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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/NCT01371981
Registration number
NCT01371981
Ethics application status
Date submitted
10/06/2011
Date registered
13/06/2011
Date last updated
21/05/2024
Titles & IDs
Public title
Bortezomib and Sorafenib Tosylate in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
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Scientific title
A Phase III Randomized Trial for Patients With De Novo AML Using Bortezomib and Sorafenib (NSC# 681239, NSC# 724772) for Patients With High Allelic Ratio FLT3/ITD
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Secondary ID [1]
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NCI-2011-02670
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Secondary ID [2]
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NCI-2011-02670
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia
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Leukemia Cutis
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Myeloid Neoplasm
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Myeloid Sarcoma
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Condition category
Condition code
Cancer
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0
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Leukaemia - Acute leukaemia
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Cancer
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0
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0
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Leukaemia - Chronic leukaemia
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Cancer
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0
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0
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Children's - Leukaemia & Lymphoma
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Cancer
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Sarcoma (also see 'Bone') - soft tissue
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Asparaginase
Treatment: Drugs - Bortezomib
Treatment: Drugs - Cytarabine
Treatment: Drugs - Daunorubicin Hydrochloride
Treatment: Drugs - Etoposide
Other interventions - Laboratory Biomarker Analysis
Treatment: Drugs - Mitoxantrone Hydrochloride
Other interventions - Pharmacological Study
Other interventions - Quality-of-Life Assessment
Other interventions - Questionnaire Administration
Treatment: Drugs - Sorafenib Tosylate
Experimental: Arm A - See Detailed Description
Experimental: Arm B - See Detailed Description
Experimental: Arm C (Cohort 1) - See Detailed Description
Experimental: Arm C (Cohort 2) - See Detailed Description.
Experimental: Arm C (Cohort 3) - See Detailed Description. Different dose.
Experimental: Arm D - See Detailed Description. May reassigned to Arm C.
Treatment: Drugs: Asparaginase
Given IM
Treatment: Drugs: Bortezomib
Given IV
Treatment: Drugs: Cytarabine
Given IT or IV
Treatment: Drugs: Daunorubicin Hydrochloride
Given IV
Treatment: Drugs: Etoposide
Given IV
Other interventions: Laboratory Biomarker Analysis
Correlative studies
Treatment: Drugs: Mitoxantrone Hydrochloride
Given IV
Other interventions: Pharmacological Study
Correlative studies
Other interventions: Quality-of-Life Assessment
Ancillary studies
Other interventions: Questionnaire Administration
Ancillary studies
Treatment: Drugs: Sorafenib Tosylate
Given PO
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Intervention code [1]
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Treatment: Drugs
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Intervention code [2]
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Other interventions
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Event-free Survival (EFS) for Patients Without High Allelic Ratio FLT3/ITD+ Mutations
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Assessment method [1]
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The Kaplan-Meier method will be used to estimate 3-year EFS, defined as the time from study entry until induction failure, relapse, secondary malignancy, or death.
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Timepoint [1]
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Up to 3 years
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Primary outcome [2]
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EFS for Patients on Arm C, Cohort 1
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Assessment method [2]
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The Kaplan-Meier method will be used to estimate 3-year EFS, defined as the time from study entry until induction failure, relapse, secondary malignancy, or death.
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Timepoint [2]
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Up to 3 years
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Primary outcome [3]
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EFS for Patients on Arm C, Cohort 2
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Assessment method [3]
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The Kaplan-Meier method will be used to estimate 3-year EFS, defined as the time from study entry until induction failure, relapse, secondary malignancy, or death.
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Timepoint [3]
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Up to 3 years
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Primary outcome [4]
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EFS for Patients on Arm C, Cohort 3
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Assessment method [4]
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The Kaplan-Meier method will be used to estimate 3-year EFS, defined as the time from study entry until induction failure, relapse, secondary malignancy, or death.
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Timepoint [4]
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Up to 3 years
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Secondary outcome [1]
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Overall Survival (OS) for Patients Without High Allelic Ratio FLT3/ITD+ Mutations
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Assessment method [1]
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The Kaplan-Meier method will be used to estimate 3-year OS, defined as the time from study entry until death.
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Timepoint [1]
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Up to 3 years
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Secondary outcome [2]
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OS for Patients on Arm C, Cohort 1
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Assessment method [2]
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The Kaplan-Meier method will be used to estimate 3-year OS, defined as the time from study entry until death.
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Timepoint [2]
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Up to 3 years
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Secondary outcome [3]
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OS for Patients on Arm C, Cohort 2
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Assessment method [3]
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The Kaplan-Meier method will be used to estimate 3-year OS, defined as the time from study entry until death.
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Timepoint [3]
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Up to 3 years
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Secondary outcome [4]
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OS for Patients on Arm C, Cohort 3
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Assessment method [4]
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The Kaplan-Meier method will be used to estimate 3-year OS, defined as the time from study entry until death.
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Timepoint [4]
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Up to 3 years
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Secondary outcome [5]
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Relapse Rate for Patients Without High Allelic Ratio FLT3/ITD+ Mutations
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Assessment method [5]
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Cumulative incidence estimates 3 year relapse rate defined as time from study entry to induction failure or relapse where deaths or secondary malignancies are competing events.
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Timepoint [5]
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Up to 3 years
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Secondary outcome [6]
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Proportion of Patients Experiencing Grade 3 or Higher Non-hematologic Toxicities and Infections While on Protocol Therapy
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Assessment method [6]
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The proportion of patients experiencing at least one grade 3 or higher non-hematologic toxicity and infection while on protocol therapy will be estimated along with the corresponding 95% confidence interval determined using a binomial exact method. Toxicity will be assessed by Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).
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Timepoint [6]
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Up to 2 years
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Secondary outcome [7]
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Proportion of High Risk Children Without HR FLT3/ITD+ Converting From Positive MRD at End of Induction I to Negative MRD at the End of Induction II
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Assessment method [7]
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The proportion of high risk children without HR FLT3/ITD+ converting from positive MRD at end of Induction I to negative MRD at the end of Induction II will be estimated as well as the corresponding 95% confidence interval determined using a binomial exact method.
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Timepoint [7]
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Up to 8 weeks
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Secondary outcome [8]
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Total Scale Score From Parent-reported Pediatric Quality of Life Inventory Module
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Assessment method [8]
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Results represent the total scale scores from the parent report of the PedsQL™ 4.0 Generic Core Scales for timepoint 1 (up to 14 days from start of therapy). Items are reverse-scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Therefore, a higher number is a better outcome. The total score is the sum of all the items divided by the number of items answered on all the scales. "Scores on a scale" is used for a unit of measure.
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Timepoint [8]
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Up to 14 days
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Secondary outcome [9]
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Total Scale Score From Parent-reported Cancer Module
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Assessment method [9]
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Results represent the total scale scores from the parent report of the PedsQL™ 3.0 Cancer Module for timepoint 1 (up to 14 days from start of therapy). Items are reverse-scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Therefore, a higher number is a better outcome. The total score is the sum of all the items divided by the number of items answered on all the scales. "Scores on a scale" is used for a unit of measure.
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Timepoint [9]
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Up to 14 days
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Secondary outcome [10]
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Total Scale Score From Parent-reported Multidimensional Fatigue Scale Module
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Assessment method [10]
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Results represent the total scale scores from the parent report of the PedsQL™ Multidimensional Fatigue Scale for timepoint 1 (up to 14 days from start of therapy). Items are reverse-scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Therefore, a higher number is a better outcome. The total score is the sum of all the items divided by the number of items answered on all the scales. "Scores on a scale" is used for a unit of measure.
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Timepoint [10]
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Up to 14 days
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Secondary outcome [11]
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Bortezomib Clearance
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Assessment method [11]
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Median and range of bortezomib clearance during Induction II.
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Timepoint [11]
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Day 8 of Induction II
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Secondary outcome [12]
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Sorafenib Steady State Concentration
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Assessment method [12]
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Median and range of sorafenib steady state concentration for Induction I.
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Timepoint [12]
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Up to 30 days
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Secondary outcome [13]
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Change in Shortening Fraction
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Assessment method [13]
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Mean percentage change in shortening fraction from baseline to the end of Induction I will be determined for eligible patients enrolled on Arms A, B and C.
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Timepoint [13]
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Up to 4 weeks
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Secondary outcome [14]
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Change in Ejection Fraction
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Assessment method [14]
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The mean percentage change in ejection fraction from baseline to the end of Induction I will be determined for eligible patients enrolled on Arms A, B and C.
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Timepoint [14]
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Up to 4 weeks
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Secondary outcome [15]
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Serum Concentrations of GVHD Biomarker
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Assessment method [15]
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The mean serum concentration of the day 28 GVHD biomarker will be estimated as well as the corresponding 95% confidence interval.
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Timepoint [15]
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Up to day 28 after SCT
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Eligibility
Key inclusion criteria
- Patients must be newly diagnosed with de novo acute myelogenous leukemia
- Patients with previously untreated primary AML who meet the customary criteria for AML
with >= 20% bone marrow blasts as set out in the 2008 World Health Organization (WHO)
Myeloid Neoplasm Classification are eligible
- Attempts to obtain bone marrow either by aspirate or biopsy must be made unless
clinically prohibitive; in cases where it is clinically prohibitive, peripheral
blood with an excess of 20% blasts and in which adequate flow cytometric and
cytogenetics/fluorescent in situ hybridization (FISH) testing is feasible can be
substituted for the marrow exam at diagnosis
- Patients with < 20% bone marrow blasts are eligible if they have:
- A karyotypic abnormality characteristic of de novo AML (t(8;21)(q22;q22),
inv(16)(p13q22) or t(16;16)(p13;q22) or 11q23 abnormalities
- The unequivocal presence of megakaryoblasts, or
- Biopsy proven isolated myeloid sarcoma (myeloblastoma; chloroma, including
leukemia cutis)
- Patients with any performance status are eligible for enrollment
- Prior therapy with hydroxyurea, all-trans retinoic acid (ATRA), corticosteroids (any
route), and IT cytarabine given at diagnosis is allowed; hydroxyurea and ATRA must be
discontinued prior to initiation of protocol therapy; patients who have previously
received any other chemotherapy, radiation therapy or any other antileukemic therapy
are not eligible for this protocol
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Minimum age
No limit
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Maximum age
29
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
- Patients with any of the following constitutional conditions are not eligible:
- Fanconi anemia
- Shwachman syndrome
- Any other known bone marrow failure syndrome
- Patients with constitutional trisomy 21 or with constitutional mosaicism of
trisomy 21 Note: enrollment may occur pending results of clinically indicated
studies to exclude these conditions
- Patients with any of the following oncologic diagnoses are not eligible:
- Any concurrent malignancy
- Juvenile myelomonocytic leukemia (JMML)
- Philadelphia chromosome positive AML
- Biphenotypic or bilineal acute leukemia
- Acute promyelocytic leukemia
- Acute myeloid leukemia arising from myelodysplasia
- Therapy-related myeloid neoplasms Note: enrollment may occur pending results of
clinically indicated studies to exclude these conditions
- Pregnancy and breast feeding
- Female patients who are pregnant are ineligible
- Lactating females are not eligible unless they have agreed not to breastfeed their
infants
- Female patients of childbearing potential are not eligible unless a negative pregnancy
test result has been obtained
- Sexually active patients of reproductive potential are not eligible unless they have
agreed to use an effective contraceptive method for the duration of their study
participation
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Active, not recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
20/06/2011
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
30/09/2027
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Actual
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Sample size
Target
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Accrual to date
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Final
1645
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
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Recruitment hospital [1]
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John Hunter Children's Hospital - Hunter Regional Mail Centre
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Recruitment hospital [2]
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Sydney Children's Hospital - Randwick
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Recruitment hospital [3]
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The Children's Hospital at Westmead - Westmead
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Recruitment hospital [4]
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Royal Brisbane and Women's Hospital - Herston
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Recruitment hospital [5]
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Royal Children's Hospital-Brisbane - Herston
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Recruitment hospital [6]
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Queensland Children's Hospital - South Brisbane
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Recruitment hospital [7]
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Royal Children's Hospital - Parkville
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Recruitment hospital [8]
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Princess Margaret Hospital for Children - Perth
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Recruitment postcode(s) [1]
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2310 - Hunter Regional Mail Centre
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Recruitment postcode(s) [2]
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2031 - Randwick
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Recruitment postcode(s) [3]
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2145 - Westmead
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Recruitment postcode(s) [4]
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4029 - Herston
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Recruitment postcode(s) [5]
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4101 - South Brisbane
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Recruitment postcode(s) [6]
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3052 - Parkville
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Recruitment postcode(s) [7]
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6008 - Perth
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Recruitment outside Australia
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United States of America
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State/province [1]
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Alabama
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Arizona
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Arkansas
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California
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Colorado
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Connecticut
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Delaware
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District of Columbia
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Florida
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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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South Carolina
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South Dakota
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Tennessee
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Texas
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Utah
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Vermont
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West Virginia
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Wisconsin
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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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Newfoundland and Labrador
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0
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Canada
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Nova Scotia
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0
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Canada
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Ontario
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Canada
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Quebec
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New Zealand
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Auckland
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New Zealand
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Christchurch
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Country [57]
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Puerto Rico
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State/province [57]
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San Juan
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Funding & Sponsors
Primary sponsor type
Government body
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Name
National Cancer Institute (NCI)
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Address
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Ethics approval
Ethics application status
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Summary
Brief summary
This randomized phase III trial studies how well bortezomib and sorafenib tosylate work in
treating patients with newly diagnosed acute myeloid leukemia. Bortezomib and sorafenib
tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell
growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells,
either by killing the cells or by stopping them from dividing. Giving bortezomib and
sorafenib tosylate together with combination chemotherapy may be an effective treatment for
acute myeloid leukemia.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT01371981
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Richard Aplenc
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Address
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Children's Oncology Group
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01371981
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