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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02883049




Registration number
NCT02883049
Ethics application status
Date submitted
22/08/2016
Date registered
30/08/2016
Date last updated
21/08/2024

Titles & IDs
Public title
Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations
Scientific title
A Phase III Randomized Trial for Newly Diagnosed High Risk B-Lymphoblastic Leukemia (B-ALL) Including a Stratum Evaluating Dasatinib (NSC#732517) in Patients With Ph-like Tyrosine Kinase Inhibitor (TKI) Sensitive Mutations
Secondary ID [1] 0 0
NCI-2011-03797
Secondary ID [2] 0 0
NCI-2011-03797
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B Acute Lymphoblastic Leukemia 0 0
B Acute Lymphoblastic Leukemia, BCR-ABL1-Like 0 0
Central Nervous System Leukemia 0 0
Testicular 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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Clofarabine
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Cytarabine
Treatment: Drugs - Dasatinib
Treatment: Drugs - Daunorubicin Hydrochloride
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Doxorubicin Hydrochloride
Treatment: Drugs - Etoposide
Treatment: Drugs - Hydrocortisone Sodium Succinate
Other interventions - Laboratory Biomarker Analysis
Treatment: Drugs - Leucovorin Calcium
Treatment: Drugs - Mercaptopurine
Treatment: Drugs - Methotrexate
Treatment: Drugs - Pegaspargase
Treatment: Drugs - Prednisone
Treatment: Other - Radiation Therapy
Treatment: Drugs - Thioguanine
Treatment: Drugs - Vincristine Sulfate

Experimental: DS HR B-ALL (RER) - Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.

See outline for details.

Experimental: DS HR B-ALL (SER) - Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.

See outline for details.

Experimental: Group I Arm A (HR B-ALL) - Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.

See outline for details.

Experimental: Group I Arm B (HR B-ALL) (CLOSED 03/19/2018) - Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.

See outline for details.

Active comparator: Group II Arm A (VHR B-ALL - Control Arm) - Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.

See outline for details.

Experimental: Group II Arm B (VHR B-ALL - Exp Arm1) (CLOSED 02/15/2017) - Patients receive consolidation, interim maintenance, delayed intensification and maintenance therapies.

See outline for details.

Experimental: Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014) - Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.

See outline for details.

Experimental: Group III PH-like predicted TKI-sensitive kinase mutation - Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.

See outline for details.


Treatment: Drugs: Clofarabine
Given IV

Treatment: Drugs: Cyclophosphamide
Given IV

Treatment: Drugs: Cytarabine
Given IT, IV, or SC

Treatment: Drugs: Dasatinib
Given PO

Treatment: Drugs: Daunorubicin Hydrochloride
Given IV

Treatment: Drugs: Dexamethasone
PO or IV

Treatment: Drugs: Doxorubicin Hydrochloride
Given IV

Treatment: Drugs: Etoposide
Given IV

Treatment: Drugs: Hydrocortisone Sodium Succinate
Given IT

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Treatment: Drugs: Leucovorin Calcium
Given PO or IV

Treatment: Drugs: Mercaptopurine
Given PO

Treatment: Drugs: Methotrexate
Given IT and IV

Treatment: Drugs: Pegaspargase
Given IV

Treatment: Drugs: Prednisone
Given PO or IV

Treatment: Other: Radiation Therapy
Undergo radiation therapy

Treatment: Drugs: Thioguanine
Given PO

Treatment: Drugs: Vincristine Sulfate
Given IV
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Intervention code [3] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
DFS of Non-DS HR Post-induction Patients Receiving Intrathecal (IT) Methotrexate (MTX) Compared With Patients Receiving Intrathecal Triple Therapy (ITT) on a Modified Berlin-Frankfurt-Munster (MBFM) Interim Maintenance High-dose Methotrexate Backbone
Timepoint [1] 0 0
At 5 years
Primary outcome [2] 0 0
DFS of Non-DS VHR Post-Induction Patients Who Receive a Modified MBFM-IMHDM Regimen That Contains a Second IM (Control Arm) Compared to Patients Receive the Cyclophosphamide + Etoposide Containing Regimen (Experimental Arm 1)
Timepoint [2] 0 0
At 4 years
Secondary outcome [1] 0 0
Toxicity and Tolerability of Post-induction Age-adjusted ITT Compared to Age-adjusted IT MTX in Children With HR B-ALL
Timepoint [1] 0 0
Up to 10 years
Secondary outcome [2] 0 0
Toxicity and Tolerability of Experimental Arm 1 and Control Arm in Patients With VHR B-ALL
Timepoint [2] 0 0
Up to 10 years
Secondary outcome [3] 0 0
Induction Mortality in Patients With DS and HR B-ALL Treated With Modified Induction
Timepoint [3] 0 0
At 1 month
Secondary outcome [4] 0 0
5-year DFS in Patients With Down Syndrome (DS) and HR B-ALL Treated With Modified Induction and Post-Induction Therapy Regimen With MBFM-IMIDM
Timepoint [4] 0 0
At 5 years
Secondary outcome [5] 0 0
DFS for Children and Young Adults With Ph-like B-ALL and a Predicted Tyrosine Kinase Inhibitor (TKI)-Sensitive Mutation Treated With Dasatinib Plus MBFM-IMHDM
Timepoint [5] 0 0
Up to 4 years
Secondary outcome [6] 0 0
Toxicity and Tolerability of MBFM-interim Maintenance Intermediate Dose Methotrexate (IMIDM) in Children With Down Syndrome
Timepoint [6] 0 0
Up to 10 years
Secondary outcome [7] 0 0
Overall Survival (OS) Rate for HR B-ALL Patients, Overall and by Randomized Arm
Timepoint [7] 0 0
At 5 years
Secondary outcome [8] 0 0
Overall Survival (OS) Rate for VHR B-ALL Patients, Overall and by Randomized Arm.
Timepoint [8] 0 0
At 4 years
Secondary outcome [9] 0 0
Incidence of Osteonecrosis (ON) Defined by Magnetic Resonance (MR) Imaging in Children, Adolescents, and Young Adults 10 Years of Age and Greater
Timepoint [9] 0 0
Up to 10 years
Secondary outcome [10] 0 0
The Prevalence of Cognitive Deficits Measured by CogState (Domain: Working Memory), in Children (Ages 6 to < 13 Years) With HR- and VHR B-ALL at 1 Year Off Therapy
Timepoint [10] 0 0
Up to 10 years
Secondary outcome [11] 0 0
The Prevalence of Cognitive Deficits Measured by CogState (Domain: Executive Function), in Children (Ages 6 to < 13 Years) With HR- and VHR B-ALL at 1 Year Off Therapy
Timepoint [11] 0 0
Up to 10 years
Secondary outcome [12] 0 0
The Prevalence of Cognitive Deficits Measured by CogState (Domain: Visual Learning), in Children (Ages 6 to < 13 Years) With HR- and VHR B-ALL at 1 Year Off Therapy
Timepoint [12] 0 0
Up to 10 years
Secondary outcome [13] 0 0
The Prevalence of Cognitive Deficits Measured by CogState (Domain: Processing Speed), in Children (Ages 6 to < 13 Years) With HR- and VHR B-ALL at 1 Year Off Therapy
Timepoint [13] 0 0
Up to 10 years
Secondary outcome [14] 0 0
The Prevalence of Cognitive Deficits Measured by CogState (Domain: Visual Attention), in Children (Ages 6 to < 13 Years) With HR- and VHR B-ALL at 1 Year Off Therapy
Timepoint [14] 0 0
Up to 10 years

Eligibility
Key inclusion criteria
* Patients must be enrolled on APEC14B1 and consented to Eligibility Screening on the Part A consent form prior to enrollment on AALL1131
* White Blood Cell Count (WBC) Criteria

* Age 1-9.99 years: WBC >= 50 000/uL
* Age 10-30.99 years: Any WBC
* Age 1-30.99 years: Any WBC with:

* Testicular leukemia
* CNS leukemia (CNS3)
* Steroid pretreatment
* Patients must have newly diagnosed B lymphoblastic leukemia (2008 World Health Organization [WHO] classification) (also termed B-precursor acute lymphoblastic leukemia); patients with Down syndrome are also eligible
* Organ function requirements for patients with Ph-like ALL and a predicted TKI-sensitive mutation: patients identified as Ph-like with a TKI-sensitive kinase mutation must have assessment of organ function performed within 3 days of study entry onto the dasatinib arm of AALL1131
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) > 70mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

* Age: Maximum Serum Creatinine (mg/dL)
* 1 to < 6 months: 0.4 (male) 0.4 (female)
* 6 months to < 1 year: 0.5 (male) 0.5 (female)
* 1 to < 2 years: 0.6 (male) 0.6 (female)
* 2 < 6 years: 0.8 (male) 0.8 (female)
* 6 to < 10 years: 1.0 (male) 1.0 (female)
* 10 to < 13 years: 1.2 (male) 1.2 (female)
* 13 to < 16 years: 1.5 (male) 1.4 (female)
* > 16 years: 1.7 (male) 1.4 (female)
* Direct bilirubin =< 3 x upper limit of normal (ULN) for age, and
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 10 x upper limit of normal (ULN) for age
* Shortening fraction >= 27% by echocardiogram, or ejection fraction >= 50% by gated radionuclide study

* Patients must have an electrocardiogram (EKG) fewer than 6 days prior to enrollment on the dasatinib arm; patients who have had cardiac assessments by echocardiogram or radionuclide scan at the beginning of induction do not need to have these repeated prior to study entry; correct QT interval (QTc) < 450 msec on baseline electrocardiogram as measured by the Friderica or Bazett formula
* No major conduction abnormality (unless a cardiac pacemaker is present)
* No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% at sea level if there is clinical indication for determination
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled; however, drugs that induce CYP3A4/5 (carbamazepine, oxcarbazepine, phenytoin, primidone, phenobarbital) should be avoided
* Eligibility criteria for the Longitudinal, Computerized Assessment of Neurocognitive Functioning study

* Patients must be aged 6 to 13 years at time of B-ALL diagnosis, enrolled on AALL1131
* Patients must be English-, French- or Spanish-speaking (languages in which the assessment is available)
* Patients must have no known history of neurodevelopmental disorder prior to diagnosis of B-ALL (e.g., Down syndrome, Fragile X, William's Syndrome, mental retardation)
* Patients must have no significant visual impairment that would prevent computer use and recognition of the visual test stimuli
* Eligibility criteria for the National Cancer Institute (NCI) standard risk patients from AALL0932 enrolling on this study at the end of Induction
* Effective March 19, 2018, patients enrolled on AALL0932, without Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 or the HR B-ALL stratum of this study at the end of Induction:

* Without favorable cytogenetics (no ETV6-RUNX1 or double trisomies 4+10), with day 8 peripheral blood (PB) minimal residual disease (MRD) >= 1% and day 29 bone marrow (BM) MRD < 0.01%
* With favorable cytogenetics (ETV6-RUNX1 or double trisomies 4+10), with any day 8 PB MRD and day 29 BM MRD >= 0.01%
* Both NCI standard risk (SR) and HR patients without Down syndrome and with testicular disease at diagnosis, who do not meet other VHR criteria
* Effective Amendment 6, patients enrolled on AALL0932, without Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 or the VHR stratum of AALL1131:

* Intrachromosomal amplification of chromosome 21 (iAMP21)
* Mixed-lineage leukemia (MLL) rearrangement
* Hypodiploidy (n < 44 chromosomes and/or a deoxyribonucleic acid [DNA] index < 0.81)
* Induction failure (M3 BM at day 29)
* Without favorable cytogenetics (no ETV6-RUNX1 or double trisomies 4+10), with day 29 BM MRD >= 0.01%
* Patients enrolled on AALL0932, with Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 but WILL BE eligible to enroll on the DS HR B-ALL stratum of this study at the end of Induction:

* Day 29 MRD >= 0.01%
* MLL rearrangement
* Hypodiploidy (n < 45 chromosomes and/or DNA index < 0.81)
* DS HR B-ALL patients initially enrolled on AALL0932 or this study who have Induction failure (M3 BM day 29) or Philadelphia chromosome (BCR-ABL1) will not be eligible for post-Induction therapy on either trial (AALL0932 or AALL1131)
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and NCI requirements for human studies must be met
Minimum age
1 Year
Maximum age
31 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* With the exception of steroid pretreatment or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for either the current diagnosis of B-ALL or any cancer diagnosed prior to the initiation of protocol therapy on AALL1131; patients cannot have secondary B-ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy; patients receiving prior steroid therapy may be eligible for AALL1131
* Patients with BCR-ABL1 fusion are not eligible for post-induction therapy on this study but may be eligible to enroll in a successor Children's Oncology Group (COG) Philadelphia positive (Ph+) ALL trial by day 15 Induction
* DS HR B-ALL patients with Induction failure or BCR-ABL1
* Female patients who are pregnant are ineligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs
* Lactating females are not eligible unless they have agreed not to breastfeed their infant
* 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
29/02/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
22/09/2024
Actual
Sample size
Target
Accrual to date
Final
5949
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
John Hunter Children's Hospital - Hunter Regional Mail Centre
Recruitment hospital [2] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [3] 0 0
Royal Children's Hospital-Brisbane - Herston
Recruitment hospital [4] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [5] 0 0
Women's and Children's Hospital-Adelaide - North Adelaide
Recruitment hospital [6] 0 0
Monash Medical Center-Clayton Campus - Clayton
Recruitment hospital [7] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [8] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment hospital [9] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
2310 - Hunter Regional Mail Centre
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
5006 - North Adelaide
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment postcode(s) [6] 0 0
3052 - Parkville
Recruitment postcode(s) [7] 0 0
6008 - Perth
Recruitment postcode(s) [8] 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
State/province [2] 0 0
Alaska
Country [3] 0 0
United States of America
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Delaware
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Tennessee
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Texas
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Vermont
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Lausanne

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Michael J Burke
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT02883049