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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01371981




Registration number
NCT01371981
Ethics application status
Date submitted
10/06/2011
Date registered
13/06/2011
Date last updated
5/08/2021

Titles & IDs
Public title
Bortezomib and Sorafenib Tosylate in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
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
Secondary ID [1] 0 0
NCI-2011-02670
Secondary ID [2] 0 0
NCI-2011-02670
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia 0 0
Leukemia Cutis 0 0
Myeloid Neoplasm 0 0
Myeloid Sarcoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue

Intervention/exposure
Study type
Interventional
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

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-free Survival (EFS) for Patients Without High Allelic Ratio FLT3/ITD+ Mutations - 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.
Timepoint [1] 0 0
Up to 3 years
Primary outcome [2] 0 0
EFS for Patients on Arm C, Cohort 1 - 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.
Timepoint [2] 0 0
Up to 3 years
Primary outcome [3] 0 0
EFS for Patients on Arm C, Cohort 2 - 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.
Timepoint [3] 0 0
Up to 3 years
Primary outcome [4] 0 0
EFS for Patients on Arm C, Cohort 3 - 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.
Timepoint [4] 0 0
Up to 3 years
Secondary outcome [1] 0 0
Overall Survival (OS) for Patients Without High Allelic Ratio FLT3/ITD+ Mutations - The Kaplan-Meier method will be used to estimate 3-year OS, defined as the time from study entry until death.
Timepoint [1] 0 0
Up to 3 years
Secondary outcome [2] 0 0
OS for Patients on Arm C, Cohort 1 - The Kaplan-Meier method will be used to estimate 3-year OS, defined as the time from study entry until death.
Timepoint [2] 0 0
Up to 3 years
Secondary outcome [3] 0 0
OS for Patients on Arm C, Cohort 2 - The Kaplan-Meier method will be used to estimate 3-year OS, defined as the time from study entry until death.
Timepoint [3] 0 0
Up to 3 years
Secondary outcome [4] 0 0
OS for Patients on Arm C, Cohort 3 - The Kaplan-Meier method will be used to estimate 3-year OS, defined as the time from study entry until death.
Timepoint [4] 0 0
Up to 3 years
Secondary outcome [5] 0 0
Relapse Rate for Patients Without High Allelic Ratio FLT3/ITD+ Mutations - 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.
Timepoint [5] 0 0
Up to 3 years
Secondary outcome [6] 0 0
Proportion of Patients Experiencing Grade 3 or Higher Non-hematologic Toxicities and Infections While on Protocol Therapy - 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).
Timepoint [6] 0 0
Up to 2 years
Secondary outcome [7] 0 0
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 - 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.
Timepoint [7] 0 0
Up to 8 weeks
Secondary outcome [8] 0 0
Total Scale Score From Parent-reported Pediatric Quality of Life Inventory Module - 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.
Timepoint [8] 0 0
Up to 14 days
Secondary outcome [9] 0 0
Total Scale Score From Parent-reported Cancer Module - 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.
Timepoint [9] 0 0
Up to 14 days
Secondary outcome [10] 0 0
Total Scale Score From Parent-reported Multidimensional Fatigue Scale Module - 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.
Timepoint [10] 0 0
Up to 14 days
Secondary outcome [11] 0 0
Bortezomib Clearance - Median and range of bortezomib clearance during Induction II.
Timepoint [11] 0 0
Day 8 of Induction II
Secondary outcome [12] 0 0
Sorafenib Steady State Concentration - Median and range of sorafenib steady state concentration for Induction I.
Timepoint [12] 0 0
Up to 30 days
Secondary outcome [13] 0 0
Change in Shortening Fraction - 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.
Timepoint [13] 0 0
Up to 4 weeks
Secondary outcome [14] 0 0
Change in Ejection Fraction - 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.
Timepoint [14] 0 0
Up to 4 weeks
Secondary outcome [15] 0 0
Serum Concentrations of GVHD Biomarker - The mean serum concentration of the day 28 GVHD biomarker will be estimated as well as the corresponding 95% confidence interval.
Timepoint [15] 0 0
Up to day 28 after SCT

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
Minimum age
No limit
Maximum age
29 Years
Gender
Both males and females
Can healthy volunteers participate?
No
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

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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
John Hunter Children's Hospital - Hunter Regional Mail Centre
Recruitment hospital [2] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [3] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [4] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [5] 0 0
Royal Children's Hospital-Brisbane - Herston
Recruitment hospital [6] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [7] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [8] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
2310 - Hunter Regional Mail Centre
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
4029 - Herston
Recruitment postcode(s) [5] 0 0
4101 - South Brisbane
Recruitment postcode(s) [6] 0 0
3052 - Parkville
Recruitment postcode(s) [7] 0 0
6008 - Perth
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
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Connecticut
Country [7] 0 0
United States of America
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Delaware
Country [8] 0 0
United States of America
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District of Columbia
Country [9] 0 0
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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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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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Texas
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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
State/province [48] 0 0
Alberta
Country [49] 0 0
Canada
State/province [49] 0 0
British Columbia
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Canada
State/province [50] 0 0
Manitoba
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Canada
State/province [51] 0 0
Newfoundland and Labrador
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Canada
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Nova Scotia
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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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Puerto Rico
State/province [57] 0 0
San Juan

Funding & Sponsors
Primary sponsor type
Government body
Name
National Cancer Institute (NCI)
Address
Country

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/show/NCT01371981
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Richard Aplenc
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

Summary results
Other publications