Print this page

A Phase 3 Randomized Trial for Patients with de novo AML Comparing Standard Therapy Including Gemtuzumab Ozogamicin (GO) to CPX-351 with GO, and the Addition of the FLT3 Inhibitor Gilteritinib for Patients with FLT3 Mutations.

1. To compare event-free survival (EFS) in children with de novo AML without FLT3 mutations who are randomly assigned to standard induction therapy on Arm A (DA-GO) with daunorubicin, cytarabine (DA) and gemtuzumab ozogamicin (GO) versus Arm B with CPX-351 and GO.

2. To compare overall survival (OS) and rates of end of Induction 1 (EOI1) minimal residual disease (MRD) in children with de novo AML without FLT3 mutations who are randomly assigned to standard induction therapy (Arm A) with DA-GO versus CPX-351 and GO (Arm B).

3. To estimate the EFS and rate of EOI1 MRD in FLT3 internal tandem duplication mutation positive patients (FLT3/ITD+; as defined by allelic ratio > 0.1) without favorable cytomolecular characteristics (NPM1 and/or CEBPA) receiving gilteritinib in combination with DA GO (Arm AC).

4. To estimate the EFS and rate of EOI1 MRD in patients with non-ITD FLT3 activating mutations who receive backbone therapy (DA-GO or CPX-351 and GO) with gilteritinib (Arms AD and BD).

5. To determine the feasibility of combining gilteritinib and DA-GO or CPX-351 and GO in patients with FLT3/ITD mutations (Arm AC/Arm BC/Arm AD/Arm BD).

6. To compare EOI1 MRD and EFS in patients with FLT3/ITD AML+ (AR > 0.1) without favorable cytogenetic/molecular characteristics treated with DA-GO-gilteritinib vs CPX-GO-gilteritinib (Arm AC vs Arm BC).

7. To compare the incidence of significant left ventricular systolic dysfunction (LVSD) in children with de novo AML without FLT3 mutations who are randomly assigned to standard induction therapy (Arm A) with DA-GO versus CPX-351 and GO (Arm B).

8. To compare the changes in echocardiography-derived measures of cardiac function, including left ventricular ejection fraction (EF) and global longitudinal strain (GLS), throughout AML therapy in patients with low and high risk AML without FLT3 mutations receiving Arm A vs Arm B.

9. Determine if early changes in sensitive echocardiographic measures of cardiac function (i.e., post-Induction 1 decline in GLS) and elevations in circulating cardiac biomarkers (i.e., cardiac troponin T and N-terminal pro b-type natriuretic peptide) are associated with subsequent declines in left ventricular ejection fraction in patients with non-FLT3 mutant AML receiving therapy on Arms A or B.

10. To compare longitudinal acute changes in neuropsychological functioning and neurocognitive late effects between those with CNS disease and those without CNS disease and between those treated with HSCT and those treated with chemotherapy only for patients on Arms A and B.

11. To compare cardiotoxicity measures (EF, GLS, and cardiac biomarkers) in patients receiving standard induction with dexrazoxane vs. CPX-351 in the context of gilteritinib therapy and explore whether the differential cardiotoxicity across arms varies from that observed in non-FLT3 mutant AML without gilteritinib exposure.

12. To estimate the EFS and rate of EOI1 MRD in patients with high allelic ratio (HAR) FLT3/ITD+ patients, as historically defined by an AR > 0.4, receiving gilteritinib in combination with DA-GO (Arm AC with AR > 0.4).

13. To estimate the EFS and rate of EOI1 MRD in FLT3/ITD+ patients (as defined by allelic ratio > 0.1) with NPM1 and/or bZIP CEBPA mutations receiving gilteritinib in combination with DA-GO (Arm AC).

14. Compare the changes in high sensitivity troponin and natriuretic peptide elevations throughout AML therapy, as measured at the end of each chemotherapy course,
in patients with low and high risk AML without FLT3 mutations receiving Arm A vs Arm B

Protocol Number: 112008
Phase: Phase III
Applicable Disease Sites: Leukemia, not otherwise specified
Drugs Involved: CPX-351
Gilteritinib
Scope: National
Therapies Involved: Chemotherapy multiple agents systemic
Participating Institutions:
  • Rutgers Cancer Institute of New Jersey
    • Principal Investigator
      • Marissa Botwinick MD
  • RWJBarnabas Health
    • Newark Beth Israel Medical Center
Inclusion & Exclusion Criteria

Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.

For further information about clinical trials, please contact us at 732-235-7356.