International Phase 3 Trial in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL) Testing Imatinib in Combination with Two Different Cytotoxic Chemotherapy Backbones.

Inclusion Criteria

- For patients enrolled on APEC14B1 prior to enrollment on AALL1631, the required

diagnostic bone marrow sample has been fulfilled

- For patients who have not previously enrolled on APEC14B1 prior to enrollment on

AALL1631, a baseline diagnostic sample (or peripheral blood sample with blasts if

marrow sample unavailable) must be available to develop an MRD probe

- In addition, laboratory reports detailing evidence of BCR-ABL1 fusion or

ABL-class fusion must be submitted for rapid central review within 72 hours of

study enrollment

- >= 1 year (365 days) and =< 21 years at ALL diagnosis

- Ph+ (BCR-ABL1 fusion): newly diagnosed de novo ALL (B-ALL or T-ALL) or mixed

phenotypic acute leukemia (MPAL meeting 2016 World Health Organization [WHO]

definition) with definitive evidence of BCR-ABL1 fusion by karyotype, fluorescence in

situ hybridization (FISH) and/or molecular methodologies

- ABL-class fusion: newly diagnosed B-ALL with definitive evidence of ABL-class fusions.

ABL-class fusions are defined as those involving the following genes: ABL1, ABL2,

CSF1R, PDGFRB, PDGFRA. Methods of detection include fluorescence in-situ hybridization

(FISH, e.g. using break-apart or colocalization signals probes), multiplex or

singleplex reverse-transcription polymerase chain reaction (RT-PCR), whole

transcriptome or panel-based ribonucleic acid (RNA)-sequencing (e.g. TruSight RNA

Pan-Cancer Panel; Illumina, San Diego, CA, USA or similar)

- Ph+ patients must have previously started Induction therapy, which includes

vincristine, a corticosteroid, pegaspargase, with or without anthracycline, and/or

other standard cytotoxic chemotherapy

- Ph+ patients have not received more than 14 days of multiagent Induction therapy

beginning with the first dose of vinCRIStine

- Ph+ patients may have started imatinib prior to study entry but have not received more

than 14 days of imatinib

- ABL-class fusion patients must have previously completed the 4 or 5 weeks of

multiagent Induction chemotherapy (Induction IA phase)

- ABL-class fusion patients may have started imatinib during Induction IA, at the same

time of or after the first vinCRIStine dose

- Patients must have a performance status corresponding to Eastern Cooperative Oncology

Group (ECOG) scores of 0, 1, or 2

- Direct bilirubin =< 2.0 mg/dL

- Shortening fraction of >= 27% by echocardiogram

- Ejection fraction of >= 50% by radionuclide angiogram or echocardiogram

- Corrected QT interval, QTc < 480 msec

- Note: Repeat echocardiogram and electrocardiogram are not required if they were

performed at or after initial ALL diagnosis, before study enrollment

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70

mL/min/1.73 m^2 or serum creatinine within normal limits based on age/gender, as

follows:

- 1 to < 2 years: maximum serum creatinine 0.6 mg/dL (both male and female)

- 2 to < 6 years: maximum serum creatinine 0.8 mg/dL (both male and female)

- 6 to < 10 years: maximum serum creatinine 1 mg/dL (both male and female)

- 10 to < 13 years: maximum serum creatinine 1.2 mg/dL (both male and female)

- 13 to < 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female)

- >= 16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female)

Exclusion Criteria

- Known history of chronic myelogenous leukemia (CML)

- ALL developing after a previous cancer treated with cytotoxic chemotherapy

- Active, uncontrolled infection, or active systemic illness that requires ongoing

vasopressor support or mechanical ventilation

- Down syndrome

- Pregnancy and breast feeding

- 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 treatment according to

protocol

- Patients with congenital long QT syndrome, history of ventricular arrhythmias or heart

block

- Prior treatment with dasatinib, or any TKI other than imatinib