Therapy for Newly Diagnosed Patients With Acute Lymphobla... | NCT00137111

ID	Type	Link
R37CA036401	U.S. NIH Grant/Contract	View source
P30CA021765	U.S. NIH Grant/Contract	View source
F32CA141762	U.S. NIH Grant/Contract	View source

Name	Class
National Cancer Institute (NCI)	NIH

Description Module

Detailed Description

These are the following secondary objectives:

To determine if CNS irradiation can be safely omitted in the context of the systemic therapy used in the protocol.
To identify whether prolonged (24 hour) intravenous infusions of HDMTX produce greater methotrexate polyglutamate (MTXPG) accumulation than short (4 hour) infusions 42 hours after 1 gm/m2 of HDMTX, stratified for lineage (T- vs B-lineage) and ploidy (hyperdiploid vs non-hyperdiploid B-lineage).
To determine whether prolonged (24 hour) intravenous infusions of HDMTX produce greater antileukemic effects than short (4 hour) infusions, based on the inhibition of de novo purine synthesis in bone marrow blasts and the decrease in circulating blasts during the 4 day "window" prior to initiation of conventional remission induction therapy.
MRD
Other exploratory objectives

Details of Treatment Plan

Treatment will consist of three main phases, Remission Induction, Consolidation, and Continuation. Treatment with an Upfront HDMTX Window for research purposes will be optional.

All patients will receive IT therapy on day 1, dose is age dependent.

Upfront High-Dose Methotrexate Window

HDMTX (1 g/m2) as a 4 hour infusion versus as a 24 hour infusion. Leucovorin rescue will be given.

Remission Induction

Prednisone 40 mg/m2/day PO Days 5 - 32 Vincristine 1.5 mg/m2/week IV Days 5, 12, 19, 26 Daunorubicin 25 mg/m2/week IV Days 5, 12 L-asparaginase 10,000 Unit/m2/dose IM Days 6, 8, 10, 12, 14, 16 (19, 21, 23) Cyclophosphamide 1000 mg/m2/dose IV Day 26 Cytarabine 75 mg/m2/dose IV Days 27-30, 34-37 6-Mercaptopurine 60 mg/m2/dose PO Days 26-39 Imatinib 40 mg/m2 bid for Ph positive patients starting Day 22 of induction. Intrathecal therapy will be administered on day 1 and 19, dose age dependent. Patients with high risk of CNS relapse will receive additional IT treatments on days 8 and 26.

Consolidation Treatment

High dose methotrexate targeted dose depending on risk status, days 1, 15, 29, and 43 and mercaptopurine 50 mg/m2/day, days 1-56.

Reintensification treatment for patients with high risk disease:

Patients with high risk disease will be offered the option of hematopoietic stem cell transplant (HSCT) and may receive an additional 1-2 cycles of reintensification treatment prior to maximize the anti-leukemic kill before transplant.

Dexamethasone 20 mg/m2 PO days 1-3 Cytarabine 2 g/m2 IV x 4 doses, days 3-5 Etoposide 100 mg/m2 IV x 5 doses, days 3-5 L-asparaginase 25,000 Units/m2 IM day 6 Intrathecal treatment Day 5

Continuation Treatment (lasts 120 weeks for girls and 146 weeks for boys)

Treatment will depend on risk classification: low versus standard versus high risk

Treatment weeks 1 to 20:

Week Standard/High Risk Low Risk

DEX + DOX + VCR + 6MP + ASP 6MP + DEX + VCR
6MP + ASP 6MP + MTX
6MP + ASP 6MP + MTX
DEX + DOX + VCR + 6MP + ASP 6MP + DEX + VCR
6MP + ASP 6MP + MTX
6MP + ASP 6MP + MTX
Reinduction I§ Reinduction I
Reinduction I Reinduction I
Reinduction I Reinduction I
6MP + ASP 6MP + MTX
DOX + VCR + 6MP + ASP 6MP + MTX
6MP + ASP 6MP + MTX
6MP + ASP 6MP + MTX
DEX + DOX + VCR + 6MP + ASP 6MP + DEX + VCR
6MP + ASP 6MP + MTX
6MP + ASP 6MP + MTX
Reinduction II Reinduction II
Reinduction II Reinduction II
Reinduction II Reinduction II
No chemotherapy 6MP + MTX

Dexamethasone 12 mg/m2 (std/high risk) or 8 mg/m2 (low risk) PO daily (tid) x 5 days, Days 1-5 Doxorubicin 30 mg/m2 IV, Day 1 Vincristine 2.0 mg/m2 IV push (max. 2 mg), Day 1 Mercaptopurine 50 mg/m2 PO daily x 7 days (std/high risk), Days 1-7 75 mg/m2 PO daily x 7 days (low risk), Days 1-7 L-asparaginase 25,000 Unit/m2 IM, Day 1 Methotrexate 40 mg/m2 IV or IM, Day 1

Reinduction I and II

This phase of treatment will be started at weeks 7 and 17 after bone marrow examination confirms complete remission. Reinduction treatment will be given twice: weeks 7 to 9 and weeks 17 to 19 for all patients.

Reinduction I for Standard/High Risk ALL:

Dexamethasone 8 mg/m2/day PO (t.i.d.) Days 1-8, 15, 21, Vincristine 1.5 mg/m2/week IV (max 2 mg) Days 1, 8, 15, Doxorubicin 30 mg/m2 Days 1, 8, L-asparaginase 25,000 Unit/m2 IM Days 1, 8, 15, Intrathecal chemotherapy, dose age dependent Day 1.

Reinduction II for Standard/High Risk ALL:

Dexamethasone 8 mg/m2/day PO (t.i.d.) Days 1-8, 15-21, Vincristine 1.5 mg/m2/week IV (max 2 mg) Days 1, 8, 15, L-asparaginase 25,000 Unit/m2, weekly IM Days 1, 8, 17, Intrathecal chemotherapy, dose age dependent Day 1 High-dose cytarabine 2 gm/m2 IV q 12 Days 15, 16

Reinduction I and II for Low Risk ALL Dexamethasone 8 mg/m2/day PO (t.i.d.) Days 1-8, 15-21 Vincristine 1.5 mg/m2/week IV (max 2 mg), Days 1, 8, 15 L-asparaginase 10,000 Unit/m2/thrice weekly IM Days 2, 4, 6, 8, 10, 12, 15, 17, 19 Doxorubicin 30 mg/m2/week IV Day 1 Intrathecal chemotherapy, dose age dependent on Day 1

Treatment Weeks 21 to end of therapy Week Standard/High Risk Low Risk
6MP + MTX 6MP + MTX
6MP + MTX 6MP + MTX
Cyclo + Ara-C 6MP + MTX
DEX + VCR 6MP + DEX + VCR
6MP + MTX 6MP + MTX
6MP + MTX 6MP + MTX
Cyclo + Ara-C 6MP + MTX
DEX + VCR 6MP + DEX + VCR

Mercaptopurine 75 mg/m2 PO, daily x 7 days, Days 1-7 Methotrexate 40 mg/m2 IV or IM, Day 1 Cyclophosphamide 300 mg/m2 IV, Day 1 Cytarabine 300 mg/m2 IV, Day 1 Dexamethasone 12 mg/m2 (std/high risk) or 8 mg/m2 (low risk) PO daily (tid) x 5, Day 1-5 Vincristine 2.0 mg/m2 IV push (max. 2 mg), Day 1

The same treatment (weeks 21-28) will be repeated for a total of 6 times (until week 68). After week 68, all patients will receive daily 6MP and weekly MTX with pulses of dexamethasone and vincristine every 4 weeks until week 100, after which only 6MP and methotrexate will be given. Intrathecal treatment will be given every 8 weeks only to patients at high risk of CNS relapse after week 48 and will be discontinued after week 96. Continuation therapy will be discontinued after 120 weeks in girls and after 146 weeks in boys

Patients who meet the criteria of high-risk ALL are candidates for allogeneic hematopoietic stem cell transplantation. However, if the option is declined by the patients or guardians, or the procedure is deemed unsuitable by the attending physician and the principal investigator, the patient will remain on study and continue to receive chemotherapy

Label	Type	Description	Intervention Names
1	Other		Drug: Prednisone, Dexamethasone, Vincristine, Daunorubicin Drug: Doxorubicin, L-asparaginase, PEG-L-asparaginase, Erwinia asparaginase Drug: Methotrexate, Cyclophosphamide, Cytarabine, Etoposide Drug: Mercaptopurine, Imatinib Procedure: chemotherapy, intrathecal chemotherapy Procedure: steroid therapy, hematopoietic stem cell transplantation
2	Other		Drug: Prednisone, Dexamethasone, Vincristine, Daunorubicin Drug: Doxorubicin, L-asparaginase, PEG-L-asparaginase, Erwinia asparaginase Drug: Methotrexate, Cyclophosphamide, Cytarabine, Etoposide Drug: Mercaptopurine, Imatinib Procedure: chemotherapy, intrathecal chemotherapy Procedure: steroid therapy, hematopoietic stem cell transplantation

Name	Type	Description	Arm Group Labels	Other Names
Prednisone, Dexamethasone, Vincristine, Daunorubicin	Drug	See Detailed Description sections for details on treatment interventions.	1 2

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Overall Event-free Survival (EFS)	EFS was measured from the start of on-study to the date of first treatment failure of any kind (relapse, death, lineage switch, or second malignancy) or to the last date of follow-up. Failure to enter remission was considered an event at time zero. Measurement was determined by Kaplan-Meyer estimate.	Median follow-up time (range) 5.6 (1.3 to 8.9) years
Continuous Complete Remission Since Week 56 Therapy.	CCR was measured from end of week 56 therapy to the date of first treatment failure of any kind (relapse, death, lineage switch, or second malignancy) or to the last date of follow-up. Measurement was determined by Kaplan-Meyer estimate.	Median follow up time (range) 4.5 (1 to 7.8) years

Secondary Outcomes

Measure	Description	Time Frame
Minimal Residual Disease (MRD)	Detection of MRD at end of induction where positive MRD was defined as one or more leukemic cell per 10,000 mononuclear bone-marrow cells (>=0.01%).	End of Induction (Day 46 MRD measurement)
Mean Difference of Active Methotrexate Polyglutamates (MTXPG) in Leukemia Cells Between Two Arms (4 Hours vs. 24 Hours).

Other Outcomes

Measure	Description	Time Frame
Median Difference in CASP1 Gene Expression in Primary Leukemia Cells of Patients in Glucocorticoid-resistant Cells vs Glucocorticoid-sensitive Cells	Prednisolone sensitivity was measured in primary leukemia cells from bone marrow collected at diagnosis. Expression of CASP1 was determined by HG-U133A microarray. Values given are gene expression values, and the unit is arbitrary units (AU) defined as scaled fluorescence measured on microarray.

Name	Affiliation	Role
Ching-Hon Pui, M.D.	St. Jude Children's Research Hospital	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
St Jude Children's Research Hospital		Memphis	Tennessee	38105	United States
Cook Children's Medical Center

PubMed Identifier	Type	Citation	Retractions
12086872	Background	Yeoh EJ, Ross ME, Shurtleff SA, Williams WK, Patel D, Mahfouz R, Behm FG, Raimondi SC, Relling MV, Patel A, Cheng C, Campana D, Wilkins D, Zhou X, Li J, Liu H, Pui CH, Evans WE, Naeve C, Wong L, Downing JR. Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell. 2002 Mar;1(2):133-43. doi: 10.1016/s1535-6108(02)00032-6.
12239148	Background	Coustan-Smith E, Sancho J, Hancock ML, Razzouk BI, Ribeiro RC, Rivera GK, Rubnitz JE, Sandlund JT, Pui CH, Campana D. Use of peripheral blood instead of bone marrow to monitor residual disease in children with acute lymphoblastic leukemia. Blood. 2002 Oct 1;100(7):2399-402. doi: 10.1182/blood-2002-04-1130.

Label	URL
St Jude Children's Research Hospital	View source

ID	Title	Description
FG000	Total Therapy	Total therapy applies to all eligible patients and includes remission induction, consolidation, and continuation therapy.
FG001	4 hr	4 hour High-Dose Methotrexate Infusion in upfront window treatment

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Overall Event-free Survival (EFS)

EFS was measured from the start of on-study to the date of first treatment failure of any kind (relapse, death, lineage switch, or second malignancy) or to the last date of follow-up. Failure to enter remission was considered an event at time zero. Measurement was determined by Kaplan-Meyer estimate.

498 enrolled patients were eligible for analysis to estimate the overall event-free survival of children at least one year of age at diagnosis who are treated with risk-directed therapy.

Posted

Number

Percentage of Participants

Median follow-up time (range) 5.6 (1.3 to 8.9) years

ID	Title	Description
OG000	Total Therapy	Total therapy applies to all eligible patients.

Units	Counts
Participants	OG000498

Title

Denominators

Categories

Title	Measurements
	OG00087.3(.831 to .901)

Primary

Continuous Complete Remission Since Week 56 Therapy.

CCR was measured from end of week 56 therapy to the date of first treatment failure of any kind (relapse, death, lineage switch, or second malignancy) or to the last date of follow-up. Measurement was determined by Kaplan-Meyer estimate.

Patients meeting the following high risk CNS Relapse criteria: white cell blood cell count at diagnosis more than 100,000; Philadelphia Chromosome Positive; CNS 3 at diagnosis; T-Lineage with white blood cell count more than 50,000.

Posted

Number

Percentage of participants

Median follow up time (range) 4.5 (1 to 7.8) years

ID	Title	Description
OG000	Patients With High Risk of CNS Relapse	This is a subset of all patients enrolled. It is not a specific treatment arm.

Units	Counts
Participants	OG000

Secondary

Minimal Residual Disease (MRD)

Detection of MRD at end of induction where positive MRD was defined as one or more leukemic cell per 10,000 mononuclear bone-marrow cells (>=0.01%).

Patients who completed induction and had successful MRD studies on day 46.

Posted

Number

participants

End of Induction (Day 46 MRD measurement)

ID	Title	Description
OG000	Total Therapy	Total therapy applies to all eligible patients.

Units	Counts
Participants	OG000492

Secondary

Mean Difference of Active Methotrexate Polyglutamates (MTXPG) in Leukemia Cells Between Two Arms (4 Hours vs. 24 Hours).

Children were randomly assigned to receive initial single-agent treatment with HDMTX (1g/m^2) as either a 24-hour infusion or a 4-hour infusion and the outcome measure was the accumulation of MTXPG in leukemia cells.

The 286 patients randomized to treatment with high-dose methotrexate (HDMTX) who had methotrexate polyglutamate (MTXPG) concentration measured in bone marrow ALL cells .

Posted

Mean

Standard Deviation

pmol/1,000,000,000 cells

42 hours after start of high dose methotrexate infusion (HDMTX)

ID	Title	Description
OG000	4 hr	4 hour High-Dose Methotrexate Infusion in upfront window treatment
OG001	24 hr	24 hour High-Dose Methotrexate Infusion in upfront window treatment

Units	Counts
Participants	OG000

Secondary

Circulating Leukemia Cells in Peripheral Blood Change From Prior to the Methotrexate Infusion to Three Days After Between Two Arms (4 Hours vs. 24 Hours)

White blood cell (leukocytes) counts in peripheral blood by Complete Blood Count

Measurement: Percentage change of leukemia cells from baseline

Three hundred twenty (320) patients were evaluable to assess the influence of infusion duration on methotrexate's antileukemic effects.

Posted

Mean

Standard Deviation

Percent change

Immediately before the methotrexate infusion and three days after subsequent infusion

ID	Title	Description
OG000	4 hr	4 hour High-Dose Methotrexate Infusion in upfront window treatment
OG001	24 hr	24 hour High-Dose Methotrexate Infusion in upfront window treatment

Units	Counts
Participants	OG000

Other Pre-specified

Median Difference in CASP1 Gene Expression in Primary Leukemia Cells of Patients in Glucocorticoid-resistant Cells vs Glucocorticoid-sensitive Cells

Prednisolone sensitivity was measured in primary leukemia cells from bone marrow collected at diagnosis. Expression of CASP1 was determined by HG-U133A microarray. Values given are gene expression values, and the unit is arbitrary units (AU) defined as scaled fluorescence measured on microarray.

One hundred forty-four (144) patients were evaluable to assess prednisolone sensitivity measured in bone marrow ALL cells and CASP1 expression in RNA by MTT assay.

Posted

Median

Inter-Quartile Range

arbitrary units

Pre-treatment

ID	Title	Description
OG000	Total Therapy	Total therapy applies to all eligible patients.

Units	Counts
Participants	OG000

Other Pre-specified

Median Difference in NLRP3 Gene Expression in Primary Leukemia Cells of Patients in Glucocorticoid-resistant Cells vs. Glucocorticoid-sensitive Cells

Prednisolone sensitivity was measured in primary leukemia cells from bone marrow collected at diagnosis. Expression of NLRP3 was determined by HG-U133A microarray. Values given are gene expression values, and the unit is arbitrary units (AU) defined as scaled fluorescence measured on microarray.

One hundred forty-four (144) patients were evaluable to assess prednisolone sensitivity measured in bone marrow ALL cells and NLRP3 expression in RNA by MTT assay

Posted

Median

Inter-Quartile Range

arbitrary units

Pre-treatment

ID	Title	Description
OG000	Total Therapy	Total therapy applies to all eligible patients.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acidosis (metabolic or respiratory)	Metabolism and nutrition disorders	CTCAE (2.0)	Non-systematic Assessment	EG0002 events2 affected498 at risk
Adult respiratory distress syndrome (ARDS)	Respiratory, thoracic and mediastinal disorders	CTCAE (2.0)	Non-systematic Assessment	EG00011 events11 affected498 at risk
Allergic Reaction to Asparaginase	Immune system disorders	CTCAE (2.0)	Non-systematic Assessment	EG0006 events6 affected498 at risk
Allergic reaction/hypersensitivity (including drug fever)	Immune system disorders	CTCAE (2.0)	Non-systematic Assessment	EG0002 events2 affected498 at risk
Amylase	Metabolism and nutrition disorders	CTCAE (2.0)	Non-systematic Assessment	EG0001 events1 affected498 at risk
Apnea	Respiratory, thoracic and mediastinal disorders	CTCAE (2.0)	Non-systematic Assessment	EG0002 events2 affected498 at risk
Bilirubin	Hepatobiliary disorders	CTCAE (2.0)	Non-systematic Assessment	EG0001 events1 affected498 at risk
CNS hemorrhage/bleeding	Blood and lymphatic system disorders	CTCAE (2.0)	Non-systematic Assessment	EG0002 events2 affected498 at risk
Catheter-related infection	Infections and infestations	CTCAE (2.0)	Non-systematic Assessment	EG0003 events3 affected498 at risk
Colitis	Gastrointestinal disorders	CTCAE (2.0)	Non-systematic Assessment	EG0004 events4 affected498 at risk
Creatinine	Renal and urinary disorders	CTCAE (2.0)	Non-systematic Assessment	EG0001 events1 affected498 at risk
DIC (disseminated intravascular coagulation)	Blood and lymphatic system disorders	CTCAE (2.0)	Non-systematic Assessment	EG0002 events2 affected498 at risk
Dermatology/Skin-Other	Skin and subcutaneous tissue disorders	CTCAE (2.0)	Non-systematic Assessment	EG0001 events1 affected498 at risk
Dyspnea (shortness of breath)	Respiratory, thoracic and mediastinal disorders	CTCAE (2.0)	Non-systematic Assessment	EG0002 events2 affected498 at risk
Edema	General disorders	CTCAE (2.0)	Non-systematic Assessment	EG0002 events2 affected498 at risk
Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infe	Infections and infestations	CTCAE (2.0)	Non-systematic Assessment	EG0004 events3 affected498 at risk
Fever (in the absence of neutropenia, where neutropenia is defined as AGC<1.0 x 10e9/L)	General disorders	CTCAE (2.0)	Non-systematic Assessment	EG0003 events3 affected498 at risk
Hemorrhage/bleeding with grade 3 or 4 thrombocytopenia	Blood and lymphatic system disorders	CTCAE (2.0)	Non-systematic Assessment	EG0001 events1 affected498 at risk
Hepatic-Other	Hepatobiliary disorders	CTCAE (2.0)	Non-systematic Assessment	EG0001 events1 affected498 at risk
Hyperglycemia	Metabolism and nutrition disorders	CTCAE (2.0)	Non-systematic Assessment	EG0001 events1 affected498 at risk
Hyperkalemia	Metabolism and nutrition disorders	CTCAE (2.0)	Non-systematic Assessment	EG0001 events1 affected498 at risk
Hypertension	Cardiac disorders	CTCAE (2.0)	Non-systematic Assessment	EG0002 events2 affected498 at risk
Hypotension	Cardiac disorders	CTCAE (2.0)	Non-systematic Assessment	EG0009 events9 affected498 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	CTCAE (2.0)	Non-systematic Assessment	EG00010 events10 affected498 at risk
Infection (documented clinically or microbiologically) with grade 3 or 4 neutropenia (ANC <1.0 x 10e	Infections and infestations	CTCAE (2.0)	Non-systematic Assessment	EG00032 events32 affected498 at risk
Infection without neutropenia	Infections and infestations	CTCAE (2.0)	Non-systematic Assessment	EG0005 events5 affected498 at risk
Leukoencephalopathy associated with radiological findings	Nervous system disorders	CTCAE (2.0)	Non-systematic Assessment	EG0002 events2 affected498 at risk
Lipase	Metabolism and nutrition disorders	CTCAE (2.0)	Non-systematic Assessment	EG0001 events1 affected498 at risk
Liver dysfunction/failure (clinical),	Hepatobiliary disorders	CTCAE (2.0)	Non-systematic Assessment	EG0002 events2 affected498 at risk
Neuropathy-sensory	Nervous system disorders	CTCAE (2.0)	Non-systematic Assessment	EG0001 events1 affected498 at risk
Pancreatitis	Gastrointestinal disorders	CTCAE (2.0)	Non-systematic Assessment	EG0002 events2 affected498 at risk
Personality/behavioral	Psychiatric disorders	CTCAE (2.0)	Non-systematic Assessment	EG0001 events1 affected498 at risk
Pleural effusion (non-malignant)	Respiratory, thoracic and mediastinal disorders	CTCAE (2.0)	Non-systematic Assessment	EG0004 events4 affected498 at risk
Pneumonitis/pulmonary infiltrates	Respiratory, thoracic and mediastinal disorders	CTCAE (2.0)	Non-systematic Assessment	EG0003 events3 affected498 at risk
Pulmonary-Other	Respiratory, thoracic and mediastinal disorders	CTCAE (2.0)	Non-systematic Assessment	EG0001 events1 affected498 at risk
Renal failure	Gastrointestinal disorders	CTCAE (2.0)	Non-systematic Assessment	EG0004 events4 affected498 at risk
Seizure(s)	Nervous system disorders	CTCAE (2.0)	Non-systematic Assessment	EG0006 events6 affected498 at risk
Sinus tachycardia	Cardiac disorders	CTCAE (2.0)	Non-systematic Assessment	EG0001 events1 affected498 at risk
Supraventricular arrhythmias (SVT/atrial fibrillation/flutter)	Cardiac disorders	CTCAE (2.0)	Non-systematic Assessment	EG0001 events1 affected498 at risk
Thrombosis/embolism	Cardiac disorders	CTCAE (2.0)	Non-systematic Assessment	EG0005 events5 affected498 at risk
Typhlitis (inflammation of cecum)	Gastrointestinal disorders	CTCAE (2.0)	Non-systematic Assessment	EG0002 events2 affected498 at risk
Vision-blurred vision	Eye disorders	CTCAE (2.0)	Non-systematic Assessment	EG0001 events1 affected498 at risk
Vomiting	Gastrointestinal disorders	CTCAE (2.0)	Non-systematic Assessment	EG0001 events1 affected498 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain or cramping	General disorders	CTCAE (2.0)	Non-systematic Assessment	EG00069 events47 affected498 at risk
Allergic Reaction to Asparaginase	Immune system disorders	CTCAE (2.0)	Non-systematic Assessment	EG00045 events41 affected498 at risk
Anorexia	Gastrointestinal disorders	CTCAE (2.0)	Non-systematic Assessment	EG00031 events26 affected498 at risk
Catheter-related infection	Infections and infestations	CTCAE (2.0)	Non-systematic Assessment	EG000131 events86 affected498 at risk
Dehydration	Gastrointestinal disorders	CTCAE (2.0)	Non-systematic Assessment	EG00036 events29 affected498 at risk
Diarrhea patients without colostomy	Gastrointestinal disorders	CTCAE (2.0)	Non-systematic Assessment	EG00062 events53 affected498 at risk
Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infe	Infections and infestations	CTCAE (2.0)	Non-systematic Assessment	EG0001,407 events436 affected498 at risk
Fever (in the absence of neutropenia, where neutropenia is defined as AGC<1.0 x 10e9/L)	General disorders	CTCAE (2.0)	Non-systematic Assessment	EG000403 events208 affected498 at risk
Headache	General disorders	CTCAE (2.0)	Non-systematic Assessment	EG00038 events26 affected498 at risk
Hyperglycemia	Metabolism and nutrition disorders	CTCAE (2.0)	Non-systematic Assessment	EG00062 events43 affected498 at risk
Hypertension	Cardiac disorders	CTCAE (2.0)	Non-systematic Assessment	EG00042 events42 affected498 at risk
Hypokalemia	Metabolism and nutrition disorders	CTCAE (2.0)	Non-systematic Assessment	EG00036 events32 affected498 at risk
Hypotension	Cardiac disorders	CTCAE (2.0)	Non-systematic Assessment	EG00053 events52 affected498 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	CTCAE (2.0)	Non-systematic Assessment	EG00062 events51 affected498 at risk
Infection (documented clinically or microbiologically) with grade 3 or 4 neutropenia	Infections and infestations	CTCAE (2.0)	Non-systematic Assessment	EG000893 events379 affected498 at risk
Infection without neutropenia	Infections and infestations	CTCAE (2.0)	Non-systematic Assessment	EG000594 events290 affected498 at risk
Neuropathic pain	Nervous system disorders	CTCAE (2.0)	Non-systematic Assessment	EG00046 events46 affected498 at risk
Osteonecrosis	Musculoskeletal and connective tissue disorders	CTCAE (2.0)	Non-systematic Assessment	EG00060 events35 affected498 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	CTCAE (2.0)	Non-systematic Assessment	EG00025 events25 affected498 at risk
Pneumonitis/pulmonary infiltrates	Respiratory, thoracic and mediastinal disorders	CTCAE (2.0)	Non-systematic Assessment	EG00033 events29 affected498 at risk
SGPT (ALT)	Hepatobiliary disorders	CTCAE (2.0)	Non-systematic Assessment	EG000100 events76 affected498 at risk
Stomatitis/pharyngitis (oral/pharyngeal mucositis),	Gastrointestinal disorders	CTCAE (2.0)	Non-systematic Assessment	EG00075 events65 affected498 at risk
Thrombosis/embolism	Cardiac disorders	CTCAE (2.0)	Non-systematic Assessment	EG00034 events31 affected498 at risk
Typhlitis	Gastrointestinal disorders	CTCAE (2.0)	Non-systematic Assessment	EG00037 events27 affected498 at risk
Vomiting	Gastrointestinal disorders	CTCAE (2.0)	Non-systematic Assessment	EG00067 events59 affected498 at risk
Wound-infectious	Skin and subcutaneous tissue disorders	CTCAE (2.0)	Non-systematic Assessment	EG00048 events43 affected498 at risk

Ancestor Terms

ID	Term
D011244	Pregnadienediols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D011246	Pregnadienetriols
D013259	Steroids, Fluorinated
D014748	Vinca Alkaloids
D046948	Secologanin Tryptamine Alkaloids
D026121	Indole Alkaloids
D000470	Alkaloids
D006571	Heterocyclic Compounds
D007211	Indoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D054836	Indolizidines
D007212	Indolizines
D018943	Anthracyclines
D009279	Naphthacenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D000617	Aminoglycosides
D006027	Glycosides
D002241	Carbohydrates
D000581	Amidohydrolases
D006867	Hydrolases
D004798	Enzymes
D045762	Enzymes and Coenzymes
D000630	Aminopterin
D011622	Pterins
D011621	Pteridines
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D063088	Phosphoramides
D009943	Organophosphorus Compounds
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D001087	Arabinonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
D011034	Podophyllotoxin
D013764	Tetrahydronaphthalenes
D009281	Naphthalenes
D005960	Glucosides
D013438	Sulfhydryl Compounds
D013457	Sulfur Compounds
D011687	Purines
D001549	Benzamides
D000577	Amides
D001565	Benzoates
D000146	Acids, Carbocyclic
D002264	Carboxylic Acids
D001555	Benzene Derivatives
D010879	Piperazines
D013812	Therapeutics
D033581	Stem Cell Transplantation
D017690	Cell Transplantation
D064987	Cell- and Tissue-Based Therapy
D001691	Biological Therapy
D014180	Transplantation
D013514	Surgical Procedures, Operative

ID	Term
D007945	Leukemia, Lymphoid
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

ID	Term
D011241	Prednisone
D003907	Dexamethasone
D014750	Vincristine
D003630	Daunorubicin
D004317	Doxorubicin
D001215	Asparaginase
C042705	pegaspargase
C000718243	asparaginase erwinia chrysanthemi recombinant
D008727	Methotrexate
D003520	Cyclophosphamide
D003561	Cytarabine
D005047	Etoposide
D015122	Mercaptopurine
D000068877	Imatinib Mesylate
D004358	Drug Therapy
D018380	Hematopoietic Stem Cell Transplantation

ID	Title	Description
BG000	Total Therapy	Total therapy applies to all eligible patients and includes remission induction, consolidation, and continuation therapy.
BG001	4 hr	4 hour High-Dose Methotrexate Infusion in upfront window treatment
BG002	24 hr	24 hour High-Dose Methotrexate Infusion in upfront window treatment
BG003	Non Randomized	Patients not randomized for window study
BG004	Total	Total of all reporting groups

ID	Term
D054198	Precursor Cell Lymphoblastic Leukemia-Lymphoma
D007938	Leukemia