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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02828358




Registration number
NCT02828358
Ethics application status
Date submitted
7/07/2016
Date registered
11/07/2016
Date last updated
15/07/2019

Titles & IDs
Public title
Azacitidine and Combination Chemotherapy in Treating Infants With Acute Lymphoblastic Leukemia and KMT2A Gene Rearrangement
Scientific title
A Groupwide Pilot Study to Test the Tolerability and Biologic Activity of the Addition of Azacitidine (NSC# 102816) to Chemotherapy in Infants With Acute Lymphoblastic Leukemia (ALL) and KMT2A(MLL) Gene Rearrangement
Secondary ID [1] 0 0
NCI-2016-00973
Secondary ID [2] 0 0
NCI-2016-00973
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Leukemia of Ambiguous Lineage 0 0
B Acute Lymphoblastic Leukemia 0 0
KMT2A Gene Rearrangement 0 0
Mixed Phenotype Acute Leukemia 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
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Azacitidine
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Cytarabine
Treatment: Drugs - Daunorubicin Hydrochloride
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Hydrocortisone Sodium Succinate
Other interventions - Laboratory Biomarker Analysis
Treatment: Drugs - Leucovorin Calcium
Treatment: Drugs - Mercaptopurine
Treatment: Drugs - Methotrexate
Treatment: Drugs - Pegaspargase
Other interventions - Pharmacological Study
Treatment: Drugs - Prednisolone
Treatment: Drugs - Thioguanine
Treatment: Drugs - Vincristine Sulfate

Experimental: Treatment (azacitidine, combination chemotherapy) - See Detailed Description


Treatment: Drugs: Azacitidine
Given IV

Treatment: Drugs: Cyclophosphamide
Given IV

Treatment: Drugs: Cytarabine
Given IV, SC, IT

Treatment: Drugs: Daunorubicin Hydrochloride
Given IV

Treatment: Drugs: Dexamethasone
Given PO, NG, IV

Treatment: Drugs: Hydrocortisone Sodium Succinate
Given IT

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Treatment: Drugs: Leucovorin Calcium
Given PO, IV

Treatment: Drugs: Mercaptopurine
Given PO, NG

Treatment: Drugs: Methotrexate
Given IT, IV, PO

Treatment: Drugs: Pegaspargase
Given IV

Other interventions: Pharmacological Study
Correlative studies

Treatment: Drugs: Prednisolone
Given PO, NG

Treatment: Drugs: Thioguanine
Given PO, NG

Treatment: Drugs: Vincristine Sulfate
Given IV

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
Incidence of adverse events of azacitidine and combination chemotherapy - Will be graded according to Common Terminology Criteria for Adverse Events 4.0 (version 5.0 beginning April 1, 2018).
Timepoint [1] 0 0
From the first course of azacitidine administration up to fourth course of azacitidine administration
Secondary outcome [1] 0 0
Biologic activity, defined as global deoxyribonucleic acid (DNA) methylation change in peripheral blood mononuclear cells (PBMC)s - Will calculate the mean long interspersed nucleotide element-1 (LINE-1) methylation for all patients before and after azacitidine and perform paired t-test analysis to determine if there is significant demethylation in the study population for the tested dose level.
Timepoint [1] 0 0
Prior to first course of azacitidine up to day 5 of second course of azacitidine

Eligibility
Key inclusion criteria
- Infants must be > 36 weeks gestational age at the time of enrollment

- Patients must have newly diagnosed B lymphoblastic leukemia (2008 World Health
Organization [WHO] classification) (also termed B-precursor acute lymphoblastic
leukemia) or acute leukemia of ambiguous lineage (ALUL), which includes mixed
phenotype acute leukemia (MPAL); for patients with ALUL, the morphology and
immunophenotype must be at least 50% B lymphoblastic

- Central nervous system (CNS) status must be determined based on a sample obtained
prior to the administration of any systemic or intrathecal chemotherapy, with the
exception of steroid pretreatment
Minimum age
No limit
Maximum age
364 Days
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients with known absence of KMT2A-rearrangement leukemia prior to enrollment

- Patients with Down syndrome

- Patients with secondary B acute lymphoblastic leukemia (B-ALL) that developed after
treatment of a prior malignancy with cytotoxic chemotherapy

- With the exception of steroid pretreatment or the administration of intrathecal
methotrexate or intrathecal cytarabine, receipt of any other prior cytotoxic
chemotherapy for either the current diagnosis of B-ALL or any cancer diagnosed prior
to the initiation of protocol therapy on AALL15P1

Study design
Purpose of the study
Treatment
Allocation to intervention
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
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
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)
WA
Recruitment hospital [1] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment hospital [2] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
6008 - Perth
Recruitment postcode(s) [2] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
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Alaska
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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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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 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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Washington
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West Virginia
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Wisconsin
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Manitoba
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Nova Scotia
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Ontario
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Canada
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Quebec
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Puerto Rico
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Caguas
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Puerto Rico
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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 pilot phase II trial studies the side effects of azacitidine and combination
chemotherapy in infants with acute lymphoblastic leukemia and KMT2A gene rearrangement. Drugs
used in chemotherapy, such as methotrexate, prednisolone, daunorubicin hydrochloride,
cytarabine, dexamethasone, vincristine sulfate, pegaspargase, hydrocortisone sodium
succinate, azacitidine, cyclophosphamide, mercaptopurine, leucovorin calcium, and thioguanine
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. Giving more than one drug
may kill more cancer cells.
Trial website
https://clinicaltrials.gov/show/NCT02828358
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Erin M Guest
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
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02828358