Childhood de novo acute myeloid leukemia (AML)
Conditions
Interventions
Product Code: CPX-351
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Cytarabine
CAS Number: 147-94-4
Concentration unit: mg milligram(s)
Concentration type:
Sponsors
Children's Oncology Group
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - All patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part A) prior to enrollment and treatment on AAML1831 - Patients must be less than 22 years of age at the time of study enrollment - Patient must be newly diagnosed with de novo AML according to the 2016 World Health Organization (WHO) classification with or without extramedullary disease - Patient must have 1 of the following: • = 20% bone marrow blasts: In cases where extensive fibrosis may result in a dry tap, blast count can be obtained from touch imprints or estimated from an adequate bone marrow core biopsy. • =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients with the following constitutional conditions are not eligible. • Fanconi anemia • Shwachman Diamond syndrome • Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21 • Telomere disorders • Germline predispositions known, or suspected by the treating physician to increase risk of toxicity with AML therapy. Patients with any of the following oncologic diagnoses are not eligible. • Any concurrent malignancy • Juvenile myelomonocytic leukemia (JMML) • Philadelphia chromosome positive AML • Mixed phenotype acute leukemia • Acute promyelocytic leukemia • Acute myeloid leukemia arising from myelodysplasia • Therapy-related myeloid neoplasms Cardiac Function Patients with persistent cardiac dysfunction prior to enrollment, defined as ejection fraction (EF) < 50% (preferred method Biplane Simpson’s EF) or if EF unavailable, shortening fraction (SF) < 24%. *Note: if clinically safe and feasible, repeat echocardiogram is strongly advised in order to confirm cardiac dysfunction following clinical stabilization, particularly if occurring in the setting of sepsis or other transient physiologic stressor. If the repeat echocardiogram demonstrates an EF = 50%, the patient is eligible to enroll and may receive an anthracycline-containing Induction regimen. Prior Therapy Administration of prior anti-cancer therapy except as outlined below: • Hydroxyurea • All-trans retinoic acid (ATRA) • Corticosteroids (any route) • Intrathecal therapy given at diagnosis Pregnancy and Breastfeeding • Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential. • Lactating females who plan to breastfeed their infants. • Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation. Regulatory Requirements • All patients and/or their parents or legal guardians must sign a written informed consent. • All institutional, FDA, and NCI requirements for human studies must be met.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare EFS in children with de novo AML without FLT3 mutations who are randomly assigned to standard induction therapy with DA and GO (Arm A [DA-GO]) versus induction therapy with CPX-351 and GO (Arm B [CPX-351-GO]).;Secondary Objective: - To compare OS and rates of EOI1 MRD in children with de novo AML without FLT3 mutations who are randomly assigned to standard induction therapy with DA-GO versus induction therapy with CPX-351 and GO - To compare the incidence of significant LVSD in children with de novo AML without FLT3 mutations who are randomly assigned to standard induction therapy with DA-GO versus CPX-351 and GO - To compare the changes in echocardiography-derived measures of cardiac function, including left ventricular EF and GLS, throughout AML therapy in patients with LR and HR AML without FLT3 mutations receiving Arm A vs Arm B - Determine if early changes in sensitive echocardiographic measures of cardiac function (ie, post-Induction 1 decline in GLS) and elevations in circulating cardiac biomarkers (ie, cardiac troponin T and N-terminal pro b-type natriuretic peptide) are associated with subsequent declines in left ventricular EF in patients with non-FLT3–mutant AML receiving therapy on Arms A or Arm B;Primary end point(s): Event-free survival (EFS);Timepoint(s) of evaluation of this end point: Up to 3 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? Overall survival (OS) ? Proportion of patients positive for minimal residual disease (MRD+) at end of induction 1 (EOI1) ? Course duration ? Length of hospitalization ? Time to Count Recovery ? Relapse rate ? Treatment-related mortality rate ? Incidence of significant left ventricular systolic dysfunction ? Changes in Echocardiography-Derived Measures of Cardiac Function ;Timepoint(s) of evaluation of this end point: ? Up to 3 years ? Up to 4 weeks ? Up to 2 years ? Up to 2 years ? Up to 2 years ? Up to 3 years ? Up to 3 years ? Up to 3 years ? Up to 3 years | — |
Countries
Australia, Canada, United States
Contacts
Public ContactClinical Trial Disclosure
Jazz Pharmaceuticals
Outcome results
None listed