Title
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

Description
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

Objective
The overall goals of this study are to:

Compare the effects, good and/or bad, of CPX-351 with daunorubicin and cytarabine on people with newly diagnosed AML to find out which is better. In this study, you will get either the CPX-351 or daunorubicin and cytarabine. You will not get both

To study the effects, good and/or bad, of adding gilteritinib to AML therapy for patients with high amounts of FLT3/ITD or other FLT3 mutations

To study changes in heart function during and after treatment for AML

Treatment All patients will be randomized to receive treatment with the standard chemotherapy daunorubicin/cytarabine + Gemtuzumab Ozogamicin GO (Arm A) or treatment with CPX-351 + Gemtuzumab Ozogamicin GO (Arm B)

Key Eligibility
All patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part A) prior to enrollment and treatment on AAML1831

Must be less than 22 years of age at the time of study enrollment

Must be newly diagnosed with de novo AML according to the 2016 WHO classification with or without extramedullary disease

Must have 1 of the following: greater than or equal to 20 percent bone marrow blasts, less than 20 percent bone marrow blasts with one or more of the genetic abnormalities listed in the protocol, A complete blood count (CBC) documenting the presence of at least 1,000/uL (i.e., a WBC count greater than or equal to 10,000/uL with greater than or equal to 10 percent blasts or a WBC count of greater than or equal to 5,000/uL with greater than or equal to 20 percent blasts) circulating leukemic cells (blasts) if a bone marrow aspirate or biopsy cannot be performed

EXCLUSION

Myeloid neoplasms with germline predisposition are not eligible

Fanconi anemia

Shwachman Diamond syndrome

Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21

Any other known bone marrow failure syndrome

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

Administration of prior anti-cancer therapy except as outlined below: Hydroxyurea, All-trans retinoic acid (ATRA), Corticosteroids (any route), Intrathecal therapy given at diagnosis

Can not be pregnant or breastfeeding

Applicable Disease Sites
Leukemia

Participating Institutions
Gundersen Health System; UW Health University Hospital