of patients in the FAS. A 95% exact confidence interval for response rate will be provided, using Clopper-Pearson methodology. As is clear from the defini | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints will be described using Kaplan-Meier methodology. Point estimates and 95% confidence intervals for the median, 25th percentile, and 75th percentile of the distributions of each secondary endpoint will be provided. Secondary efficacy endpoints include: • Disease-free survival (DFS), defined as time from the first documentation of remission to the documentation of disease recurrence or death. • Event-free survival (EFS), defined as time from diagnosis to death, not response or relapse. • Overall survival (OS), defined as the number of days from diagnosis until death. The calculations for duration of remission and DFS will be based on disease recurrence as determined from bone marrow assessments. The "stop date" for these endpoints will be the date of the earliest bone marrow assessment establishing disease recurrence or the date of death, whichever occurs first. Safety analysis will be performed on the FAS, and will include the following: - The incidence, severity (rated according to the latest CTCAE version) duration, causality, seriousness and type of AE - Changes in clinical laboratory results - Deaths (including 30-day mortality) - SAEs (Serious Adverse Events) - Withdrawals due to AEs;Timepoint(s) of evaluation of this end point: The DFS, EFS and OS will be evaluated after 1, 2 and 3 years of treatment | — |
Countries
Spain
Contacts
Public ContactDr. Juan José Lahuerta Palacios
Fundación PETHEMA
Outcome results
None listed