Overview

A Study to Compare Standard Chemotherapy to Therapy With CPX-351 and/or Gilteritinib for Patients With Newly Diagnosed AML With or Without FLT3 Mutations

Status:
Recruiting
Trial end date:
2027-09-30
Target enrollment:
0
Participant gender:
All
Summary
This phase III trial compares standard chemotherapy to therapy with CPX-351 and/or gilteritinib for patients with newly diagnosed acute myeloid leukemia with or without FLT3 mutations. Drugs used in chemotherapy, such as daunorubicin, cytarabine, and gemtuzumab ozogamicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. CPX-351 is made up of daunorubicin and cytarabine and is made in a way that makes the drugs stay in the bone marrow longer and could be less likely to cause heart problems than traditional anthracycline drugs, a common class of chemotherapy drug. Some acute myeloid leukemia patients have an abnormality in the structure of a gene called FLT3. Genes are pieces of DNA (molecules that carry instructions for development, functioning, growth and reproduction) inside each cell that tell the cell what to do and when to grow and divide. FLT3 plays an important role in the normal making of blood cells. This gene can have permanent changes that cause it to function abnormally by making cancer cells grow. Gilteritinib may block the abnormal function of the FLT3 gene that makes cancer cells grow. The overall goals of this study are, 1) 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, 2) 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 and 3) to study changes in heart function during and after treatment for AML. Giving CPX-351 and/or gilteritinib with standard chemotherapy may work better in treating patients with acute myeloid leukemia compared to standard chemotherapy alone.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Children's Oncology Group
Collaborator:
National Cancer Institute (NCI)
Treatments:
3,6-bis(5-chloro-2-piperidyl)-2,5-piperazinedione
Asparaginase
Calicheamicins
Cytarabine
Daunorubicin
Dexrazoxane
Etoposide
Etoposide phosphate
Gemtuzumab
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone hemisuccinate
Methotrexate
Mitoxantrone
Podophyllotoxin
Razoxane
Criteria
Inclusion Criteria:

- All patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part
A) prior to enrollment and treatment on AAML1831. Submission of diagnostic specimens
must be done according to the Manual of Procedures). Risk stratification will not be
possible without the submission of viable samples. Given there are multiple required
samples, bone marrow acquisition techniques such as frequent repositioning or
performing bilateral bone marrow testing should be considered to avoid insufficient
material for required studies. Consider a repeat marrow prior to starting treatment if
there is insufficient diagnostic material for the required studies

- 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 (obtained within 14 days prior to enrollment)

- 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

- < 20% bone marrow blasts with one or more of the genetic abnormalities
(sample obtained within 14 days prior to enrollment)

- A complete blood count (CBC) documenting the presence of at least 1,000/uL
(i.e., a white blood cell [WBC] count >= 10,000/uL with >= 10% blasts or a
WBC count of >= 5,000/uL with >= 20% blasts) circulating leukemic cells
(blasts) if a bone marrow aspirate or biopsy cannot be performed (performed
within 7 days prior to enrollment)

- ARM C: Patient must be >= 2 years of age at the time of Late Callback

- ARM C: Patient must have FLT3/ITD allelic ratio > 0.1 as reported by Molecular
Oncology

- ARM C: Patient does not have any congenital long QT syndrome or congenital heart block

- ARM C: Females of reproductive potential must agree to use effective contraception
during treatment and for at least 6 months after the last dose of gilteritinib

- ARM C: Lactating women must agree not to breastfeed during treatment with gilteritinib
and for 2 months after the last dose of gilteritinib

- ARM C: Males of reproductive potential must agree to use effective contraception
during treatment and for at least 4 months after the last dose of gilteritinib

- ARM D: Patient must be >= 2 years of age at the time of Late Callback

- ARM D: Patient must have one of the clinically relevant non-ITD FLT3 activating
mutations as reported by Foundation Medicine

- ARM D: Females of reproductive potential must agree to use effective contraception
during treatment and for at least 6 months after the last dose of gilteritinib

- ARM D: Lactating women must agree not to breastfeed during treatment with gilteritinib
and for 2 months after the last dose of gilteritinib

- ARM D: Males of reproductive potential must agree to use effective contraception
during treatment and for at least 4 months after the last dose of gilteritinib

- NEUROPSYCHOLOGICAL TESTING: Patient must be enrolled on Arm A or Arm B. Patients who
transfer to Arm C or Arm D are not eligible

- NEUROPSYCHOLOGICAL TESTING: Patient must be 5 years or older at the time of enrollment

- NEUROPSYCHOLOGICAL TESTING: English-, French- or Spanish-speaking

- NEUROPSYCHOLOGICAL TESTING: No known history of neurodevelopmental disorder prior to
diagnosis of AML (e.g., Down syndrome, fragile X, William syndrome, mental
retardation)

- NEUROPSYCHOLOGICAL TESTING: No significant visual or motor impairment that would
prevent computer use or recognition of visual test stimuli

- All patients and/or their parents or legal guardians must sign a written informed
consent

- All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met.

Exclusion Criteria:

- Patients with 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

- In particular, strong inducers of CYP3A4 and/or P-glycoprotein (P-gp) should be
avoided from the time of enrollment until it is determined whether the patient
will receive gilteritinib. Patients receiving gilteritinib will be required to
avoid strong CYP3A4 inducers and/or strong P-gp inducers for the duration of the
study treatment

- 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

- ARM D: Patients with congenital long QT syndrome or congenital heart block are not
eligible for this treatment arm