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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04293562




Registration number
NCT04293562
Ethics application status
Date submitted
18/02/2020
Date registered
3/03/2020
Date last updated
22/04/2024

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
NCI-2020-00546
Secondary ID [2] 0 0
AAML1831
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Allogeneic Hematopoietic Stem Cell Transplantation
Treatment: Drugs - Asparaginase
Treatment: Drugs - Asparaginase Erwinia chrysanthemi
Treatment: Surgery - Biospecimen Collection
Treatment: Surgery - Bone Marrow Aspiration
Treatment: Surgery - Bone Marrow Biopsy
Behaviour - Cogstate Assessment Battery
Treatment: Surgery - Computed Tomography
Treatment: Drugs - Cytarabine
Treatment: Drugs - Daunorubicin Hydrochloride
Treatment: Drugs - Dexrazoxane Hydrochloride
Treatment: Drugs - Etoposide
Other interventions - Fludeoxyglucose F-18
Treatment: Drugs - Gemtuzumab Ozogamicin
Treatment: Drugs - Gilteritinib Fumarate
Treatment: Drugs - Liposome-encapsulated Daunorubicin-Cytarabine
Treatment: Surgery - Magnetic Resonance Imaging
Treatment: Drugs - Methotrexate
Treatment: Drugs - Mitoxantrone Hydrochloride
Treatment: Surgery - Positron Emission Tomography
Treatment: Drugs - Therapeutic Hydrocortisone

Experimental: Arm A High Risk Group - Arm A High Risk Group: See Detailed Description.

Experimental: Arm A Low Risk Group 1 - Arm A Low Risk Group 1: See Detailed Description.

Experimental: Arm A Low Risk Group 2 - Arm A Low Risk Group 2: See Detailed Description.

Experimental: Arm AC High Risk Group - Arm AC High Risk Group: See Detailed Description.

Experimental: Arm AC Low Risk Group 2 - Arm AC Low Risk Group 2: See Detailed Description.

Experimental: Arm AD High Risk Group - Arm AD High Risk Group: See Detailed Description.

Experimental: Arm AD Low Risk Group 2 - Arm AD Low Risk Group 2: See Detailed Description.

Experimental: Arm B High Risk Group - Arm B High Risk Group: See Detailed Description.

Experimental: Arm B Low Risk Group 1 - Arm B Low Risk Group 1: See Detailed Description.

Experimental: Arm B Low Risk Group 2 - Arm B Low Risk Group 2: See Detailed Description.

Experimental: Arm BC High Risk Group - Arm BC High Risk Group: See Detailed Description.

Experimental: Arm BC Low Risk Group 2 - Arm BC Low Risk Group 2: See Detailed Description.

Experimental: Arm BD High Risk Group - Arm BD High Risk Group: See Detailed Description.

Experimental: Arm BD Low Risk Group 2 - Arm BD Low Risk Group 2: See Detailed Description.


Treatment: Surgery: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic HSCT

Treatment: Drugs: Asparaginase
Given IM or IV

Treatment: Drugs: Asparaginase Erwinia chrysanthemi
Given IM or IV

Treatment: Surgery: Biospecimen Collection
Correlative studies

Treatment: Surgery: Bone Marrow Aspiration
Undergo BM aspiration

Treatment: Surgery: Bone Marrow Biopsy
BM biopsy

Behaviour: Cogstate Assessment Battery
Ancillary studies

Treatment: Surgery: Computed Tomography
Undergo CT

Treatment: Drugs: Cytarabine
Given IV or IT

Treatment: Drugs: Daunorubicin Hydrochloride
Given IV

Treatment: Drugs: Dexrazoxane Hydrochloride
Given IV

Treatment: Drugs: Etoposide
Given IV

Other interventions: Fludeoxyglucose F-18
Undergo FDG-PET

Treatment: Drugs: Gemtuzumab Ozogamicin
Given IV

Treatment: Drugs: Gilteritinib Fumarate
Given PO/NG/G-tube

Treatment: Drugs: Liposome-encapsulated Daunorubicin-Cytarabine
Given IV

Treatment: Surgery: Magnetic Resonance Imaging
Undergo MRI

Treatment: Drugs: Methotrexate
Given IT

Treatment: Drugs: Mitoxantrone Hydrochloride
Given IV

Treatment: Surgery: Positron Emission Tomography
Undergo FDG-PET

Treatment: Drugs: Therapeutic Hydrocortisone
Given IT
Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Behaviour
Intervention code [4] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-free survival (EFS)
Timepoint [1] 0 0
Up to 3 years
Secondary outcome [1] 0 0
Overall survival (OS)
Timepoint [1] 0 0
Up to 3 years
Secondary outcome [2] 0 0
Proportion of patients positive for minimal residual disease (MRD+)
Timepoint [2] 0 0
Up to 4 weeks
Secondary outcome [3] 0 0
Proportion of patients who died during protocol therapy
Timepoint [3] 0 0
Up to 2 years
Secondary outcome [4] 0 0
Incidence of adverse events
Timepoint [4] 0 0
Up to 2 years
Secondary outcome [5] 0 0
Relapse rate
Timepoint [5] 0 0
Up to 3 years
Secondary outcome [6] 0 0
Treatment-related mortality rate (TRM)
Timepoint [6] 0 0
Up to 3 years

Eligibility
Key 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

- 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
associated with childhood/young adult AML as provided in the protocol
(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
Minimum age
No limit
Maximum age
21 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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

- 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

- 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

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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/07/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/09/2027
Actual
Sample size
Target
1400
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Connecticut
Country [7] 0 0
United States of America
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Delaware
Country [8] 0 0
United States of America
State/province [8] 0 0
District of Columbia
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United States of America
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Florida
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United States of America
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Georgia
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Hawaii
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Idaho
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Illinois
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Indiana
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Iowa
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Kentucky
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Louisiana
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Maine
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Mississippi
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Missouri
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Nebraska
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Nevada
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New Hampshire
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New Jersey
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New Mexico
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New York
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North Carolina
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North Dakota
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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Rhode Island
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South Carolina
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South Dakota
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Tennessee
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Utah
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Vermont
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Virginia
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Washington
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West Virginia
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Wisconsin
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Canada
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Alberta
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Canada
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British Columbia
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Canada
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Manitoba
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Canada
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Nova Scotia
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Ontario
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Quebec
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Canada
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Saskatchewan
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Puerto Rico
State/province [55] 0 0
San Juan

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This phase III trial compares standard chemotherapy to therapy with liposome-encapsulated
daunorubicin-cytarabine (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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04293562
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Todd M Cooper
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries