NCT02883049 · CITED IN SOURCE DOCUMENTS

Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2026-06-02

This randomized phase III trial studies how well combination chemotherapy works in treating young patients with newly diagnosed B acute lymphoblastic leukemia that is likely to come back or spread, and in patients with Philadelphia chromosome (Ph)-like tyrosine kinase inhibitor (TKI) sensitive mutations. Chemotherapy drugs, 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 (combination chemotherapy) and giving the drugs in different doses and in different combinations may kill more cancer cells.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

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

→

outcome · POSTED

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)

→

outcome · POSTED

Toxicity and Tolerability of Post-induction Age-adjusted ITT Compared to Age-adjusted IT MTX in Children With HR B-ALL

→

outcome · POSTED

Toxicity and Tolerability of Experimental Arm 1 and Control Arm in Patients With VHR B-ALL

→

outcome · POSTED

Induction Mortality in Patients With DS and HR B-ALL Treated With Modified Induction

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · POSTED

Toxicity and Tolerability of MBFM-interim Maintenance Intermediate Dose Methotrexate (IMIDM) in Children With Down Syndrome

→

outcome · POSTED

Overall Survival (OS) Rate for HR B-ALL Patients, Overall and by Randomized Arm

→

outcome · POSTED

Overall Survival (OS) Rate for VHR B-ALL Patients, Overall and by Randomized Arm.

→

outcome · POSTED

Incidence of Osteonecrosis (ON) Defined by Magnetic Resonance (MR) Imaging in Children, Adolescents, and Young Adults 10 Years of Age and Greater

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · NOT POSTED

The Reduction in MRD From End-Induction (EOI) to End-Consolidation (EOC) for Children, Adolescents, and Young Adults With VHR B-ALL Receiving Experimental Arms 1 Compared to the Control Arm

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

eligibility Criteria: 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 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
healthy Volunteers: false
maximum Age: 31 Years
minimum Age: 1 Year
sex: ALL
std Ages: CHILD
ADULT

Treatment arms and interventions

arm Groups

description
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies. See outline for details.
intervention Names
Drug: Cyclophosphamide
Drug: Cytarabine
Drug: Dexamethasone
Drug: Doxorubicin Hydrochloride
Other: Laboratory Biomarker Analysis
Drug: Leucovorin Calcium
Drug: Mercaptopurine
Drug: Methotrexate
Drug: Pegaspargase
Drug: Prednisone
Radiation: Radiation Therapy
Drug: Thioguanine
label
DS HR B-ALL (RER)
type
EXPERIMENTAL
description
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies. See outline for details.
intervention Names
Drug: Cyclophosphamide
Drug: Cytarabine
Drug: Daunorubicin Hydrochloride
Drug: Dexamethasone
Drug: Doxorubicin Hydrochloride
Other: Laboratory Biomarker Analysis
Drug: Leucovorin Calcium
Drug: Mercaptopurine
Drug: Methotrexate
Drug: Pegaspargase
Drug: Prednisone
Radiation: Radiation Therapy
label
DS HR B-ALL (SER)
type
EXPERIMENTAL
description
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies. See outline for details.
intervention Names
Drug: Cyclophosphamide
Drug: Cytarabine
Drug: Daunorubicin Hydrochloride
Drug: Dexamethasone
Drug: Doxorubicin Hydrochloride
Other: Laboratory Biomarker Analysis
Drug: Leucovorin Calcium
Drug: Mercaptopurine
Drug: Methotrexate
Drug: Pegaspargase
Drug: Prednisone
Radiation: Radiation Therapy
label
Group I Arm A (HR B-ALL)
type
EXPERIMENTAL
description
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies. See outline for details.
intervention Names
Drug: Cyclophosphamide
Drug: Cytarabine
Drug: Daunorubicin Hydrochloride
Drug: Dexamethasone
Drug: Doxorubicin Hydrochloride
Drug: Hydrocortisone Sodium Succinate
Other: Laboratory Biomarker Analysis
Drug: Leucovorin Calcium
Drug: Mercaptopurine
Drug: Methotrexate
Drug: Pegaspargase
Drug: Prednisone
label
Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)
type
EXPERIMENTAL
description
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies. See outline for details.
intervention Names
Drug: Cyclophosphamide
Drug: Cytarabine
Drug: Daunorubicin Hydrochloride
Drug: Dexamethasone
Drug: Doxorubicin Hydrochloride
Other: Laboratory Biomarker Analysis
Drug: Leucovorin Calcium
Drug: Mercaptopurine
Drug: Methotrexate
Drug: Pegaspargase
Drug: Prednisone
Radiation: Radiation Therapy
label
Group II Arm A (VHR B-ALL - Control Arm)
type
ACTIVE_COMPARATOR
description
Patients receive consolidation, interim maintenance, delayed intensification and maintenance therapies. See outline for details.
intervention Names
Drug: Cyclophosphamide
Drug: Cytarabine
Drug: Daunorubicin Hydrochloride
Drug: Doxorubicin Hydrochloride
Drug: Etoposide
Other: Laboratory Biomarker Analysis
Drug: Leucovorin Calcium
Drug: Mercaptopurine
Drug: Methotrexate
Drug: Pegaspargase
Drug: Prednisone
Radiation: Radiation Therapy
label
Group II Arm B (VHR B-ALL - Exp Arm1) (CLOSED 02/15/2017)
type
EXPERIMENTAL
description
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies. See outline for details.
intervention Names
Drug: Clofarabine
Drug: Cyclophosphamide
Drug: Cytarabine
Drug: Daunorubicin Hydrochloride
Drug: Dexamethasone
Drug: Doxorubicin Hydrochloride
Drug: Etoposide
Other: Laboratory Biomarker Analysis
Drug: Leucovorin Calcium
Drug: Mercaptopurine
Drug: Methotrexate
Drug: Pegaspargase
label
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
type
EXPERIMENTAL
description
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies. See outline for details.
intervention Names
Drug: Cyclophosphamide
Drug: Cytarabine
Drug: Dasatinib
Drug: Daunorubicin Hydrochloride
Drug: Dexamethasone
Drug: Doxorubicin Hydrochloride
Other: Laboratory Biomarker Analysis
Drug: Leucovorin Calcium
Drug: Mercaptopurine
Drug: Methotrexate
Drug: Pegaspargase
Drug: Prednisone
label
Group III PH-like predicted TKI-sensitive kinase mutation
type
EXPERIMENTAL

interventions

arm Group Labels
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
description
Given IV
name
Clofarabine
other Names
Clofarex
Clolar
type
DRUG
arm Group Labels
DS HR B-ALL (RER)
DS HR B-ALL (SER)
Group I Arm A (HR B-ALL)
Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)
Group II Arm A (VHR B-ALL - Control Arm)
Group II Arm B (VHR B-ALL - Exp Arm1) (CLOSED 02/15/2017)
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
Group III PH-like predicted TKI-sensitive kinase mutation
description
Given IV
name
Cyclophosphamide
other Names
(-)-Cyclophosphamide
2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
Asta B 518
B 518
B-518
B518
Carloxan
Ciclofosfamida
Ciclofosfamide
Cicloxal
Clafen
Claphene
type
DRUG
arm Group Labels
DS HR B-ALL (RER)
DS HR B-ALL (SER)
Group I Arm A (HR B-ALL)
Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)
Group II Arm A (VHR B-ALL - Control Arm)
Group II Arm B (VHR B-ALL - Exp Arm1) (CLOSED 02/15/2017)
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
Group III PH-like predicted TKI-sensitive kinase mutation
description
Given IT, IV, or SC
name
Cytarabine
other Names
.beta.-Cytosine arabinoside
1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
1-.beta.-D-Arabinofuranosylcytosine
1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
1-Beta-D-arabinofuranosylcytosine
1.beta.-D-Arabinofuranosylcytosine
2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
Alexan
Ara-C
ARA-cell
Arabine
type
DRUG
arm Group Labels
Group III PH-like predicted TKI-sensitive kinase mutation
description
Given PO
name
Dasatinib
other Names
BMS 354825
BMS-354825
BMS354825
Dasatinib Hydrate
Dasatinib Monohydrate
Sprycel
type
DRUG
arm Group Labels
DS HR B-ALL (SER)
Group I Arm A (HR B-ALL)
Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)
Group II Arm A (VHR B-ALL - Control Arm)
Group II Arm B (VHR B-ALL - Exp Arm1) (CLOSED 02/15/2017)
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
Group III PH-like predicted TKI-sensitive kinase mutation
description
Given IV
name
Daunorubicin Hydrochloride
other Names
Cerubidin
Cerubidine
Cloridrato de Daunorubicina
Daunoblastin
Daunoblastina
Daunoblastine
Daunomycin Hydrochloride
Daunomycin, hydrochloride
Daunorubicin.HCl
Daunorubicini Hydrochloridum
FI-6339
Ondena
type
DRUG
arm Group Labels
DS HR B-ALL (RER)
DS HR B-ALL (SER)
Group I Arm A (HR B-ALL)
Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)
Group II Arm A (VHR B-ALL - Control Arm)
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
Group III PH-like predicted TKI-sensitive kinase mutation
description
PO or IV
name
Dexamethasone
other Names
Aacidexam
Adexone
Aknichthol Dexa
Alba-Dex
Alin
Alin Depot
Alin Oftalmico
Amplidermis
Anemul mono
Auricularum
Auxiloson
Baycadron
type
DRUG
arm Group Labels
DS HR B-ALL (RER)
DS HR B-ALL (SER)
Group I Arm A (HR B-ALL)
Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)
Group II Arm A (VHR B-ALL - Control Arm)
Group II Arm B (VHR B-ALL - Exp Arm1) (CLOSED 02/15/2017)
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
Group III PH-like predicted TKI-sensitive kinase mutation
description
Given IV
name
Doxorubicin Hydrochloride
other Names
5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)
ADM
Adriacin
Adriamycin
Adriamycin Hydrochloride
Adriamycin PFS
Adriamycin RDF
ADRIAMYCIN, HYDROCHLORIDE
Adriamycine
Adriblastina
Adriblastine
Adrimedac
type
DRUG
arm Group Labels
Group II Arm B (VHR B-ALL - Exp Arm1) (CLOSED 02/15/2017)
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
description
Given IV
name
Etoposide
other Names
Demethyl Epipodophyllotoxin Ethylidine Glucoside
EPEG
Lastet
Toposar
Vepesid
VP 16
VP 16-213
VP 16213
VP-16
VP-16-213
VP-16213
VP16
type
DRUG
arm Group Labels
Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)
description
Given IT
name
Hydrocortisone Sodium Succinate
other Names
(11beta)-21-(3-Carboxy-1-oxopropyl)-11,17-dihydroxypregn-4-ene-3,20-dione, Monosodium Salt
A-Hydrocort
Buccalsone
Corlan
Cortisol Sodium Succinate
Cortop
Efcortelan
Emergent-EZ
Flebocortid
Hidroc Clora
Hycorace
Hydro-Adreson
type
DRUG
arm Group Labels
DS HR B-ALL (RER)
DS HR B-ALL (SER)
Group I Arm A (HR B-ALL)
Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)
Group II Arm A (VHR B-ALL - Control Arm)
Group II Arm B (VHR B-ALL - Exp Arm1) (CLOSED 02/15/2017)
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
Group III PH-like predicted TKI-sensitive kinase mutation
description
Correlative studies
name
Laboratory Biomarker Analysis
type
OTHER
arm Group Labels
DS HR B-ALL (RER)
DS HR B-ALL (SER)
Group I Arm A (HR B-ALL)
Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)
Group II Arm A (VHR B-ALL - Control Arm)
Group II Arm B (VHR B-ALL - Exp Arm1) (CLOSED 02/15/2017)
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
Group III PH-like predicted TKI-sensitive kinase mutation
description
Given PO or IV
name
Leucovorin Calcium
other Names
Adinepar
Calcifolin
Calcium (6S)-Folinate
Calcium Folinate
Calcium Leucovorin
Calfolex
Calinat
Cehafolin
Citofolin
Citrec
Citrovorum Factor
Cromatonbic Folinico
type
DRUG
arm Group Labels
DS HR B-ALL (RER)
DS HR B-ALL (SER)
Group I Arm A (HR B-ALL)
Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)
Group II Arm A (VHR B-ALL - Control Arm)
Group II Arm B (VHR B-ALL - Exp Arm1) (CLOSED 02/15/2017)
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
Group III PH-like predicted TKI-sensitive kinase mutation
description
Given PO
name
Mercaptopurine
other Names
3H-Purine-6-thiol
6 MP
6 Thiohypoxanthine
6 Thiopurine
6-Mercaptopurine
6-Mercaptopurine Monohydrate
6-MP
6-Purinethiol
6-Thiopurine
6-Thioxopurine
6H-Purine-6-thione, 1,7-dihydro- (9CI)
7-Mercapto-1,3,4,6-tetrazaindene
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 5949
type: ACTUAL

Registered outcome plans (not posted results)

other Outcomes

description
(Closed effective Amendment 6) Mean change in MRD from EOI to EOC will be calculated for VHR patients on Experimental Arm 1 and Control Arm.
measure
The Reduction in MRD From End-Induction (EOI) to End-Consolidation (EOC) for Children, Adolescents, and Young Adults With VHR B-ALL Receiving Experimental Arms 1 Compared to the Control Arm
time Frame
Up to 90 days

primary Outcomes

description
DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. Compared using 2-sided log rank test, alpha = 5%. (Completed effective March 19, 2018)
measure
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
time Frame
At 5 years
description
(Completed effective February 15, 2017) DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. Compared using a 1-sided log rank test, alpha of 2.5%.
measure
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)
time Frame
At 4 years

secondary Outcomes

description
(Completed effective March 19, 2018) Percentage of patients who experienced Grade 3 or higher Toxicity Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, will be estimated for each randomized arm.
measure
Toxicity and Tolerability of Post-induction Age-adjusted ITT Compared to Age-adjusted IT MTX in Children With HR B-ALL
time Frame
Up to 10 years
description
Percentage of patients who experienced Grade 3 or higher Toxicity Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, will be estimated for each randomized arm. (Closed effective February 15, 2017)
measure
Toxicity and Tolerability of Experimental Arm 1 and Control Arm in Patients With VHR B-ALL
time Frame
Up to 10 years
description
Percentage of deaths in induction will be calculated.
measure
Induction Mortality in Patients With DS and HR B-ALL Treated With Modified Induction
time Frame
At 1 month
description
DFS time is defined as time from end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. 5-year DFS will be estimated using the Kaplan-Meier method.
measure
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
time Frame
At 5 years
description
DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. 4-year DFS will be estimated using the Kaplan-Meier method.
measure
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
time Frame
Up to 4 years
description
Percentage of patients who experienced Grade 3 or higher Toxicity Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, will be estimated.
measure
Toxicity and Tolerability of MBFM-interim Maintenance Intermediate Dose Methotrexate (IMIDM) in Children With Down Syndrome
time Frame
Up to 10 years
description
OS time is defined as time from enrollment to death or date of last contact for patients who are alive. 5-year OS will be estimated for the two randomized arms using the Kaplan-Meier method.
measure
Overall Survival (OS) Rate for HR B-ALL Patients, Overall and by Randomized Arm
time Frame
At 5 years
description
OS of VHR-B-ALL 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). OS time is defined as time from enrollment to death or date of last contact for patients who are alive. 4-year OS will be estimated for the two randomized arms using the Kaplan-Meier method.
measure
Overall Survival (OS) Rate for VHR B-ALL Patients, Overall and by Randomized Arm.
time Frame
At 4 years
description
Incidence of ON among patients who have submitted MRI screening data will be estimated.
measure
Incidence of Osteonecrosis (ON) Defined by Magnetic Resonance (MR) Imaging in Children, Adolescents, and Young Adults 10 Years of Age and Greater
time Frame
Up to 10 years
description
The percentage of patients with abnormal results (Z ≤ -1.5) in working memory measured by CogState will be estimated.
measure
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
time Frame
Up to 10 years
description
The percentage of patients with abnormal results (Z ≤ -1.5) in executive function measured by CogState will be estimated.
measure
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
time Frame
Up to 10 years
description
The percentage of patients with abnormal results (Z ≤ -1.5) in visual learning measured by CogState will be estimated.
measure
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
time Frame
Up to 10 years

Full study description

brief Summary: This randomized phase III trial studies how well combination chemotherapy works in treating young patients with newly diagnosed B acute lymphoblastic leukemia that is likely to come back or spread, and in patients with Philadelphia chromosome (Ph)-like tyrosine kinase inhibitor (TKI) sensitive mutations. Chemotherapy drugs, 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 (combination chemotherapy) and giving the drugs in different doses and in different combinations may kill more cancer cells.
detailed Description: PRIMARY OBJECTIVES: I. To determine if the administration of post-Induction age-adjusted intrathecal triple therapy (ITT) on a Modified Berlin-Frankfurt-Munster (MBFM) interim maintenance high-dose methotrexate (IMHDM) backbone will improve 5-year disease-free survival (DFS) of children with high-risk (HR) B-acute lymphoblastic leukemia (ALL) compared to age-adjusted intrathecal (IT) methotrexate (MTX). (Completed effective March 19, 2018) II. To determine, in a randomized fashion, if the cyclophosphamide + etoposide containing regimen (Experimental Arm 1) will improve the 4-year DFS of children, adolescents, and young adults with very high-risk (VHR) B-ALL compared to a modified MBFM-IMHDM regimen that contains a second IM (Control Arm). (Completed effective February 15, 2017) SECONDARY OBJECTIVES: I. To determine the toxicity and tolerability of post-Induction age-adjusted ITT compared to age-adjusted IT MTX in children with HR B-ALL. (Completed effective March 19, 2018) II. To determine the toxicity and tolerability of Experimental Arm 1 compared to the Control Arm in children, adolescents, and young adults with VHR B-ALL. (Completed effective February 15, 2017) III. To determine whether a single-arm, modified Induction with limited anthracycline exposure and post-Induction therapy regimen with MBFM-interim maintenance intermediate dose methotrexate (IMIDM) and reduced vincristine (vincristine sulfate)/steroid pulse frequency and enhanced supportive care in children with Down syndrome (DS) and HR B-ALL will result in a \>= 65% 5-year DFS and \< 10% Induction mortality. IV. To describe the outcomes for children and young adults with Philadelphia chromosome (Ph)-like B-ALL and a predicted TKI-sensitive mutation treated with dasatinib plus MBFM-IMHDM. V. To determine the toxicity and tolerability of MBFM-IMIDM in children with DS and HR B-ALL. VI. To estimate overall survival (OS) rates both overall and by regimen a) for HR B-ALL and b) VHR B-ALL patients. VII. To determine the incidence of osteonecrosis (ON), defined by magnetic resonance (MR) imaging, and to characterize the natural history of clinically silent ON in children, adolescents, and young adults 10 years of age and greater and to assess the role of drugs (i.e., asparaginase and methotrexate) in addition to corticosteroids, in the risk for development of ON. (Completed accrual July 2016) VIII. To determine if the prevalence of cognitive deficits measured by CogState, in children (ages 6 to \< 13 years) with HR- and VHR B-ALL at 1 year off therapy, is significantly higher than the normative population (\> 14%) in the following domains: working memory, executive function, visual motor, processing speed, and visual attention. EXPLORATORY OBJECTIVE: I. To determine if the reduction of minimal residual disease (MRD) from end-Induction to end-Consolidation is greater for children, adolescents, and young adults with VHR B-ALL receiving Experimental Arm 1 compared to the Control Arm. (Closed effective October 20, 2017) OUTLINE: INDUCTION THERAPY: Patients without Down syndrome receive induction chemotherapy comprising cytarabine intrathecally (IT) on day 1 (and twice weekly thereafter for CNS2 patients \[except for days 8 and 29\]); vincristine sulfate intravenously (IV) over 1 minute on days 1, 8, 15, and 22; daunorubicin hydrochloride IV over 1-15 minutes on days 1, 8, 15, and 22; dexamethasone orally (PO) or IV twice daily (BID) on days 1-14 (patients under 10 years old) or prednisone PO or IV BID on days 1-28 (patients at least 10 years old); pegaspargase IV over 1-2 hours on day 4; and methotrexate IT on days 8 and 29 for CNS1 and CNS2 patients (plus days 15 and 22 for CNS3 patients). Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity. Participants are stratified to 1 of 3 disease groups: HR B-ALL, VHR B-ALL and PH-like B-ALL a predicted TKI-sensitive mutation. GROUP I - HR B-ALL: Patients are randomized to 1 of 2 treatment arms. (RANDOMIZATION CLOSED 03/19/2018) CONSOLIDATION THERAPY (C): ARM A HR B-ALL C: Patients receive consolidation therapy comprising cyclophosphamide IV over 30-60 minutes on days 1 and 29; cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO once daily (QD) on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15, and 22; vincristine sulfate IV over 1 minute on days 15, 22, 43, and 50; and pegaspargase IV over 1-2 hours on days 15 and 43. Patients with continuing clinical evidence of testicular leukemia undergo radiotherapy (RT) QD, 5 days a week, for approximately 2½ weeks (12 fractions total). Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity. ARM B HR B-ALL C: Patients receive consolidation therapy as in Arm I HR B-ALL C. Patients also receive ITT comprising methotrexate, hydrocortisone sodium succinate, and cytarabine on days 1, 8, 15, and 22. Patients with testicular leukemia also undergo RT as in Arm I HR B-ALL C. (CLOSED 03/19/2018) INTERIM MAINTENANCE THERAPY (IM) ARM A HR B-ALL IM: Patients receive IM therapy comprising vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43; high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46; methotrexate IT on days 1 and 29; and mercaptopurine PO on days 1-56. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity. ARM B HR B-ALL IM: Patients receive ITT on days 1 and 29 and IM therapy as in Arm I HR-ALL IM. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity. (CLOSED 03/19/2018) DELAYED INTENSIFICATION THERAPY (DI): ARM A HR B-ALL DI: Patients receive DI therapy comprising vincristine sulfate IV over 1 minute on days 1, 8, 15, 43, and 50; dexamethasone PO or IV BID on days 1-7 and 15-21; doxorubicin hydrochloride IV over 1-15 minutes on days 1, 8, and 15; methotrexate IT on days 1, 29, and 36; pegaspargase IV over 1-2 hours on days 4 and 43; cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; and thioguanine PO QD on days 29-42. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity. ARM B HR B-ALL DI: Patients receive ITT on days 1, 29, and 36 and DI therapy as in Arm I HR B-ALL DI. (CLOSED 03/19/2018) MAINTENANCE THERAPY (M): ARM A HR B-ALL M: Patients receive maintenance therapy comprising vincristine sulfate IV over 1 minute on days 1, 29, and 57; methotrexate IT on day 1 (also day 29 of courses 1-4); prednisone PO BID on days 1-5, 29-33 (may receive methylprednisolone IV if PO is not tolerated), and 57-61; mercaptopurine PO QD on days 1-84; and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicity. ARM B HR B-ALL M: Patients receive ITT on day 1 (also day 29 of courses 1-4) and maintenance therapy as in Arm I HR B-ALL M. Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicity. (CLOSED 03/19/2018) GROUP II: VHR B-ALL: Patients are randomized to 1 of 3 treatment arms. (RANDOMIZATION CLOSED 02/15/2017) CONSOLIDATION THERAPY PART I: In all arms, patients receive cyclophosphamide IV over 30-60 minutes on day 1; cytarabine IV over 1-30 minutes or SC on days 1-4 and 8-11; mercaptopurine PO QD on days 1-14; methotrexate IT on days 1, 8, 15, and 22 (days 1 and 8 only for CNS3 patients); vincristine sulfate IV over 1 minute on days 15 and 22; and pegaspargase IV over 1-2 hours on day 15. Patients with continuing clinical evidence of testicular leukemia undergo RT QD, 5 days a week, for approximately 2½ weeks (12 fractions total). Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. CONSOLIDATION THERAPY PART II: ARM A VHR B-ALL C (CONTROL ARM): Patients receive consolidation therapy comprising cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; mercaptopurine PO QD on days 29-42; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. ARM B VHR B-ALL C (EXPERIMENTAL ARM 1): Patients receive consolidation therapy comprising cyclophosphamide IV over 15-30 minutes on days 29-33; etoposide IV over 60-120 minutes on days 29-33; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. (CLOSED 02/15/2017) ARM C VHR B-ALL C (EXPERIMENTAL ARM 2): Patients receive clofarabine IV over 2 hours on days 29-33 and consolidation therapy as in Arm B VHR B-ALL C. (CLOSED 9/12/2014) INTERIM MAINTENANCE THERAPY PART I: In all arms, patients receive vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43; high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46; mercaptopurine PO QD on days 1-56; and methotrexate IT on days 1 and 29. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity. DELAYED INTENSIFICATION THERAPY PART I: In all arms, patients receive vincristine sulfate IV over 1 minute on days 1, 8, and 15; dexamethasone PO or IV BID on days 1-7 and 15-21; doxorubicin hydrochloride IV over 1-15 minutes on days 1, 8, and 15; methotrexate IT on day 1; and pegaspargase IV over 1-2 hours on day 4. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. DELAYED INTENSIFICATION THERAPY PART II: ARM A VHR B-ALL DI (CONTROL ARM): Patients receive DI therapy comprising cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; thioguanine PO QD on days 29-42; methotrexate IT on days 29 and 36; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. ARM B VHR B-ALL DI (EXPERIMENTAL ARM 1): Patients receive DI therapy comprising cyclophosphamide IV over 15-30 minutes on days 29-33; etoposide IV over 60-120 minutes on days 29-33; methotrexate IT on days 29 and 36; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. (CLOSED 02/15/2017) ARM C VHR B-ALL DI (EXPERIMENTAL ARM 2): Patients receive clofarabine IV over 2 hours on days 29-33 and DI therapy as in Arm II B VHR B-ALL DI. (Closed as of 9/12/2014) INTERIM MAINTENANCE THERAPY PART II: In all arms, patients receive vincristine sulfate IV over 1 minute and methotrexate IV over 2-5 minutes (undiluted) or 10-15 minutes (diluted) on days 1, 11, 21, 31, and 41; pegaspargase IV over 1-2 hours on days 2 and 22; and methotrexate IT on days 1 and 31. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity. MAINENTANCE THERAPY: Patients with CNS3 disease at diagnosis undergo RT QD over 4 weeks (10 fractions total). In all arms, patients receive vincristine sulfate IV over 1 minute on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61 (may receive methylprednisolone IV if PO is not tolerated); methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (except on methotrexate IT days); mercaptopurine PO QD on days 1-84; methotrexate IT on day 1 (also day 29 of courses 1 and 2 for CNS patients who did not undergo RT). Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicities. GROUP III: PH-LIKE PREDICTED TKI-SENSITIVE KINASE MUTATION: CONSOLIDATION THERAPY: Patients receive dasatinib PO QD on days 1-56, cyclophosphamide IV over 30-60 minutes on days 1 and 29, cytarabine IV over 1-30 minutes or SC on days 1-4, 8-11, 29-32 and 36-39, mercaptopurine PO on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15 and 22 (days 1 and 8 only for CNS3 patients), vincristine sulfate IV over 1 minute on days 15, 22, 43 and 50, and pegaspargase IV over 1-2 hours on days 15 and 43. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity. INTERIM MAINTENANCE THERAPY I: Patients receive dasatinib PO QD on days 1-63, vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43, high dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46, methotrexate IT on days 1 and 29, and mercaptopurine PO on days 1-56. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity. DELAYED INTENSIFICATION THERAPY: Patients receive dasatinib PO QD on days 1-56, vincristine sulfate IV over 1 minute on days 1, 8, 15, 43, and 50, dexamethasone PO or IV on days 1-7 and 15-21, doxorubicin hydrochloride IV over 1-15 minutes on days 1, 8 and 15, methotrexate IT on days 1, 29 and 36, pegaspargase IV over 1-2 hours on days 4 and 43, cyclophosphamide IV over 30-60 minutes day 29, cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39, and thioguanine PO on days 29-42. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity. INTERIM MAINTENANCE THERAPY II: Patients dasatinib PO QD on days 1-56, vincristine sulfate IV over 1 minute days 1, 11, 21, 31, and 41, methotrexate IV over 2-5 minutes (undiluted) or 10-15 minutes (diluted) on days 1, 11, 21, 31 and 41, methotrexate IT on days 1 and 31, and pegaspargase IV over 1-2 hours days 2 and 22. MAINTENANCE THERAPY: Patients receive dasatinib PO QD on days 1-84, vincristine sulfate IV over 1 minute on days 1, 29 and 57, prednisone PO BID or IV on days 1-5, 29-33 and 57-61, methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 78 (omit on days when MTX \[IT\] is given), mercaptopurine PO on days 1-84, methotrexate IT on day 1 (also day 29 of course 1 and 2, for patients who did not receive CNS radiation). Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicities. Participants with Down syndrome are assigned to DS HR B-ALL: INDUCTION THERAPY: All patients receive cytarabine IT on day 1; vincristine sulfate IV over 1 minute on days 1 and 8, dexamethasone PO or IV BID (patients under 10 years old) or prednisone PO BID (patients at least 10 years old) on days 1-14 (may receive methylprednisolone IV if PO is not tolerated), pegaspargase IV over 1-2 hours on day 4; methotrexate IT on day 8; and leucovorin calcium PO on days 10-11. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity. RAPID EARLY RESPONDERS (RER): Patients receive induction therapy comprising vincristine sulfate IV over 1 minute on days 15 and 22; dexamethasone PO BID (patients under 10 years old) or prednisone PO BID (patients at least 10 years old) on days 15-28; methotrexate IT on day 29 (also days 15 and 22 for CNS3 patients); and leucovorin calcium PO on days 31-32 (also days 17-18 and 24-25 for CNS3 patients). Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity. SLOW EARLY RESPONDERS (SER): Patients receive daunorubicin hydrochloride IV over 1-15 minutes on day 15 and Induction therapy as RER patients. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity. CONSOLIDATION THERAPY: All patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29; cytarabine IV over 1-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO QD on days 1-14 and 29-42; vincristine sulfate IV over 1 minute on days 15, 22, 43, and 50; pegaspargase IV over 1-2 hours on days 15 and 43; methotrexate IT on days 1, 8, 15, and 22 (days 1 and 8 only for CNS3 patients); and leucovorin calcium PO on days 3-4, 10-11, 17-18, and 24-25. Patients with continuing clinical evidence of testicular leukemia undergo RT QD, 5 days a week, for approximately 2½ weeks (12 fractions total). Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity. INTERIM MAINTENANCE THERAPY: Patients receive vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43; intermediate dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium PO or IV on days 2-3, 17-18, 31-32, and 45-46; mercaptopurine PO QD on days 1-56; and methotrexate IT on days 1 and 29. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity. DELAYED INTENSIFICATION THERAPY: Patients receive vincristine sulfate IV over 1 minute on days 1, 8, 15, 43, and 50; dexamethasone PO BID or IV on days 1-7 and 15-21; doxorubicin hydrochloride IV over 1-15 minutes on days 1, 8, and 15; pegaspargase IV over 1-2 hours on days 4 and 43; cyclophosphamide IV over 30-60 minutes on day 29; thioguanine PO QD on days 29-42; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; methotrexate IT on days 1, 29, and 36; and leucovorin calcium PO on days 3-4, 31-32 and 38-39. MAINTENANCE THERAPY: Patients with CNS3 disease undergo RT QD, 5 days a week, for 2 weeks (10 fractions total). Patients receive vincristine sulfate IV over 1 minute on day 1; prednisone PO BID or IV on days 1-5 (may receive methylprednisolone IV if PO not tolerated); methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO QD on days 1-84; and methotrexate IT on day 1 (also day 29 of courses 1-4 for CNS3 patients who did not undergo RT). Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicities. After completion of study treatment, patients are followed up periodically for 10 years.

Source references

references

citation
Chang TC, Chen W, Qu C, Cheng Z, Hedges D, Elsayed A, Pounds SB, Shago M, Rabin KR, Raetz EA, Devidas M, Cheng C, Angiolillo A, Baviskar P, Borowitz M, Burke MJ, Carroll A, Carroll WL, Chen IM, Harvey R, Heerema N, Iacobucci I, Wang JR, Jeha S, Larsen E, Mattano L, Maloney K, Pui CH, Ramirez NC, Salzer W, Willman C, Winick N, Wood B, Hunger SP, Wu G, Mullighan CG, Loh ML. Genomic Determinants of Outcome in Acute Lymphoblastic Leukemia. J Clin Oncol. 2024 Oct 10;42(29):3491-3503. doi: 10.1200/JCO.23.02238. Epub 2024 Aug 9.
pmid
39121442
type
DERIVED
citation
Rabin KR, Devidas M, Chen Z, Ji L, Kairalla J, Hitzler JK, Yang JJ, Carroll AJ, Heerema NA, Borowitz MJ, Wood BL, Roberts KG, Mullighan CG, Harvey RC, Chen IM, Willman CL, Reshmi SC, Gastier-Foster JM, Bhojwani D, Rheingold SR, Maloney KW, Mattano LA, Larsen EC, Schore RJ, Burke MJ, Salzer WL, Winick NJ, Carroll WL, Raetz EA, Loh ML, Hunger SP, Angiolillo AL. Outcomes in Children, Adolescents, and Young Adults With Down Syndrome and ALL: A Report From the Children's Oncology Group. J Clin Oncol. 2024 Jan 10;42(2):218-227. doi: 10.1200/JCO.23.00389. Epub 2023 Oct 27.
pmid
37890117
type
DERIVED
citation
Salzer WL, Burke MJ, Devidas M, Dai Y, Hardy KK, Kairalla JA, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Impact of Intrathecal Triple Therapy Versus Intrathecal Methotrexate on Disease-Free Survival for High-Risk B-Lymphoblastic Leukemia: Children's Oncology Group Study AALL1131. J Clin Oncol. 2020 Aug 10;38(23):2628-2638. doi: 10.1200/JCO.19.02892. Epub 2020 Jun 4.
pmid
32496902
type
DERIVED