NCT00408005 · CITED IN SOURCE DOCUMENTS

Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma

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: 2026-06-23

This randomized phase III trial is studying different combination chemotherapy regimens and their side effects and comparing how well they work in treating young patients with newly diagnosed T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma. After a common induction therapy, patients were risk assigned and eligible for one or both post-induction randomizations: Escalating dose Methotrexate versus High Dose Methotrexate in Interim Maintenance therapy, No Nelarabine versus Nelarabine in Consolidation therapy. T-ALL patients are risk assigned as Low Risk, Intermediate Risk or High Risk. Low Risk patients are not eligible for the Nelarabine randomization, Patients with CNS disease at diagnosis were assgined to receive High Dose Methotrexate, patients who failed induction therapy were assigned to receive Nelarabine and High Dose Methotrexate. T-LLy patients were all assigned to escalating dose Methotrexate and were risk assigned as Standard Risk, High Risk and induction failures. Standard risk patients did not receive nelarabine, High risk T-LLy patients were randomized to No Nelarabine versus Nelarabine, and Induction failures were assigned to receive Nelarabine.

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

Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV)

→

outcome · POSTED

Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I + Arm III vs. Arm II + Arm IV)

→

outcome · POSTED

Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV)

→

outcome · POSTED

Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I + Arm II vs. Arm III + Arm IV)

→

outcome · POSTED

Disease-free Survival (DFS) for T-cell Lymphoblastic Lymphoma (T-LLy) Cohort

→

outcome · POSTED

Cumulative Incidence of CNS Relapse for T-ALL by Risk Group

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

eligibility Criteria: Inclusion Criteria: * T-ALL patients must be enrolled on AALL08B1 prior to treatment and enrollment on AALL0434 * Patients must have newly diagnosed T-ALL or T-lineage lymphoblastic lymphoma (T-NHL) stage II-IV; B-lineage lymphoblastic lymphoma will not be eligible for this study; a diagnosis of T-ALL is established when leukemic blasts lack myeloperoxidase or evidence of B-lineage derivation (cluster of differentiation \[CD\]19/CD22/CD20), and express either surface or cytoplasmic CD3 or two or more of the antigens CD8, CD7, CD5, CD4, CD2 or CD1a; if surface CD3 is expressed on all leukemic cells, additional markers of immaturity, including transmission disequilibrium test (TdT), CD34 or CD99 will be assessed for expression; cases with uncertain expression will receive additional review within the appropriate Children's Oncology Group (COG) reference laboratory * T-NHL PATIENTS: * For T-NHL patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to T-ALL; for tissue processed by other means (i.e. paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of T-NHL defined by the submitting institution will be accepted * Prior therapy restrictions * Patients shall have had no prior cytotoxic chemotherapy with the exception of steroids and/or IT cytarabine * IT chemotherapy with cytarabine is allowed prior to registration for patient convenience; this is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture; (Note: the CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment); systemic chemotherapy must begin within 72 hours of this IT therapy * Patients diagnosed as having T-NHL or T-ALL with respiratory distress or hyperleukocytosis may require steroids prior to the initiation of additional systemic therapy; they are eligible for AALL0434 and will be stratified, based on the initial complete blood count (CBC); steroid pretreatment may alter the risk group assessment; if the T-ALL patient's clinical status precludes a lumbar puncture within 48 hours of the initiation of steroid therapy, T-ALL patients CANNOT be classified as low risk and will be Intermediate or high risk based on the results of the day 29 marrow as above; patients with T-NHL who receive steroid pre-treatment will be classified as high risk; the dose and duration of previous steroid therapy should be carefully documented * For the management of airway compromise, patients who have received emergent chest irradiation up to 600 cGy will be eligible for this study * Patients with a prior seizure disorder requiring anti-convulsant therapy are not eligible to receive nelarabine; in addition, patients with pre-existing grade 2 (or greater) peripheral neurotoxicity, as determined prior to Induction treatment by the treating physician or a neurologist, are not eligible to receive nelarabine; these restrictions in eligibility are designed to prevent excessive nelarabine-induced central and peripheral neurotoxicity in at-risk patients; for the purposes of this study, this includes any patient that has received anticonvulsant therapy to prevent/treat seizures in the prior two years Exclusion Criteria: * Pregnant or lactating females are ineligible * Patients with Down syndrome are ineligible to enroll onto this study * For T-NHL patients the following additional exclusion criteria apply: * B-precursor lymphoblastic lymphoma * Morphologically unclassifiable lymphoma * Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma * CNS3-positive or testicular involvement
healthy Volunteers: false
maximum Age: 30 Years
minimum Age: 1 Year
sex: ALL
std Ages: CHILD
ADULT

Treatment arms and interventions

arm Groups

description
All patients (T-ALL and T-LLy) receive cytarabine intrathecally (IT) on day 1; vincristine sulfate IV on days 1, 8, 15, and 22; prednisone IV or PO twice daily BID on days 1-28; pegaspargase IM (may give IV over 1 to 2 hours) on day 4, 5, or 6; daunorubicin hydrochloride IV on days 1, 8, 15 and 22; and methotrexate IT on days 8 and 29 (and days 15 and 22 for patients with CNS3 disease).
intervention Names
Drug: Cytarabine
Drug: Daunorubicin Hydrochloride
Drug: Methotrexate
Drug: Pegaspargase
Drug: Prednisone
Drug: Vincristine Sulfate
label
Group 0 Induction Therapy
type
EXPERIMENTAL
description
Patients receive nelarabine IV over 60 minutes on days 1-5 and 43-47; methotrexate IT on days 15, 22, 57, and 64; cyclophosphamide IV over 30 minutes on days 8 and 50; cytarabine IV over 15-30 minutes or SC on days 8-11, 15-18, 50-53 and 57-60; mercaptopurine PO on days 8-21 and 50-63; vincristine sulfate IV on days 22, 29, 64, and 71; and pegaspargase IM or IV over 1-2 hours on days 22 and 64. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 15, 22-26, and 29-33 (DS patients excluded as of 09/29/10). (Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT QD on days 22-28 and 29-35.
intervention Names
Drug: Cyclophosphamide
Drug: Cytarabine
Drug: Mercaptopurine
Drug: Methotrexate
Drug: Nelarabine
Drug: Pegaspargase
Radiation: Radiation Therapy
label
Group 1 Arm IV (Consolidation chemotherapy)
type
ACTIVE_COMPARATOR
description
Patients receive methotrexate IT on days 1, 8, 15, and 22; cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine IV over 15-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO on days 1-14 and 29-42; vincristine sulfate IV on days 15, 22, 43 and 50; and pegaspargase IM or IV over 1-2 hours on days 15 and 43. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 11-12, 15-19, and 22-26. (DS patients excluded as of 09/29/10.) Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT (1,200 cGy/dose) QD on days 15-21 and 22-28. Patients with low-risk disease do not undergo CRT. Patients with standard risk T-LLy received Arm I, and those with high risk T-LLy were randomized between Arm I and Arm II combination chemotherapy.
intervention Names
Drug: Cyclophosphamide
Drug: Cytarabine
Drug: Leucovorin Calcium
Drug: Mercaptopurine
Drug: Methotrexate
Drug: Pegaspargase
Radiation: Radiation Therapy
Drug: Vincristine Sulfate
label
Group I Arm I (Consolidation chemotherapy)
type
ACTIVE_COMPARATOR
description
Patients receive vincristine sulfate IV on days 1, 8, 15, 43, and 50; dexamethasone IV or PO BID on days 1-21 (for patients \< 10 years of age) OR on days 1-7 and 15-21 (for patients \>= 10 years of age and for patients with DS); doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6, AND day 43; methotrexate IT on days 1, 29, and 36; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV over 15-30 minutes or SC on days 29-32 and 36-39; and thioguanine PO on days 29-42. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose (DS patients excluded as of 09/29/10). Standard risk T-LLy patients were assigned to Arm I and those with high risk were randomized between Arm I and Arm II.
intervention Names
Drug: Cyclophosphamide
Drug: Cytarabine
Drug: Dexamethasone
Drug: Doxorubicin Hydrochloride
Drug: Leucovorin Calcium
Drug: Methotrexate
Drug: Pegaspargase
Drug: Thioguanine
Drug: Vincristine Sulfate
label
Group I Arm I (Delayed intensification chemotherapy
type
ACTIVE_COMPARATOR
description
Patients receive vincristine sulfate IV on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61; mercaptopurine PO QD on days 1-84; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; and methotrexate IT on day 1. Treatment repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 119) (for girls with T-ALL), all patients with T-LLy, and 3 years from the start of interim maintenance therapy (approximately week 171) (for boys with T-ALL).
intervention Names
Other: Laboratory Biomarker Analysis
Drug: Mercaptopurine
Drug: Methotrexate
Drug: Prednisone
Drug: Vincristine Sulfate
label
Group I Arm I (Maintenance chemotherapy)
type
ACTIVE_COMPARATOR
description
Patients receive vincristine sulfate IV and escalating doses of methotrexate IV on days 1, 11, 21, 31, and 41; pegaspargase\* IM or IV over 1-2 hours on days 2 and 22; and methotrexate IT on days 1 and 31. Patients with DS also receive leucovorin calcium PO 48 and 60 hours after each methotrexate IT dose (DS patients excluded as of 09/29/10). Note: \*Patients with an allergy to pegaspargase receive Erwinia asparaginase on days 2, 4, 6, 8, 10, 12, 22, 24, 26, 28, 30, and 32.
intervention Names
Drug: Leucovorin Calcium
Drug: Methotrexate
Drug: Pegaspargase
Drug: Vincristine Sulfate
label
Group I Arm I (Interim maintenance chemotherapy)
type
ACTIVE_COMPARATOR
description
Patients receive nelarabine IV over 60 minutes on days 1-5 and 43-47; methotrexate IT on days 15, 22, 57, and 64; cyclophosphamide IV over 30 minutes on days 8 and 50; cytarabine IV over 15-30 minutes or SC on days 8-11, 15-18, 50-53 and 57-60; mercaptopurine PO on days 8-21 and 50-63; vincristine sulfate IV on days 22, 29, 64, and 71; and pegaspargase IM or IV over 1-2 hours on days 22 and 64. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 15, 22-26, and 29-33 (DS patients excluded as of 09/29/10). (Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT QD on days 22-28 and 29-35. Patients with high risk T-LLy were either randomized to Arm I or Arm II. Patients with T-LLy who failed induction therapy were assigned to Arm II.
intervention Names
Drug: Cyclophosphamide
Drug: Cytarabine
Drug: Mercaptopurine
Drug: Methotrexate
Drug: Nelarabine
Drug: Pegaspargase
Radiation: Radiation Therapy
Drug: Vincristine Sulfate
label
Group I Arm II (Consolidation chemotherapy)
type
ACTIVE_COMPARATOR
description
Patients receive vincristine sulfate IV on days 1, 8, 15, and 50; dexamethasone IV or PO BID on days 1-21 (for patients \< 10 years of age) OR on days 1-7 and 15-21 (for patients \>= 10 years of age); doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6 AND day 50; methotrexate IT on days 1, 36, and 43; nelarabine IV over 60 minutes on days 29-33; cyclophosphamide IV over 30 minutes on day 36; cytarabine IV over 15-30 minutes or SC on days 36-39 and 43-46; and thioguanine PO on days 36-49.
intervention Names
Drug: Cyclophosphamide
Drug: Cytarabine
Drug: Dexamethasone
Drug: Doxorubicin Hydrochloride
Drug: Nelarabine
Drug: Pegaspargase
Drug: Thioguanine
Drug: Vincristine Sulfate
label
Group I Arm II (Delayed intensification chemotherapy)
type
ACTIVE_COMPARATOR
description
Patients receive vincristine sulfate IV and escalating doses of methotrexate IV on days 1, 11, 21, 31, and 41; pegaspargase\* IM or IV over 1-2 hours on days 2 and 22; and methotrexate IT on days 1 and 31. Note: \*Patients with an allergy to pegaspargase receive Erwinia asparaginase on Monday, Wednesday and Friday for two consecutive weeks starting the day of asparaginase substitution.
intervention Names
Drug: Asparaginase
Drug: Methotrexate
Drug: Pegaspargase
Drug: Vincristine Sulfate
label
Group I Arm II (Interim maintenance chemotherapy)
type
ACTIVE_COMPARATOR
description
Patients receive vincristine sulfate, prednisone, mercaptopurine, methotrexate PO, methotrexate IT, and nelarabine in Cycles 1, 2 and 3. Patients then receive treatment (without nelarabine) as follows: vincristine sulfate, prednisone, mercaptopurine, methotrexate PO, and methotrexate IT as in arm II. Treatment (without nelarabine) repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 121) (for girls with T-ALL), and for those with T-LLY, and 3 years from the start of interim maintenance therapy (approximately week 173) (for boys with T-ALL).
intervention Names
Drug: Mercaptopurine
Drug: Methotrexate
Drug: Nelarabine
Drug: Prednisone
Drug: Vincristine Sulfate
label
Group I Arm II (Maintenance chemotherapy)
type
ACTIVE_COMPARATOR
description
Patients receive methotrexate IT on days 1, 8, 15, and 22; cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine IV over 15-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO on days 1-14 and 29-42; vincristine sulfate IV on days 15, 22, 43 and 50; and pegaspargase IM or IV over 1-2 hours on days 15 and 43. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 11-12, 15-19, and 22-26. (DS patients excluded as of 09/29/10.) Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT (1,200 cGy/dose) QD on days 15-21 and 22-28. Patients with low-risk disease do not undergo CRT.
intervention Names
Drug: Cyclophosphamide
Drug: Cytarabine
Drug: Leucovorin Calcium
Drug: Mercaptopurine
Drug: Methotrexate
Drug: Pegaspargase
Radiation: Radiation Therapy
Drug: Vincristine Sulfate
label
Group I Arm III (Consolidation chemotherapy)
type
ACTIVE_COMPARATOR
description
Patients receive vincristine sulfate IV on days 1, 8, 15, 43, and 50; dexamethasone IV or PO BID on days 1-21 (for patients \< 10 years of age) OR on days 1-7 and 15-21 (for patients \>= 10 years of age and for patients with DS); doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6, AND day 43; methotrexate IT on days 1, 29, and 36; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV over 15-30 minutes or SC on days 29-32 and 36-39; and thioguanine PO on days 29-42. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose (DS patients excluded as of 09/29/10).
intervention Names
Drug: Cyclophosphamide
Drug: Cytarabine
Drug: Dexamethasone
Drug: Doxorubicin Hydrochloride
Drug: Leucovorin Calcium
Drug: Methotrexate
Drug: Pegaspargase
Drug: Thioguanine
Drug: Vincristine Sulfate
label
Group I Arm III (Delayed intensification chemotherapy)
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Group I Arm II (Interim maintenance chemotherapy)
description
Given IM or IV
name
Asparaginase
other Names
ASP-1
Asparaginase II
Asparaginase-E.Coli
Colaspase
Elspar
Kidrolase
L-Asnase
L-ASP
L-Asparaginase
L-Asparagine Amidohydrolase
Laspar
Lcf-ASP
type
DRUG
arm Group Labels
Group 1 Arm IV (Consolidation chemotherapy)
Group I Arm I (Consolidation chemotherapy)
Group I Arm I (Delayed intensification chemotherapy
Group I Arm II (Consolidation chemotherapy)
Group I Arm II (Delayed intensification chemotherapy)
Group I Arm III (Consolidation chemotherapy)
Group I Arm III (Delayed intensification chemotherapy)
Group I Arm IV (Delayed intensification chemotherapy)
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
Group 0 Induction Therapy
Group 1 Arm IV (Consolidation chemotherapy)
Group I Arm I (Consolidation chemotherapy)
Group I Arm I (Delayed intensification chemotherapy
Group I Arm II (Consolidation chemotherapy)
Group I Arm II (Delayed intensification chemotherapy)
Group I Arm III (Consolidation chemotherapy)
Group I Arm III (Delayed intensification chemotherapy)
Group I Arm IV (Delayed intensification chemotherapy)
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 0 Induction Therapy
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
Group I Arm I (Delayed intensification chemotherapy
Group I Arm II (Delayed intensification chemotherapy)
Group I Arm III (Delayed intensification chemotherapy)
Group I Arm IV (Delayed intensification chemotherapy)
description
Given IV or PO
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
Group I Arm I (Delayed intensification chemotherapy
Group I Arm II (Delayed intensification chemotherapy)
Group I Arm III (Delayed intensification chemotherapy)
Group I Arm IV (Delayed intensification chemotherapy)
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 I Arm I (Maintenance chemotherapy)
Group I Arm III (Interim maintenance chemotherapy)
Group I Arm IV (Interim maintenance chemotherapy)
description
Correlative studies
name
Laboratory Biomarker Analysis
type
OTHER
arm Group Labels
Group I Arm I (Consolidation chemotherapy)
Group I Arm I (Delayed intensification chemotherapy
Group I Arm I (Interim maintenance chemotherapy)
Group I Arm III (Consolidation chemotherapy)
Group I Arm III (Delayed intensification chemotherapy)
Group I Arm III (Interim maintenance chemotherapy)
Group I Arm IV (Interim maintenance chemotherapy)
description
Given PO
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
Group 1 Arm IV (Consolidation chemotherapy)
Group I Arm I (Consolidation chemotherapy)
Group I Arm I (Maintenance chemotherapy)
Group I Arm II (Consolidation chemotherapy)
Group I Arm II (Maintenance chemotherapy)
Group I Arm III (Consolidation chemotherapy)
Group I Arm III (Interim maintenance chemotherapy)
Group I Arm IV (Interim maintenance chemotherapy)
Group I Arm IV (Maintenance chemotherapy)
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
arm Group Labels
Group 0 Induction Therapy
Group 1 Arm IV (Consolidation chemotherapy)
Group I Arm I (Consolidation chemotherapy)
Group I Arm I (Delayed intensification chemotherapy
Group I Arm I (Interim maintenance chemotherapy)
Group I Arm I (Maintenance chemotherapy)
Group I Arm II (Consolidation chemotherapy)
Group I Arm II (Interim maintenance chemotherapy)
Group I Arm II (Maintenance chemotherapy)
Group I Arm III (Consolidation chemotherapy)
Group I Arm III (Delayed intensification chemotherapy)
Group I Arm III (Interim maintenance chemotherapy)
description
Given IT or PO
name
Methotrexate
other Names
Abitrexate
Alpha-Methopterin
Amethopterin
Brimexate
CL 14377
CL-14377
Emtexate
Emthexat
Emthexate
Farmitrexat
Fauldexato
Folex
type
DRUG
arm Group Labels
Group 1 Arm IV (Consolidation chemotherapy)
Group I Arm II (Consolidation chemotherapy)
Group I Arm II (Delayed intensification chemotherapy)
Group I Arm II (Maintenance chemotherapy)
Group I Arm IV (Delayed intensification chemotherapy)
Group I Arm IV (Maintenance chemotherapy)
description
Given IV
name
Nelarabine
other Names
2-Amino-6-methoxypurine arabinoside
506U78
Arranon
Compound 506U78
GW506U78
type
DRUG
arm Group Labels
Group 0 Induction Therapy
Group 1 Arm IV (Consolidation chemotherapy)
Group I Arm I (Consolidation chemotherapy)
Group I Arm I (Delayed intensification chemotherapy
Group I Arm I (Interim maintenance chemotherapy)
Group I Arm II (Consolidation chemotherapy)
Group I Arm II (Delayed intensification chemotherapy)
Group I Arm II (Interim maintenance chemotherapy)
Group I Arm III (Consolidation chemotherapy)
Group I Arm III (Delayed intensification chemotherapy)
Group I Arm IV (Delayed intensification chemotherapy)
description
Given IM or IV
name
Pegaspargase
other Names
L-Asparaginase with Polyethylene Glycol
Oncaspar
Oncaspar-IV
PEG-Asparaginase
PEG-L-Asparaginase
PEG-L-Asparaginase (Enzon - Kyowa Hakko)
PEGLA
Polyethylene Glycol L-Asparaginase
Polyethylene Glycol-L-Asparaginase
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 1895
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Disease Free Probability where 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.
measure
Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV)
time Frame
4 years from randomization at the end of induction
description
Disease Free Probability where 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
measure
Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I + Arm III vs. Arm II + Arm IV)
time Frame
4 years from randomization at the end of induction
description
Disease-free survival defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, remission death) or date of last contact for those who are event-free.
measure
Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV)
time Frame
4 years from randomization at the end of induction
description
Disease Free Probability where 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.
measure
Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I + Arm II vs. Arm III + Arm IV)
time Frame
4 years from randomization at the end of induction
description
Disease Free Probability where 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.
measure
Disease-free Survival (DFS) for T-cell Lymphoblastic Lymphoma (T-LLy) Cohort
time Frame
4 years from end of induction

secondary Outcomes

description
Cumulative incidence of CNS relapse adjusting for DFS events, was calculated using the method Gray et. al. High risk patients receive cranial radiation and low risk patients receive no cranial radiation.
measure
Cumulative Incidence of CNS Relapse for T-ALL by Risk Group
time Frame
4 years from randomization at the end of induction

Full study description

brief Summary: This randomized phase III trial is studying different combination chemotherapy regimens and their side effects and comparing how well they work in treating young patients with newly diagnosed T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma. After a common induction therapy, patients were risk assigned and eligible for one or both post-induction randomizations: Escalating dose Methotrexate versus High Dose Methotrexate in Interim Maintenance therapy, No Nelarabine versus Nelarabine in Consolidation therapy. T-ALL patients are risk assigned as Low Risk, Intermediate Risk or High Risk. Low Risk patients are not eligible for the Nelarabine randomization, Patients with CNS disease at diagnosis were assgined to receive High Dose Methotrexate, patients who failed induction therapy were assigned to receive Nelarabine and High Dose Methotrexate. T-LLy patients were all assigned to escalating dose Methotrexate and were risk assigned as Standard Risk, High Risk and induction failures. Standard risk patients did not receive nelarabine, High risk T-LLy patients were randomized to No Nelarabine versus Nelarabine, and Induction failures were assigned to receive Nelarabine.
detailed Description: PRIMARY OBJECTIVES: I. To determine, through randomization, the relative safety and efficacy of the addition of nelarabine (Compound 506U78) to augmented Berlin-Frankfurt-Münster (BFM) therapy (Regimen C, Children's Cancer Group \[CCG\]-1961). II. To determine the relative safety and efficacy of high dose methotrexate (5 g/m\^2) with leucovorin (leucovorin calcium) rescue compared to escalating methotrexate without leucovorin rescue plus pegaspargase (Capizzi I) delivered during interim maintenance. III. To gain preliminary data on the use of nelarabine in patients with high risk T-cell lymphoblastic lymphoma and its effect on long-term survival. SECONDARY OBJECTIVES: I. To determine the relative safety and efficacy of withholding radiation in patients with low risk T-cell acute lymphoblastic leukemia (T-ALL), while treating Intermediate and high risk patients with 1200 cGy of prophylactic cranial radiation. OUTLINE: This is a randomized, controlled, factorial-group, multicenter study. GROUP 0 (INDUCTION THERAPY): All patients (T-ALL and T-LLy) receive cytarabine intrathecally (IT) on day 1; vincristine sulfate intravenously (IV) on days 1, 8, 15, and 22; prednisone IV or orally (PO) twice daily (BID) on days 1-28; pegaspargase intramuscularly (IM) (may give IV over 1 to 2 hours) on day 4, 5, or 6; duanorubicin IV on days 1, 8, 15 and 22; and methotrexate IT on days 8 and 29 (and days 15 and 22 for patients with CNS3 disease). GROUP I ARM I COMBINATION CHEMOTHERAPY (CONSOLIDATION CHEMOTHERAPY): Patients receive methotrexate IT on days 1, 8, 15, and 22; cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine IV over 15-30 minutes or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO on days 1-14 and 29-42; vincristine sulfate IV on days 15, 22, 43 and 50; and pegaspargase IM or IV over 1-2 hours on days 15 and 43. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 11-12, 15-19, and 22-26. (DS patients excluded as of 09/29/10.) Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT (1,200 cGy/dose) QD on days 15-21 and 22-28. Patients with low-risk disease do not undergo conformal radiation therapy (CRT). Patients with standard risk T-LLy received Arm I, and those with high risk T-LLy were randomized between Arm I and Arm II combination chemotherapy. GROUP I ARM I COMBINATION CHEMOTHERAPY (DELAYED INTENSIFICATION CHEMOTHERAPY): Patients receive vincristine sulfate IV on days 1, 8, 15, 43, and 50; dexamethasone IV or PO BID on days 1-21 (for patients \< 10 years of age) OR on days 1-7 and 15-21 (for patients \>= 10 years of age and for patients with DS); doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6, AND day 43; methotrexate IT on days 1, 29, and 36; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV over 15-30 minutes or SC on days 29-32 and 36-39; and thioguanine PO on days 29-42. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose (DS patients excluded as of 09/29/10). Standard risk T-LLy patients were assigned to Arm I and those with high risk were randomized between Arm I and Arm II. GROUP I ARM I COMBINATION CHEMOTHERAPY (INTERIM MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate IV and escalating doses of methotrexate IV on days 1, 11, 21, 31, and 41; pegaspargase\* IM or IV over 1-2 hours on days 2 and 22; and methotrexate IT on days 1 and 31. Patients with DS also receive leucovorin calcium PO 48 and 60 hours after each methotrexate IT dose (DS patients excluded as of 09/29/10). Note: \*Patients with an allergy to pegaspargase receive Erwinia asparaginase on days 2, 4, 6, 8, 10, 12, 22, 24, 26, 28, 30, and 32. GROUP I ARM I COMBINATION CHEMOTHERAPY (MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate IV on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61; mercaptopurine PO QD on days 1-84; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; and methotrexate IT on day 1. Treatment repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 119) (for girls with T-ALL), all patients with T-LLy, and 3 years from the start of interim maintenance therapy (approximately week 171) (for boys with T-ALL). GROUP I ARM II COMBINATION CHEMOTHERAPY (CONSOLIDATION CHEMOTHERAPY): Patients receive nelarabine IV over 60 minutes on days 1-5 and 43-47; methotrexate IT on days 15, 22, 57, and 64; cyclophosphamide IV over 30 minutes on days 8 and 50; cytarabine IV over 15-30 minutes or SC on days 8-11, 15-18, 50-53 and 57-60; mercaptopurine PO on days 8-21 and 50-63; vincristine sulfate IV on days 22, 29, 64, and 71; and pegaspargase IM or IV over 1-2 hours on days 22 and 64. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 15, 22-26, and 29-33 (DS patients excluded as of 09/29/10). (Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT QD on days 22-28 and 29-35. Patients with high risk T-LLy were either randomized to Arm I or Arm II. Patients with T-LLy who failed induction therapy were assigned to Arm II. GROUP I ARM II COMBINATION CHEMOTHERAPY (DELAYED INTENSIFICATION CHEMOTHERAPY): Patients receive vincristine sulfate IV on days 1, 8, 15, and 50; dexamethasone IV or PO BID on days 1-21 (for patients \< 10 years of age) OR on days 1-7 and 15-21 (for patients \>= 10 years of age); doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6 AND day 50; methotrexate IT on days 1, 36, and 43; nelarabine IV over 60 minutes on days 29-33; cyclophosphamide IV over 30 minutes on day 36; cytarabine IV over 15-30 minutes or SC on days 36-39 and 43-46; and thioguanine PO on days 36-49. GROUP I ARM II COMBINATION CHEMOTHERAPY (INTERIM MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate IV and escalating doses of methotrexate IV on days 1, 11, 21, 31, and 41; pegaspargase\* IM or IV over 1-2 hours on days 2 and 22; and methotrexate IT on days 1 and 31. Note: \*Patients with an allergy to pegaspargase receive Erwinia asparaginase on Monday, Wednesday and Friday for two consecutive weeks starting the day of asparaginase substitution. GROUP I ARM II COMBINATION CHEMOTHERAPY (MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate, prednisone, mercaptopurine, methotrexate PO, methotrexate IT, and nelarabine in Cycles 1, 2 and 3. Patients then receive treatment (without nelarabine) as follows: vincristine sulfate, prednisone, mercaptopurine, methotrexate PO, and methotrexate IT as in arm II. Treatment (without nelarabine) repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 121) (for girls with T-ALL), and for those with T-LLY, and 3 years from the start of interim maintenance therapy (approximately week 173) (for boys with T-ALL). GROUP I ARM III COMBINATION CHEMOTHERAPY (CONSOLIDATION CHEMOTHERAPY): Patients receive methotrexate IT on days 1, 8, 15, and 22; cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine IV over 15-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO on days 1-14 and 29-42; vincristine sulfate IV on days 15, 22, 43 and 50; and pegaspargase IM or IV over 1-2 hours on days 15 and 43. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 11-12, 15-19, and 22-26. (DS patients excluded as of 09/29/10.) Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT (1,200 cGy/dose) QD on days 15-21 and 22-28. Patients with low-risk disease do not undergo CRT. GROUP I ARM III COMBINATION CHEMOTHERAPY (DELAYED INTENSIFICATION CHEMOTHERAPY): Patients receive vincristine sulfate IV on days 1, 8, 15, 43, and 50; dexamethasone IV or PO BID on days 1-21 (for patients \< 10 years of age) OR on days 1-7 and 15-21 (for patients \>= 10 years of age and for patients with DS); doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6, AND day 43; methotrexate IT on days 1, 29, and 36; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV over 15-30 minutes or SC on days 29-32 and 36-39; and thioguanine PO on days 29-42. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose (DS patients excluded as of 09/29/10). GROUP I ARM III COMBINATION CHEMOTHERAPY (INTERIM MAINTENANCE CHEMOTHERAPY): Patients receive high dose methotrexate (HDMTX) IV over 24 hours and vincristine sulfate IV on days 1, 15, 29, and 43; mercaptopurine PO on days 1-56; and methotrexate IT on days 1 and 29. Beginning 42 hours after the start of HDMTX, patients also receive leucovorin calcium IV or PO once every 6 hours for 3 doses. GROUP I ARM III COMBINATION CHEMOTHERAPY (MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate IV on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61; mercaptopurine PO QD on days 1-84; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; and methotrexate IT on day 1. Treatment repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 119) (for girls with T-ALL) and all patients with T-LLy, and 3 years from the start of interim maintenance therapy (approximately week 171) (for boys with T-ALL). GROUP I ARM IV COMBINATION CHEMOTHERAPY (CONSOLIDATION CHEMOTHERAPY): Patients receive nelarabine IV over 60 minutes on days 1-5 and 43-47; methotrexate IT on days 15, 22, 57, and 64; cyclophosphamide IV over 30 minutes on days 8 and 50; cytarabine IV over 15-30 minutes or SC on days 8-11, 15-18, 50-53 and 57-60; mercaptopurine PO on days 8-21 and 50-63; vincristine sulfate IV on days 22, 29, 64, and 71; and pegaspargase IM or IV over 1-2 hours on days 22 and 64. (DS patients excluded as of 09/29/10). (Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT QD on days 22-28 and 29-35. GROUP I ARM IV COMBINATION CHEMOTHERAPY (DELAYED INTENSIFICATION CHEMOTHERAPY): Patients receive vincristine sulfate IV on days 1, 8, 15, and 50; dexamethasone IV or PO BID on days 1-21 (for patients \< 10 years of age) OR on days 1-7 and 15-21 (for patients \>= 10 years of age); doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6 AND day 50; methotrexate IT on days 1, 36, and 43; nelarabine IV over 60 minutes on days 29-33; cyclophosphamide IV over 30 minutes on day 36; cytarabine IV over 15-30 minutes or SC on days 36-39 and 43-46; and thioguanine PO on days 36-49. GROUP I ARM IV COMBINATION CHEMOTHERAPY (INTERIM MAINTENANCE CHEMOTHERAPY): Patients receive HDMTX IV over 24 hours and vincristine sulfate IV on days 1, 15, 29, and 43; mercaptopurine PO on days 1-56; and methotrexate IT on days 1 and 29. Beginning 42 hours after the start of HDMTX, patients also receive leucovorin calcium IV or PO once every 6 hours for 3 doses. GROUP I ARM IV COMBINATION CHEMOTHERAPY (MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate, prednisone, mercaptopurine, methotrexate PO, methotrexate IT, and nelarabine in Cycles 1, 2 and 3. Patients then receive treatment (without nelarabine) as follows: vincristine sulfate, prednisone, mercaptopurine, methotrexate PO, and methotrexate IT as in arm II. Treatment (without nelarabine) repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 121) (for girls with T-ALL), and for those with T-LLY, and 3 years from the start of interim maintenance therapy (approximately week 173) (for boys with T-ALL). After completion of study therapy, patients are followed periodically for at least 10 years.

Source references

references

citation
Orgel E, Maese LD, Devidas M, Militano O, Rau RE, Angiolillo AL, McNeer JL, Schore RJ, Borowitz MJ, Wood B, Raetz EA, Silverman LB, Winick NJ, Larsen EC, Carroll WL, Winter SS, Dunsmore KP, Hunger SP, Loh ML. Toxicity from asparaginase during acute lymphoblastic leukemia induction: a report from the Children's Oncology Group. Blood Adv. 2026 Jul 28;10(14):4923-4930. doi: 10.1182/bloodadvances.2026019870.
pmid
42085640
type
DERIVED
citation
Pinton A, Courtois L, Delafoy M, Bonnet M, Cieslak A, Lhermitte L, Simonin M, Dourthe ME, Touzart A, Andrieu GP, Dombret H, Baruchel A, Spicuglia S, Payet-Bornet D, Boissel N, Macintyre E, Asnafi V. Homeodomain-driven oncogenic diversion to a gammadeltaTCR phenotype in T-cell acute lymphoblastic leukemia. Blood. 2026 Jun 4;147(23):2793-2808. doi: 10.1182/blood.2025030626.
pmid
41592282
type
DERIVED
citation
Xu J, Teachey DT. Genomic Classification of T-Cell Acute Lymphoblastic Leukemia: Current Paradigms and Future Biomarkers. J Natl Compr Canc Netw. 2025 Jun 18;23(7):e257028. doi: 10.6004/jnccn.2025.7028.
pmid
40533067
type
DERIVED
citation
Wood BL, Devidas M, Summers RJ, Chen Z, Asselin B, Rabin KR, Zweidler-McKay PA, Winick NJ, Borowitz MJ, Carroll WL, Raetz EA, Loh ML, Hunger SP, Dunsmore KP, Teachey DT, Winter SS. Prognostic significance of ETP phenotype and minimal residual disease in T-ALL: a Children's Oncology Group study. Blood. 2023 Dec 14;142(24):2069-2078. doi: 10.1182/blood.2023020678.
pmid
37556734
type
DERIVED
citation
Gossai NP, Devidas M, Chen Z, Wood BL, Zweidler-McKay PA, Rabin KR, Loh ML, Raetz EA, Winick NJ, Burke MJ, Carroll AJ, Esiashvili N, Heerema NA, Carroll WL, Hunger SP, Dunsmore KP, Winter SS, Teachey DT. Central nervous system status is prognostic in T-cell acute lymphoblastic leukemia: a Children's Oncology Group report. Blood. 2023 Apr 13;141(15):1802-1811. doi: 10.1182/blood.2022018653.
pmid
36603187
type
DERIVED
citation
Gaynon PS, Parekh C. A new standard of care for childhood T-cell acute lymphoblastic leukemia? Pediatr Blood Cancer. 2021 Oct;68(10):e29238. doi: 10.1002/pbc.29238. Epub 2021 Jul 24. No abstract available.
pmid
34302711
type
DERIVED
citation
Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Oct 1;38(28):3282-3293. doi: 10.1200/JCO.20.00256. Epub 2020 Aug 19.
pmid
32813610
type
DERIVED
citation
Hayashi RJ, Winter SS, Dunsmore KP, Devidas M, Chen Z, Wood BL, Hermiston ML, Teachey DT, Perkins SL, Miles RR, Raetz EA, Loh ML, Winick NJ, Carroll WL, Hunger SP, Lim MS, Gross TG, Bollard CM. Successful Outcomes of Newly Diagnosed T Lymphoblastic Lymphoma: Results From Children's Oncology Group AALL0434. J Clin Oncol. 2020 Sep 10;38(26):3062-3070. doi: 10.1200/JCO.20.00531. Epub 2020 Jun 17.
pmid
32552472
type
DERIVED
citation
Winter SS, Dunsmore KP, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Gaynon PS, Borowitz MJ, Loh ML, Rabin KR, Raetz EA, Zweidler-Mckay PA, Winick NJ, Carroll WL, Hunger SP. Improved Survival for Children and Young Adults With T-Lineage Acute Lymphoblastic Leukemia: Results From the Children's Oncology Group AALL0434 Methotrexate Randomization. J Clin Oncol. 2018 Oct 10;36(29):2926-2934. doi: 10.1200/JCO.2018.77.7250. Epub 2018 Aug 23.
pmid
30138085
type
DERIVED