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Combination Chemotherapy With or Without Bortezomib in Treating Younger Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or Stage II-IV T-Cell Lymphoblastic Lymphoma

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Active, not recruiting
CT.gov ID
NCT02112916
Collaborator
(none)
847
Enrollment
212
Locations
2
Arms
159
Anticipated Duration (Months)
4
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This randomized phase III trial compares how well combination chemotherapy works when given with or without bortezomib in treating patients with newly diagnosed T-cell acute lymphoblastic leukemia or stage II-IV T-cell lymphoblastic lymphoma. Bortezomib may help reduce the number of leukemia or lymphoma cells by blocking some of the enzymes needed for cell growth. It may also help chemotherapy work better by making cancer cells more sensitive to the drugs. It is not yet known if giving standard chemotherapy with or without bortezomib is more effective in treating newly diagnosed T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

PRIMARY OBJECTIVES:
  1. To compare event-free survival (EFS) in patients with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LLy) who are randomized to a modified augmented Berlin-Frankfurt-Munster (ABFM) backbone versus bortezomib plus the modified ABFM backbone.
SECONDARY OBJECTIVES:

  1. To determine the safety and feasibility of modifying standard therapy for T-ALL and T-LLy based on the results of UKALL 2003, which includes a dexamethasone-based induction, additional doses of pegaspargase (PEG-ASP) during induction and delayed intensification (DI), and dexamethasone pulses during maintenance therapy.

  2. To determine if prophylactic (presymptomatic) cranial radiation therapy (CRT) can be safely and effectively eliminated in the 85-90% of T-ALL patients classified as standard or intermediate risk.

  3. To determine the proportion of end of consolidation (EOC) minimal residual disease (MRD)

= 0.1% T-ALL patients who become MRD negative (undetectable by flow cytometry) after intensification of chemotherapy, using three high risk (HR) BFM blocks, and to compare EFS between the patients who become MRD negative after the three HR BFM blocks and continue on chemotherapy with those who continue to have detectable MRD and are eligible for other treatment strategies, including hematopoietic stem cell transplant (HSCT).

  1. To compare the EFS between very high risk (induction failure) T-LLy patients treated with HR BFM intensification blocks who have partial or complete response (PR or CR) with those who do not respond (NR).
CORRELATIVE OBJECTIVES:

  1. To investigate the prognostic significance of day 29 bone marrow (BM) MRD in T-LLy patients.

  2. To determine if protein expression patterns can predict bortezomib response and drug resistance in T-ALL.

  3. To analyze and target relevant signaling pathways in T-ALL blasts, focusing on early T cell precursor (ETP) acute lymphoblastic leukemia (ALL).

OUTLINE: Patients are randomized to 1 of 2 treatment arms. Patients are risk assigned based on data from end of induction and/or consolidation therapy; this then modifies the subsequent therapy received.

T-ALL Risk Group Definitions:

Standard Risk (SR): CNS1*, lumbar puncture prior to steroid therapy (not steroid pretreated), Day 29 (end of induction) bone marrow M1, Day 29 bone marrow minimal residual disease (MRD) <=0.01%, no testicular leukemia at diagnosis

Intermediate Risk (IR): Not SR or VHR

Very High Risk (VHR): M3 marrow at Day 29 and/or end of consolidation (EOC) MRD >=0.1%

*CNS2 and CNS3 cannot be SR and are assigned to IR or VHR based on marrow response.

T-LL Risk Group Definitions:

Standard Risk (SR): CNS1*, MRD at diagnosis <1% in bone marrow, lumbar puncture prior to steroid therapy (not steroid pretreated), Day 29 (end of induction) complete response (CR) or partial response (PR)

Intermediate Risk (IR): Not SR or VHR

Very High Risk (VHR): Stable Disease (SD)/No response (NR) at Day 29 (End of Induction)

*CNS2 and CNS3 cannot be SR and are assigned to IR or VHR based on radiographic response

ARM A INDUCTION: Patients receive cytarabine intrathecally (IT) at time of diagnostic lumbar puncture (if within 72 hours from start of protocol therapy) OR day 1; vincristine sulfate intravenously (IV) over 1 minute on days 1, 8, 15, and 22; dexamethasone orally (PO) twice daily (BID) on days 1-28 (no taper); daunorubicin hydrochloride IV over 1-15 minutes on days 1, 8, 15, and 22; pegaspargase IV over 1-2 hours on days 4 and 18; and methotrexate IT on days 8 and 29 (and on days 15 and 22 for central nervous system 3 involvement [CNS3] T-ALL patients).

ARM A CONSOLIDATION: Beginning on day 36 from Induction, patients receive methotrexate IT on days 1, 8, 15, and 22 (days 1 and 8 only for CNS3 T-ALL or CNS3 T-LLy patients); 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; pegaspargase IV over 1-2 hours on days 15 and 43; and vincristine sulfate IV on days 15, 22, 43, and 50. Patients with persistent testicular disease undergo radiation therapy.

Patients are then assigned to subsequent therapy according to risk assignment. Patients with standard risk (SR) disease receive Interim Maintenance with Capizzi methotrexate (CMTX); patients with intermediate risk (IR) disease receive Interim Maintenance with high-dose methotrexate (HDMTX), Delayed Intensification, and then Interim Maintenance with CMTX; and patients with very high risk (VHR) disease receive 3 HR Intensification Blocks, Delayed Intensification, and then Interim Maintenance with CMTX.

ARM A CMTX INTERIM MAINTENANCE: Patients receive vincristine sulfate IV over 1 minute on 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; pegaspargase IV over 1-2 hours on days 2 and 22; and methotrexate IT on days 1 and 31. The next course (based on risk assignment) begins on day 57 or when blood counts recover (whichever occurs later).

ARM A DELAYED INTENSIFICATION: 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 15 minutes on days, 1, 8, and 15; pegaspargase IV over 1-2 hours on days 4, 18, and 43; methotrexate IT on days 1, 29, and 36; 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 on days 29-42. The next course (based on risk assignment) begins on day 64 or when blood counts recover (whichever occurs later).

ARM A HDMTX INTERIM MAINTENANCE: Patients receive high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium IV or PO on days 3-4, 17-18, 31-32, and 45-46; vincristine sulfate IV on days 1, 15, 29, and 43; mercaptopurine PO QD on days 1-56; and methotrexate IT on days 1 and 29. The next course (based on randomization assignment) begins on day 57 or when blood counts recover (whichever occurs later).

ARM A INTENSIFICATION BLOCK I: Patients receive dexamethasone IV or PO BID on days 1-5; high-dose methotrexate IV over 24 hours on day 1; leucovorin calcium IV or PO on days 3-4; vincristine sulfate IV on days 1 and 6; cyclophosphamide IV over 1-6 hours on days 2-4; high-dose cytarabine IV over 3 hours every 12 hours on day 5; pegaspargase IV over 1-2 hours on day 6; and triple IT therapy comprising methotrexate IT, hydrocortisone IT, and cytarabine IT on day 1. The next course (Intensification Block II) begins on day 22 or when blood counts recover (whichever occurs later).

ARM A INTENSIFICATION BLOCK II: Patients receive dexamethasone PO BID or IV on days 1-5; high-dose methotrexate IV over 24 hours on day 1; leucovorin calcium PO or IV on days 3-4; vincristine sulfate IV on days 1 and 6; ifosfamide IV over 1 hour every 12 hours on days 2-4; daunorubicin hydrochloride IV over 30 minutes on day 5; pegaspargase IV over 1-2 hours on day 6; and triple IT therapy on day 1 as in Intensification Block I. The next course (Intensification Block III) begins on day 22 or when blood counts recover (whichever occurs later).

ARM A INTENSIFICATION BLOCK III: Patients receive dexamethasone PO BID or IV on days 1-5; high-dose cytarabine IV over 3 hours every 12 hours on days 1-2; etoposide IV over 1-2 hours every 12 hours on days 3-5; pegaspargase IV over 1-2 hours on day 6; and triple IT therapy on day 5 as in Intensification Block I. The next course (based on randomization) begins on day 22 or when blood counts recover (whichever occurs later).

ARM A MAINTENANCE THERAPY: All patients receive vincristine sulfate IV over 1 minute on days 1, 29, and 57; dexamethasone PO BID or IV on days 1-5, 29-33, and 57-61; mercaptopurine PO on days 1-84; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (omit day 29 for SR patients during the first 4 cycles); methotrexate IT on day 1 (and day 29 during the first 4 cycles for SR patients and during the first 2 cycles for IR patients). Patients with CNS1-3VHR and CNS2 VHR, and CNS3 IR disease also undergo cranial radiation therapy during the first 4 weeks (cycle 1). Treatment in female patients with T-ALL and patients with T-LLY repeats every 12 weeks for up to 2 years from the start of Interim Maintenance (week 119). Treatment in male patients with T-ALL repeats every 12 weeks for up to 3 years from the start of Interim Maintenance (week 171).

ARM B INDUCTION: Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11(1.3 mg/m^2 per dose); and cytarabine, vincristine sulfate, dexamethasone, daunorubicin hydrochloride, pegaspargase, and methotrexate as in Induction Arm A.

ARM B CONSOLIDATION: Beginning on day 36 from Induction, patients receive methotrexate IT on days 1, 8, 15, and 22 (days 1 and 8 only for CNS3 T-ALL or CNS3 T-LLy patients); 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; pegaspargase IV over 1-2 hours on days 15 and 43; and vincristine sulfate IV on days 15, 22, 43, and 50. Patients with persistent testicular disease undergo radiation therapy.

Patients are then assigned to subsequent therapy according to risk assignment. Patients with standard risk (SR) disease receive Interim Maintenance with Capizzi methotrexate (CMTX); patients with intermediate risk (IR) disease receive Interim Maintenance with high-dose methotrexate (HDMTX), Delayed Intensification, and then Interim Maintenance with CMTX; and patients with very high risk (VHR) disease receive 3 HR Intensification Blocks, Delayed Intensification, and then Interim Maintenance with CMTX.

ARM B CMTX INTERIM MAINTENANCE: Patients receive vincristine sulfate IV over 1 minute on 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; pegaspargase IV over 1-2 hours on days 2 and 22; and methotrexate IT on days 1 and 31. The next course (based on risk assignment) begins on day 57 or when blood counts recover (whichever occurs later).

ARM B DELAYED INTENSIFICATION: Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 15, and 18 (1.3 mg/m^2 per dose); and vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, methotrexate, cyclophosphamide, cytarabine, and thioguanine as in Delayed Intensification Arm A. The next course (based on risk assignment) begins on day 64 or when blood counts recover (whichever occurs later).

ARM B HDMTX INTERIM MAINTENANCE: Patients receive high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium IV or PO on days 3-4, 17-18, 31-32, and 45-46; vincristine sulfate IV on days 1, 15, 29, and 43; mercaptopurine PO QD on days 1-56; and methotrexate IT on days 1 and 29. The next course (based on randomization assignment) begins on day 57 or when blood counts recover (whichever occurs later).

ARM B INTENSIFICATION BLOCK I: Patients receive dexamethasone IV or PO BID on days 1-5; high-dose methotrexate IV over 24 hours on day 1; leucovorin calcium IV or PO on days 3-4; vincristine sulfate IV on days 1 and 6; cyclophosphamide IV over 1-6 hours on days 2-4; high-dose cytarabine IV over 3 hours every 12 hours on day 5; pegaspargase IV over 1-2 hours on day 6; and triple IT therapy comprising methotrexate IT, hydrocortisone IT, and cytarabine IT on day 1. The next course (Intensification Block II) begins on day 22 or when blood counts recover (whichever occurs later).

ARM B INTENSIFICATION BLOCK II: Patients receive dexamethasone PO BID or IV on days 1-5; high-dose methotrexate IV over 24 hours on day 1; leucovorin calcium PO or IV on days 3-4; vincristine sulfate IV on days 1 and 6; ifosfamide IV over 1 hour every 12 hours on days 2-4; daunorubicin hydrochloride IV over 30 minutes on day 5; pegaspargase IV over 1-2 hours on day 6; and triple IT therapy on day 1 as in Intensification Block I. The next course (Intensification Block III) begins on day 22 or when blood counts recover (whichever occurs later).

ARM B INTENSIFICATION BLOCK III: Patients receive dexamethasone PO BID or IV on days 1-5; high-dose cytarabine IV over 3 hours every 12 hours on days 1-2; etoposide IV over 1-2 hours every 12 hours on days 3-5; pegaspargase IV over 1-2 hours on day 6; and triple IT therapy on day 5 as in Intensification Block I. The next course (based on randomization) begins on day 22 or when blood counts recover (whichever occurs later).

ARM B MAINTENANCE THERAPY: All patients receive vincristine sulfate IV over 1 minute on days 1, 29, and 57; dexamethasone PO BID or IV on days 1-5, 29-33, and 57-61; mercaptopurine PO on days 1-84; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (omit day 29 for SR patients during the first 4 cycles); methotrexate IT on day 1 (and day 29 during the first 4 cycles for SR patients and during the first 2 cycles for IR patients). Patients with CNS1-3VHR and CNS2 VHR, and CNS3 IR disease also undergo cranial radiation therapy during the first 4 weeks (cycle 1). Treatment in female patients with T-ALL and patients with T-LLY repeats every 12 weeks for up to 2 years from the start of Interim Maintenance (week 119). Treatment in male patients with T-ALL repeats every 12 weeks for up to 3 years from the start of Interim Maintenance (week 171).

All treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for up to 10 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
847 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase III Randomized Trial Investigating Bortezomib (NSC# 681239) on a Modified Augmented BFM (ABFM) Backbone in Newly Diagnosed T-Lymphoblastic Leukemia (T-ALL) and T-Lymphoblastic Lymphoma (T-LLy)
Actual Study Start Date :
Sep 30, 2014
Actual Primary Completion Date :
Mar 31, 2020
Anticipated Study Completion Date :
Dec 31, 2027

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Arm A (combination chemotherapy)

Patients receive combination chemotherapy without bortezomib. See Detailed Description.

Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamide Monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719

    • Drug: Cytarabine
    Given IT, IV, or SC
    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
  • Arabinofuranosylcytosine
  • Arabinosylcytosine
  • Aracytidine
  • Aracytin
  • Aracytine
  • Beta-Cytosine Arabinoside
  • CHX-3311
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosine Arabinoside
  • Cytosine-.beta.-arabinoside
  • Cytosine-beta-arabinoside
  • Erpalfa
  • Starasid
  • Tarabine PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453

    • Drug: Daunorubicin
    Given IV
    Other Names:
  • Daunomycin
  • Daunorrubicina
  • DNR
  • Leukaemomycin C
  • Rubidomycin
  • Rubomycin C

    • Drug: Daunorubicin Hydrochloride
    Given IV
    Other Names:
  • Cerubidin
  • Cerubidine
  • Cloridrato de Daunorubicina
  • Daunoblastin
  • Daunoblastina
  • Daunoblastine
  • Daunomycin Hydrochloride
  • Daunomycin, hydrochloride
  • Daunorubicin.HCl
  • Daunorubicini Hydrochloridum
  • FI-6339
  • Ondena
  • RP-13057
  • Rubidomycin Hydrochloride
  • Rubilem

    • Drug: Dexamethasone
    Given PO or IV
    Other Names:
  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycadron
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • Decadron
  • Decadron DP
  • Decalix
  • Decameth
  • Decasone R.p.
  • Dectancyl
  • Dekacort
  • Deltafluorene
  • Deronil
  • Desamethasone
  • Desameton
  • Dexa-Mamallet
  • Dexa-Rhinosan
  • Dexa-Scheroson
  • Dexa-sine
  • Dexacortal
  • Dexacortin
  • Dexafarma
  • Dexafluorene
  • Dexalocal
  • Dexamecortin
  • Dexameth
  • Dexamethasone Intensol
  • Dexamethasonum
  • Dexamonozon
  • Dexapos
  • Dexinoral
  • Dexone
  • Dinormon
  • Dxevo
  • Fluorodelta
  • Fortecortin
  • Gammacorten
  • Hexadecadrol
  • Hexadrol
  • Lokalison-F
  • Loverine
  • Methylfluorprednisolone
  • Millicorten
  • Mymethasone
  • Orgadrone
  • Spersadex
  • TaperDex
  • Visumetazone
  • ZoDex

    • Drug: Doxorubicin
    Given IV
    Other Names:
  • Adriablastin
  • Hydroxydaunomycin
  • Hydroxyl Daunorubicin
  • Hydroxyldaunorubicin

    • Drug: Doxorubicin Hydrochloride
    Given IV
    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
  • Chloridrato de Doxorrubicina
  • DOX
  • DOXO-CELL
  • Doxolem
  • Doxorubicin HCl
  • Doxorubicin.HCl
  • Doxorubin
  • Farmiblastina
  • FI 106
  • FI-106
  • hydroxydaunorubicin
  • Rubex

    • Drug: Etoposide
    Given IV
    Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16
  • VP 16-213
  • VP-16
  • VP-16-213
  • VP16

    • Drug: Hydrocortisone Sodium Succinate
    Given IT
    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
  • Hydrocort
  • Hydrocortisone 21-Sodium Succinate
  • Hydrocortisone Na Succinate
  • Kinogen
  • Nordicort
  • Nositrol
  • Sinsurrene
  • Sodium hydrocortisone succinate
  • Solu-Cortef
  • Solu-Glyc

    • Drug: Ifosfamide
    Given IV
    Other Names:
  • Asta Z 4942
  • Asta Z-4942
  • Cyfos
  • Holoxan
  • Holoxane
  • Ifex
  • IFO
  • IFO-Cell
  • Ifolem
  • Ifomida
  • Ifomide
  • Ifosfamidum
  • Ifoxan
  • IFX
  • Iphosphamid
  • Iphosphamide
  • Iso-Endoxan
  • Isoendoxan
  • Isophosphamide
  • Mitoxana
  • MJF 9325
  • MJF-9325
  • Naxamide
  • Seromida
  • Tronoxal
  • Z 4942
  • Z-4942

    • Drug: Leucovorin Calcium
    Given PO or IV
    Other Names:
  • Adinepar
  • Calcifolin
  • Calcium (6S)-Folinate
  • Calcium Folinate
  • Calcium Leucovorin
  • Calfolex
  • Calinat
  • Cehafolin
  • Citofolin
  • Citrec
  • Citrovorum Factor
  • Cromatonbic Folinico
  • Dalisol
  • Disintox
  • Divical
  • Ecofol
  • Emovis
  • Factor, Citrovorum
  • Flynoken A
  • Folaren
  • Folaxin
  • FOLI-cell
  • Foliben
  • Folidan
  • Folidar
  • Folinac
  • Folinate Calcium
  • folinic acid
  • Folinic Acid Calcium Salt Pentahydrate
  • Folinoral
  • Folinvit
  • Foliplus
  • Folix
  • Imo
  • Lederfolat
  • Lederfolin
  • Leucosar
  • leucovorin
  • Rescufolin
  • Rescuvolin
  • Tonofolin
  • Wellcovorin

    • Drug: Mercaptopurine
    Give PO
    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
  • Alti-Mercaptopurine
  • Azathiopurine
  • Bw 57-323H
  • Flocofil
  • Ismipur
  • Leukerin
  • Leupurin
  • Mercaleukim
  • Mercaleukin
  • Mercaptina
  • Mercaptopurinum
  • Mercapurin
  • Mern
  • NCI-C04886
  • Puri-Nethol
  • Purimethol
  • Purine, 6-mercapto-
  • Purine-6-thiol (8CI)
  • Purine-6-thiol, monohydrate
  • Purinethiol
  • Purinethol
  • U-4748
  • WR-2785

    • Drug: Methotrexate
    Given IT, IV, or PO
    Other Names:
  • Abitrexate
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate
  • Mexate-AQ
  • MTX
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039

    • Drug: Pegaspargase
    Given IV
    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

    • Radiation: Radiation Therapy
    Undergo radiation therapy
    Other Names:
  • Cancer Radiotherapy
  • ENERGY_TYPE
  • Irradiate
  • Irradiated
  • Irradiation
  • Radiation
  • Radiation Therapy, NOS
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation

    • Drug: Thioguanine
    Given PO
    Other Names:
  • 2-Amino 6MP
  • 2-Amino-1,7-dihydro-6H-purine-6-thione
  • 2-Amino-6-mercaptopurine
  • 2-Amino-6-purinethiol
  • 2-Aminopurin-6-thiol
  • 2-Aminopurine-6(1H)-thione
  • 2-Aminopurine-6-thiol
  • 2-Aminopurine-6-thiol Hemihydrate
  • 2-Mercapto-6-aminopurine
  • 6-Amino-2-mercaptopurine
  • 6-Mercapto-2-aminopurine
  • 6-Mercaptoguanine
  • 6-TG
  • 6H-Purine-6-thione, 2-amino-1,7-dihydro- (9CI)
  • BW 5071
  • Lanvis
  • Tabloid
  • Thioguanine Hemihydrate
  • Thioguanine Hydrate
  • Tioguanin
  • Tioguanine
  • Wellcome U3B
  • WR-1141
  • X 27

    • Drug: Vincristine
    Given IV
    Other Names:
  • Leurocristine
  • VCR
  • Vincrystine

    • Drug: Vincristine Sulfate
    Given IV
    Other Names:
  • Kyocristine
  • Leurocristine Sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate

    		•
    Experimental: Arm B (combination chemotherapy, bortezomib)

    Patients receive combination chemotherapy with bortezomib (4 doses at 1.3mg/m2 during Induction and 4 doses at 1.3mg/m2 during Delayed Intensification). See Detailed Description.

    Drug: Bortezomib
    Given IV
    Other Names:
  • [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid
  • LDP 341
  • MLN341
  • PS-341
  • PS341
  • Velcade

    • Drug: Cyclophosphamide
    Given IV
    Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamide Monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719

    • Drug: Cytarabine
    Given IT, IV, or SC
    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
  • Arabinofuranosylcytosine
  • Arabinosylcytosine
  • Aracytidine
  • Aracytin
  • Aracytine
  • Beta-Cytosine Arabinoside
  • CHX-3311
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosine Arabinoside
  • Cytosine-.beta.-arabinoside
  • Cytosine-beta-arabinoside
  • Erpalfa
  • Starasid
  • Tarabine PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453

    • Drug: Daunorubicin
    Given IV
    Other Names:
  • Daunomycin
  • Daunorrubicina
  • DNR
  • Leukaemomycin C
  • Rubidomycin
  • Rubomycin C

    • Drug: Daunorubicin Hydrochloride
    Given IV
    Other Names:
  • Cerubidin
  • Cerubidine
  • Cloridrato de Daunorubicina
  • Daunoblastin
  • Daunoblastina
  • Daunoblastine
  • Daunomycin Hydrochloride
  • Daunomycin, hydrochloride
  • Daunorubicin.HCl
  • Daunorubicini Hydrochloridum
  • FI-6339
  • Ondena
  • RP-13057
  • Rubidomycin Hydrochloride
  • Rubilem

    • Drug: Dexamethasone
    Given PO or IV
    Other Names:
  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycadron
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • Decadron
  • Decadron DP
  • Decalix
  • Decameth
  • Decasone R.p.
  • Dectancyl
  • Dekacort
  • Deltafluorene
  • Deronil
  • Desamethasone
  • Desameton
  • Dexa-Mamallet
  • Dexa-Rhinosan
  • Dexa-Scheroson
  • Dexa-sine
  • Dexacortal
  • Dexacortin
  • Dexafarma
  • Dexafluorene
  • Dexalocal
  • Dexamecortin
  • Dexameth
  • Dexamethasone Intensol
  • Dexamethasonum
  • Dexamonozon
  • Dexapos
  • Dexinoral
  • Dexone
  • Dinormon
  • Dxevo
  • Fluorodelta
  • Fortecortin
  • Gammacorten
  • Hexadecadrol
  • Hexadrol
  • Lokalison-F
  • Loverine
  • Methylfluorprednisolone
  • Millicorten
  • Mymethasone
  • Orgadrone
  • Spersadex
  • TaperDex
  • Visumetazone
  • ZoDex

    • Drug: Doxorubicin
    Given IV
    Other Names:
  • Adriablastin
  • Hydroxydaunomycin
  • Hydroxyl Daunorubicin
  • Hydroxyldaunorubicin

    • Drug: Doxorubicin Hydrochloride
    Given IV
    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
  • Chloridrato de Doxorrubicina
  • DOX
  • DOXO-CELL
  • Doxolem
  • Doxorubicin HCl
  • Doxorubicin.HCl
  • Doxorubin
  • Farmiblastina
  • FI 106
  • FI-106
  • hydroxydaunorubicin
  • Rubex

    • Drug: Etoposide
    Given IV
    Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16
  • VP 16-213
  • VP-16
  • VP-16-213
  • VP16

    • Drug: Hydrocortisone Sodium Succinate
    Given IT
    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
  • Hydrocort
  • Hydrocortisone 21-Sodium Succinate
  • Hydrocortisone Na Succinate
  • Kinogen
  • Nordicort
  • Nositrol
  • Sinsurrene
  • Sodium hydrocortisone succinate
  • Solu-Cortef
  • Solu-Glyc

    • Drug: Ifosfamide
    Given IV
    Other Names:
  • Asta Z 4942
  • Asta Z-4942
  • Cyfos
  • Holoxan
  • Holoxane
  • Ifex
  • IFO
  • IFO-Cell
  • Ifolem
  • Ifomida
  • Ifomide
  • Ifosfamidum
  • Ifoxan
  • IFX
  • Iphosphamid
  • Iphosphamide
  • Iso-Endoxan
  • Isoendoxan
  • Isophosphamide
  • Mitoxana
  • MJF 9325
  • MJF-9325
  • Naxamide
  • Seromida
  • Tronoxal
  • Z 4942
  • Z-4942

    • Drug: Leucovorin Calcium
    Given PO or IV
    Other Names:
  • Adinepar
  • Calcifolin
  • Calcium (6S)-Folinate
  • Calcium Folinate
  • Calcium Leucovorin
  • Calfolex
  • Calinat
  • Cehafolin
  • Citofolin
  • Citrec
  • Citrovorum Factor
  • Cromatonbic Folinico
  • Dalisol
  • Disintox
  • Divical
  • Ecofol
  • Emovis
  • Factor, Citrovorum
  • Flynoken A
  • Folaren
  • Folaxin
  • FOLI-cell
  • Foliben
  • Folidan
  • Folidar
  • Folinac
  • Folinate Calcium
  • folinic acid
  • Folinic Acid Calcium Salt Pentahydrate
  • Folinoral
  • Folinvit
  • Foliplus
  • Folix
  • Imo
  • Lederfolat
  • Lederfolin
  • Leucosar
  • leucovorin
  • Rescufolin
  • Rescuvolin
  • Tonofolin
  • Wellcovorin

    • Drug: Mercaptopurine
    Give PO
    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
  • Alti-Mercaptopurine
  • Azathiopurine
  • Bw 57-323H
  • Flocofil
  • Ismipur
  • Leukerin
  • Leupurin
  • Mercaleukim
  • Mercaleukin
  • Mercaptina
  • Mercaptopurinum
  • Mercapurin
  • Mern
  • NCI-C04886
  • Puri-Nethol
  • Purimethol
  • Purine, 6-mercapto-
  • Purine-6-thiol (8CI)
  • Purine-6-thiol, monohydrate
  • Purinethiol
  • Purinethol
  • U-4748
  • WR-2785

    • Drug: Methotrexate
    Given IT, IV, or PO
    Other Names:
  • Abitrexate
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate
  • Mexate-AQ
  • MTX
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039

    • Drug: Pegaspargase
    Given IV
    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

    • Radiation: Radiation Therapy
    Undergo radiation therapy
    Other Names:
  • Cancer Radiotherapy
  • ENERGY_TYPE
  • Irradiate
  • Irradiated
  • Irradiation
  • Radiation
  • Radiation Therapy, NOS
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation

    • Drug: Thioguanine
    Given PO
    Other Names:
  • 2-Amino 6MP
  • 2-Amino-1,7-dihydro-6H-purine-6-thione
  • 2-Amino-6-mercaptopurine
  • 2-Amino-6-purinethiol
  • 2-Aminopurin-6-thiol
  • 2-Aminopurine-6(1H)-thione
  • 2-Aminopurine-6-thiol
  • 2-Aminopurine-6-thiol Hemihydrate
  • 2-Mercapto-6-aminopurine
  • 6-Amino-2-mercaptopurine
  • 6-Mercapto-2-aminopurine
  • 6-Mercaptoguanine
  • 6-TG
  • 6H-Purine-6-thione, 2-amino-1,7-dihydro- (9CI)
  • BW 5071
  • Lanvis
  • Tabloid
  • Thioguanine Hemihydrate
  • Thioguanine Hydrate
  • Tioguanin
  • Tioguanine
  • Wellcome U3B
  • WR-1141
  • X 27

    • Drug: Vincristine
    Given IV
    Other Names:
  • Leurocristine
  • VCR
  • Vincrystine

    • Drug: Vincristine Sulfate
    Given IV
    Other Names:
  • Kyocristine
  • Leurocristine Sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Event-free Survival (EFS) for Modified Augmented Berlin-Frankfurt-Munster Backbone With or Without Bortezomib in All Randomized Patients [3 years]

      EFS is calculated as time from randomization at study entry to first event (induction failure, induction death, relapse, second malignancy, remission death) or date of last contact. Three-year EFS rates will be calculated for both groups.

    Secondary Outcome Measures

    1. Toxicity Rates Associated With Modified Standard Therapy, Including Dexamethasone and Additional Pegaspargase [3 years from start of therapy by patient]

      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 4.0

    2. EFS for Standard (SR) and Intermediate Risk (IR) T-ALL Patients on the Non-bortezomib Containing Arm on This Study (no Cranial Radiation Therapy [CRT]) and Similar Patients on AALL0434 (Received CRT) [3 years]

      EFS is calculated as time from randomization at study entry to first event (induction failure, induction death, relapse, second malignancy, remission death) or date of last contact.

    3. Cumulative Incidence Rates of Isolated Central Nervous System (CNS) Relapse for SR and IR T-ALL Patients on the Non-bortezomib Containing Arm on This Study (no CRT) and Similar Patients on AALL0434 (Receive CRT) [3 years]

      Cumulative incidence of isolated CNS relapse adjusting for competing risks using the method of: Gray R, A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 1141:1154, 1988

    4. EFS for Very High Risk (VHR) T-ALL Patients Treated With High Risk (HR) Berlin-Frankfurt-Munster (BFM) Intensification Blocks Who Become Minimal Residual Disease (MRD) Negative and Those Who Remain MRD Positive at the End of HR Block 3 [3 years]

      EFS will be calculated as time from the end of the three high-risk blocks of therapy to first event (relapse, second malignancy, remission death) or date of last contact.

    5. EFS for Very High Risk (VHR) T-LLy Patients Treated With HR Berlin-Frankfurt-Munster (BFM) Intensification Blocks Who Have Complete or Partial Remission and Those Who do Not Respond [3 years]

      EFS for very high risk (VHR) T-LLy patients treated with HR Berlin-Frankfurt-Munster (BFM) intensification blocks who have complete or partial remission and those who do not respond

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    1 Year to 30 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • T-ALL: T-ALL patients must be enrolled on AALL08B1 or Project:EveryChild (APEC14B1, if open for the classification of ALL patients) prior to treatment and enrollment on AALL1231

    • All patients must be > 1 and < 31 years of age

    • Patients must have newly diagnosed T-lymphoblastic leukemia (T-ALL) or T-lymphoblastic lymphoma (T-LLy) stages II-IV

    • Note: 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, and are present either in peripheral blood or > 25% in the bone marrow; if surface CD3 is expressed on all leukemic cells, additional markers of immaturity, including terminal deoxynucleotidyl transferase (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

    • For T-LLy 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-LLy defined by the submitting institution will be accepted

    • All patients and/or their parents or legal guardians must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines

    Exclusion Criteria:

    • Patients must not have received any cytotoxic chemotherapy for either the current diagnosis of T-ALL, T-L-Ly or for any cancer diagnosis prior to the initiation of protocol therapy on AALL1231, with the exception of:

    • Steroid pretreatment: prednisone or methylprednisolone for =< 120 hours (5 days) in the 7 days prior to initiating induction chemotherapy or for =< 336 hours (14 days) in the 28 days prior to initiating induction chemotherapy; prior exposure to ANY steroids that occurred > 28 days before the initiation of protocol therapy does not affect eligibility; the dose of prednisone or methylprednisolone does not affect eligibility

    • Intrathecal cytarabine (the CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment) system chemotherapy must begin with 72 hours of this IT therapy; or

    • Pretreatment with hydroxyurea; or

    • 600 cGy of chest irradiation, if medically necessary

    • Pre-treatment with dexamethasone in the 28 days prior to initiation of protocol therapy is not allowed with the exception of a single dose of dexamethasone use during sedation to prevent or treat airway edema; inhalation steroids and topical steroids are not considered pretreatment

    • Pre-existing >= grade 2 sensory or motor peripheral neurotoxicity

    • Uncontrolled seizure disorder

    • Diagnosis of Down syndrome (Trisomy 21)

    • Patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential

    • Lactating females who plan to breastfeed

    • Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation

    • Patient has hypersensitivity to bortezomib, boron, or mannitol

    • Serious medical or psychiatric illness likely to interfere with participation in this clinical study

    • Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and within 30 days of any dose of bortezomib

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Children's Hospital of Alabama Birmingham Alabama United States 35233
    2 USA Health Strada Patient Care Center Mobile Alabama United States 36604
    3 Providence Alaska Medical Center Anchorage Alaska United States 99508
    4 Banner Children's at Desert Mesa Arizona United States 85202
    5 Phoenix Childrens Hospital Phoenix Arizona United States 85016
    6 Banner University Medical Center - Tucson Tucson Arizona United States 85719
    7 Arkansas Children's Hospital Little Rock Arkansas United States 72202-3591
    8 Kaiser Permanente Downey Medical Center Downey California United States 90242
    9 City of Hope Comprehensive Cancer Center Duarte California United States 91010
    10 Loma Linda University Medical Center Loma Linda California United States 92354
    11 Miller Children's and Women's Hospital Long Beach Long Beach California United States 90806
    12 Children's Hospital Los Angeles Los Angeles California United States 90027
    13 Cedars Sinai Medical Center Los Angeles California United States 90048
    14 Valley Children's Hospital Madera California United States 93636
    15 Children's Hospital and Research Center at Oakland Oakland California United States 94609-1809
    16 Kaiser Permanente-Oakland Oakland California United States 94611
    17 Children's Hospital of Orange County Orange California United States 92868
    18 Lucile Packard Children's Hospital Stanford University Palo Alto California United States 94304
    19 Sutter Medical Center Sacramento Sacramento California United States 95816
    20 University of California Davis Comprehensive Cancer Center Sacramento California United States 95817
    21 Rady Children's Hospital - San Diego San Diego California United States 92123
    22 Naval Medical Center -San Diego San Diego California United States 92134
    23 UCSF Medical Center-Mission Bay San Francisco California United States 94158
    24 Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center Torrance California United States 90502
    25 Children's Hospital Colorado Aurora Colorado United States 80045
    26 Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center Denver Colorado United States 80218
    27 Connecticut Children's Medical Center Hartford Connecticut United States 06106
    28 Yale University New Haven Connecticut United States 06520
    29 Alfred I duPont Hospital for Children Wilmington Delaware United States 19803
    30 MedStar Georgetown University Hospital Washington District of Columbia United States 20007
    31 Children's National Medical Center Washington District of Columbia United States 20010
    32 Broward Health Medical Center Fort Lauderdale Florida United States 33316
    33 Golisano Children's Hospital of Southwest Florida Fort Myers Florida United States 33908
    34 University of Florida Health Science Center - Gainesville Gainesville Florida United States 32610
    35 Memorial Regional Hospital/Joe DiMaggio Children's Hospital Hollywood Florida United States 33021
    36 Nemours Children's Clinic-Jacksonville Jacksonville Florida United States 32207
    37 University of Miami Miller School of Medicine-Sylvester Cancer Center Miami Florida United States 33136
    38 Nicklaus Children's Hospital Miami Florida United States 33155
    39 Miami Cancer Institute Miami Florida United States 33176
    40 AdventHealth Orlando Orlando Florida United States 32803
    41 Arnold Palmer Hospital for Children Orlando Florida United States 32806
    42 Nemours Children's Hospital Orlando Florida United States 32827
    43 Nemours Children's Clinic - Pensacola Pensacola Florida United States 32504
    44 Johns Hopkins All Children's Hospital Saint Petersburg Florida United States 33701
    45 Tampa General Hospital Tampa Florida United States 33606
    46 Saint Joseph's Hospital/Children's Hospital-Tampa Tampa Florida United States 33607
    47 Saint Mary's Hospital West Palm Beach Florida United States 33407
    48 Children's Healthcare of Atlanta - Egleston Atlanta Georgia United States 30322
    49 Augusta University Medical Center Augusta Georgia United States 30912
    50 Memorial Health University Medical Center Savannah Georgia United States 31404
    51 Kapiolani Medical Center for Women and Children Honolulu Hawaii United States 96826
    52 Saint Luke's Cancer Institute - Boise Boise Idaho United States 83712
    53 Lurie Children's Hospital-Chicago Chicago Illinois United States 60611
    54 University of Illinois Chicago Illinois United States 60612
    55 University of Chicago Comprehensive Cancer Center Chicago Illinois United States 60637
    56 Loyola University Medical Center Maywood Illinois United States 60153
    57 Advocate Children's Hospital-Oak Lawn Oak Lawn Illinois United States 60453
    58 Advocate Children's Hospital-Park Ridge Park Ridge Illinois United States 60068
    59 Saint Jude Midwest Affiliate Peoria Illinois United States 61637
    60 Southern Illinois University School of Medicine Springfield Illinois United States 62702
    61 Riley Hospital for Children Indianapolis Indiana United States 46202
    62 Saint Vincent Hospital and Health Care Center Indianapolis Indiana United States 46260
    63 Blank Children's Hospital Des Moines Iowa United States 50309
    64 University of Iowa/Holden Comprehensive Cancer Center Iowa City Iowa United States 52242
    65 University of Kentucky/Markey Cancer Center Lexington Kentucky United States 40536
    66 Norton Children's Hospital Louisville Kentucky United States 40202
    67 Children's Hospital New Orleans New Orleans Louisiana United States 70118
    68 Ochsner Medical Center Jefferson New Orleans Louisiana United States 70121
    69 Eastern Maine Medical Center Bangor Maine United States 04401
    70 Maine Children's Cancer Program Scarborough Maine United States 04074
    71 University of Maryland/Greenebaum Cancer Center Baltimore Maryland United States 21201
    72 Sinai Hospital of Baltimore Baltimore Maryland United States 21215
    73 Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore Maryland United States 21287
    74 Walter Reed National Military Medical Center Bethesda Maryland United States 20889-5600
    75 Tufts Children's Hospital Boston Massachusetts United States 02111
    76 Massachusetts General Hospital Cancer Center Boston Massachusetts United States 02114
    77 Baystate Medical Center Springfield Massachusetts United States 01199
    78 UMass Memorial Medical Center - University Campus Worcester Massachusetts United States 01655
    79 C S Mott Children's Hospital Ann Arbor Michigan United States 48109
    80 Wayne State University/Karmanos Cancer Institute Detroit Michigan United States 48201
    81 Ascension Saint John Hospital Detroit Michigan United States 48236
    82 Michigan State University Clinical Center East Lansing Michigan United States 48824-7016
    83 Hurley Medical Center Flint Michigan United States 48503
    84 Helen DeVos Children's Hospital at Spectrum Health Grand Rapids Michigan United States 49503
    85 Spectrum Health at Butterworth Campus Grand Rapids Michigan United States 49503
    86 Bronson Methodist Hospital Kalamazoo Michigan United States 49007
    87 West Michigan Cancer Center Kalamazoo Michigan United States 49007
    88 Beaumont Children's Hospital-Royal Oak Royal Oak Michigan United States 48073
    89 Children's Hospitals and Clinics of Minnesota - Minneapolis Minneapolis Minnesota United States 55404
    90 University of Minnesota/Masonic Cancer Center Minneapolis Minnesota United States 55455
    91 Mayo Clinic in Rochester Rochester Minnesota United States 55905
    92 University of Mississippi Medical Center Jackson Mississippi United States 39216
    93 Columbia Regional Columbia Missouri United States 65201
    94 Children's Mercy Hospitals and Clinics Kansas City Missouri United States 64108
    95 Cardinal Glennon Children's Medical Center Saint Louis Missouri United States 63104
    96 Washington University School of Medicine Saint Louis Missouri United States 63110
    97 Mercy Hospital Saint Louis Saint Louis Missouri United States 63141
    98 Children's Hospital and Medical Center of Omaha Omaha Nebraska United States 68114
    99 University of Nebraska Medical Center Omaha Nebraska United States 68198
    100 University Medical Center of Southern Nevada Las Vegas Nevada United States 89102
    101 Sunrise Hospital and Medical Center Las Vegas Nevada United States 89109
    102 Alliance for Childhood Diseases/Cure 4 the Kids Foundation Las Vegas Nevada United States 89135
    103 Summerlin Hospital Medical Center Las Vegas Nevada United States 89144
    104 Dartmouth Hitchcock Medical Center Lebanon New Hampshire United States 03756
    105 Hackensack University Medical Center Hackensack New Jersey United States 07601
    106 Morristown Medical Center Morristown New Jersey United States 07960
    107 Saint Peter's University Hospital New Brunswick New Jersey United States 08901
    108 Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital New Brunswick New Jersey United States 08903
    109 Newark Beth Israel Medical Center Newark New Jersey United States 07112
    110 Saint Joseph's Regional Medical Center Paterson New Jersey United States 07503
    111 University of New Mexico Cancer Center Albuquerque New Mexico United States 87102
    112 Albany Medical Center Albany New York United States 12208
    113 Montefiore Medical Center - Moses Campus Bronx New York United States 10467
    114 Roswell Park Cancer Institute Buffalo New York United States 14263
    115 NYU Winthrop Hospital Mineola New York United States 11501
    116 The Steven and Alexandra Cohen Children's Medical Center of New York New Hyde Park New York United States 11040
    117 Laura and Isaac Perlmutter Cancer Center at NYU Langone New York New York United States 10016
    118 Mount Sinai Hospital New York New York United States 10029
    119 NYP/Weill Cornell Medical Center New York New York United States 10065
    120 University of Rochester Rochester New York United States 14642
    121 Stony Brook University Medical Center Stony Brook New York United States 11794
    122 State University of New York Upstate Medical University Syracuse New York United States 13210
    123 New York Medical College Valhalla New York United States 10595
    124 Mission Hospital Asheville North Carolina United States 28801
    125 UNC Lineberger Comprehensive Cancer Center Chapel Hill North Carolina United States 27599
    126 Carolinas Medical Center/Levine Cancer Institute Charlotte North Carolina United States 28203
    127 Novant Health Presbyterian Medical Center Charlotte North Carolina United States 28204
    128 Duke University Medical Center Durham North Carolina United States 27710
    129 East Carolina University Greenville North Carolina United States 27834
    130 Wake Forest University Health Sciences Winston-Salem North Carolina United States 27157
    131 Sanford Broadway Medical Center Fargo North Dakota United States 58122
    132 Children's Hospital Medical Center of Akron Akron Ohio United States 44308
    133 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229
    134 Rainbow Babies and Childrens Hospital Cleveland Ohio United States 44106
    135 Cleveland Clinic Foundation Cleveland Ohio United States 44195
    136 Nationwide Children's Hospital Columbus Ohio United States 43205
    137 Dayton Children's Hospital Dayton Ohio United States 45404
    138 ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital Toledo Ohio United States 43606
    139 Mercy Children's Hospital Toledo Ohio United States 43608
    140 University of Oklahoma Health Sciences Center Oklahoma City Oklahoma United States 73104
    141 Legacy Emanuel Children's Hospital Portland Oregon United States 97227
    142 Oregon Health and Science University Portland Oregon United States 97239
    143 Lehigh Valley Hospital-Cedar Crest Allentown Pennsylvania United States 18103
    144 Lehigh Valley Hospital - Muhlenberg Bethlehem Pennsylvania United States 18017
    145 Geisinger Medical Center Danville Pennsylvania United States 17822
    146 Penn State Children's Hospital Hershey Pennsylvania United States 17033
    147 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    148 Saint Christopher's Hospital for Children Philadelphia Pennsylvania United States 19134
    149 Children's Hospital of Pittsburgh of UPMC Pittsburgh Pennsylvania United States 15224
    150 Medical University of South Carolina Charleston South Carolina United States 29425
    151 Prisma Health Richland Hospital Columbia South Carolina United States 29203
    152 BI-LO Charities Children's Cancer Center Greenville South Carolina United States 29605
    153 Sanford USD Medical Center - Sioux Falls Sioux Falls South Dakota United States 57117-5134
    154 T C Thompson Children's Hospital Chattanooga Tennessee United States 37403
    155 East Tennessee Childrens Hospital Knoxville Tennessee United States 37916
    156 The Children's Hospital at TriStar Centennial Nashville Tennessee United States 37203
    157 Vanderbilt University/Ingram Cancer Center Nashville Tennessee United States 37232
    158 Dell Children's Medical Center of Central Texas Austin Texas United States 78723
    159 Driscoll Children's Hospital Corpus Christi Texas United States 78411
    160 Medical City Dallas Hospital Dallas Texas United States 75230
    161 UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas United States 75390
    162 El Paso Children's Hospital El Paso Texas United States 79905
    163 Cook Children's Medical Center Fort Worth Texas United States 76104
    164 Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center Houston Texas United States 77030
    165 M D Anderson Cancer Center Houston Texas United States 77030
    166 Covenant Children's Hospital Lubbock Texas United States 79410
    167 UMC Cancer Center / UMC Health System Lubbock Texas United States 79415
    168 Children's Hospital of San Antonio San Antonio Texas United States 78207
    169 Methodist Children's Hospital of South Texas San Antonio Texas United States 78229
    170 University of Texas Health Science Center at San Antonio San Antonio Texas United States 78229
    171 Primary Children's Hospital Salt Lake City Utah United States 84113
    172 University of Vermont and State Agricultural College Burlington Vermont United States 05405
    173 University of Virginia Cancer Center Charlottesville Virginia United States 22908
    174 Inova Fairfax Hospital Falls Church Virginia United States 22042
    175 Children's Hospital of The King's Daughters Norfolk Virginia United States 23507
    176 Naval Medical Center - Portsmouth Portsmouth Virginia United States 23708-2197
    177 Virginia Commonwealth University/Massey Cancer Center Richmond Virginia United States 23298
    178 Carilion Children's Roanoke Virginia United States 24014
    179 Seattle Children's Hospital Seattle Washington United States 98105
    180 Providence Sacred Heart Medical Center and Children's Hospital Spokane Washington United States 99204
    181 Mary Bridge Children's Hospital and Health Center Tacoma Washington United States 98405
    182 Madigan Army Medical Center Tacoma Washington United States 98431
    183 West Virginia University Charleston Division Charleston West Virginia United States 25304
    184 West Virginia University Healthcare Morgantown West Virginia United States 26506
    185 Saint Vincent Hospital Cancer Center Green Bay Green Bay Wisconsin United States 54301
    186 University of Wisconsin Hospital and Clinics Madison Wisconsin United States 53792
    187 Marshfield Medical Center-Marshfield Marshfield Wisconsin United States 54449
    188 Children's Hospital of Wisconsin Milwaukee Wisconsin United States 53226
    189 John Hunter Children's Hospital Hunter Regional Mail Centre New South Wales Australia 2310
    190 The Children's Hospital at Westmead Westmead New South Wales Australia 2145
    191 Queensland Children's Hospital South Brisbane Queensland Australia 4101
    192 Women's and Children's Hospital-Adelaide North Adelaide South Australia Australia 5006
    193 Monash Medical Center-Clayton Campus Clayton Victoria Australia 3168
    194 Royal Children's Hospital Parkville Victoria Australia 3052
    195 Princess Margaret Hospital for Children Perth Western Australia Australia 6008
    196 Perth Children's Hospital Perth Western Australia Australia 6009
    197 Alberta Children's Hospital Calgary Alberta Canada T3B 6A8
    198 University of Alberta Hospital Edmonton Alberta Canada T6G 2B7
    199 British Columbia Children's Hospital Vancouver British Columbia Canada V6H 3V4
    200 CancerCare Manitoba Winnipeg Manitoba Canada R3E 0V9
    201 Janeway Child Health Centre Saint John's Newfoundland and Labrador Canada A1B 3V6
    202 IWK Health Centre Halifax Nova Scotia Canada B3K 6R8
    203 McMaster Children's Hospital at Hamilton Health Sciences Hamilton Ontario Canada L8N 3Z5
    204 Kingston Health Sciences Centre Kingston Ontario Canada K7L 2V7
    205 Children's Hospital London Ontario Canada N6A 5W9
    206 Children's Hospital of Eastern Ontario Ottawa Ontario Canada K1H 8L1
    207 Hospital for Sick Children Toronto Ontario Canada M5G 1X8
    208 The Montreal Children's Hospital of the MUHC Montreal Quebec Canada H3H 1P3
    209 Centre Hospitalier Universitaire Sainte-Justine Montreal Quebec Canada H3T 1C5
    210 Saskatoon Cancer Centre Saskatoon Saskatchewan Canada S7N 4H4
    211 Starship Children's Hospital Grafton Auckland New Zealand 1145
    212 Christchurch Hospital Christchurch New Zealand 8011

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: David T Teachey, Children's Oncology Group

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT02112916
    Other Study ID Numbers:
    • NCI-2014-00712
    • NCI-2014-00712
    • s14-01925
    • AALL1231
    • AALL1231
    • U10CA180886
    • U10CA098543
    First Posted:
    Apr 14, 2014
    Last Update Posted:
    Feb 23, 2022
    Last Verified:
    Jan 1, 2022
    Additional relevant MeSH terms:
    Lymphoma
    Leukemia
    Precursor Cell Lymphoblastic Leukemia-Lymphoma
    Leukemia, Lymphoid
    Lymphoma, Non-Hodgkin
    Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
    Calcium, Dietary
    Leucovorin
    Folic Acid
    Cytarabine
    Dexamethasone
    Dexamethasone acetate
    Hydrocortisone
    Hydrocortisone 17-butyrate 21-propionate
    Hydrocortisone acetate
    Hydrocortisone hemisuccinate
    Cyclophosphamide
    Ifosfamide
    Isophosphamide mustard
    Doxorubicin
    Liposomal doxorubicin
    Methotrexate
    Etoposide
    Vincristine
    Bortezomib
    Etoposide phosphate
    Daunorubicin
    Asparaginase
    Mercaptopurine
    Pegaspargase
    Podophyllotoxin
    Thioguanine
    BB 1101
    Calcium
    2-Aminopurine
    Levoleucovorin

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Arm A (Combination Chemotherapy): T-ALL Arm B (Combination Chemotherapy, Bortezomib): T-ALL Arm A (Combination Chemotherapy): T-LLy Arm B (Combination Chemotherapy, Bortezomib): T-LLy
    Arm/Group Description Patients receive combination chemotherapy without bortezomib. Patients received combination therapy with bortezomib (4 doses at 1.3mg/m2 during Induction and 4 doses at 1.3mg/m2 during Delayed Intensification) Patients receive combination chemotherapy without bortezomib. Patients received combination therapy with bortezomib (4 doses at 1.3mg/m2 during Induction and 4 doses at 1.3mg/m2 during Delayed Intensification)
    Period Title: Overall Study
    STARTED 312 315 111 109
    COMPLETED 108 123 52 62
    NOT COMPLETED 204 192 59 47

    Baseline Characteristics

    Arm/Group Title Arm A (Combination Chemotherapy): T-ALL Arm B (Combination Chemotherapy, Bortezomib): T-ALL Arm A (Combination Chemotherapy): T-LLy Arm B (Combination Chemotherapy, Bortezomib): T-LLy Total
    Arm/Group Description Patients receive combination chemotherapy without bortezomib. Patients received combination therapy with bortezomib (4 doses at 1.3mg/m2 during Induction and 4 doses at 1.3mg/m2 during Delayed Intensification) Patients receive combination chemotherapy without bortezomib. Patients received combination therapy with bortezomib (4 doses at 1.3mg/m2 during Induction and 4 doses at 1.3mg/m2 during Delayed Intensification) Total of all reporting groups
    Overall Participants 312 315 111 109 847
    Age (Count of Participants)
    <=18 years
    285
    91.3%
    296
    94%
    102
    91.9%
    97
    89%
    780
    92.1%
    Between 18 and 65 years
    27
    8.7%
    19
    6%
    9
    8.1%
    12
    11%
    67
    7.9%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    10.2
    (5.7)
    10.1
    (5.6)
    12.0
    (5.3)
    12.3
    (5.2)
    10.7
    (5.6)
    Sex: Female, Male (Count of Participants)
    Female
    64
    20.5%
    96
    30.5%
    28
    25.2%
    25
    22.9%
    213
    25.1%
    Male
    248
    79.5%
    219
    69.5%
    83
    74.8%
    84
    77.1%
    634
    74.9%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    52
    16.7%
    62
    19.7%
    17
    15.3%
    15
    13.8%
    146
    17.2%
    Not Hispanic or Latino
    236
    75.6%
    228
    72.4%
    86
    77.5%
    89
    81.7%
    639
    75.4%
    Unknown or Not Reported
    24
    7.7%
    25
    7.9%
    8
    7.2%
    5
    4.6%
    62
    7.3%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    3
    1%
    2
    0.6%
    0
    0%
    0
    0%
    5
    0.6%
    Asian
    15
    4.8%
    11
    3.5%
    5
    4.5%
    1
    0.9%
    32
    3.8%
    Native Hawaiian or Other Pacific Islander
    2
    0.6%
    1
    0.3%
    0
    0%
    0
    0%
    3
    0.4%
    Black or African American
    35
    11.2%
    37
    11.7%
    21
    18.9%
    17
    15.6%
    110
    13%
    White
    217
    69.6%
    225
    71.4%
    71
    64%
    74
    67.9%
    587
    69.3%
    More than one race
    6
    1.9%
    6
    1.9%
    1
    0.9%
    0
    0%
    13
    1.5%
    Unknown or Not Reported
    34
    10.9%
    33
    10.5%
    13
    11.7%
    17
    15.6%
    97
    11.5%
    Region of Enrollment (participants) [Number]
    United States
    294
    94.2%
    295
    93.7%
    105
    94.6%
    102
    93.6%
    796
    94%
    Canada
    12
    3.8%
    6
    1.9%
    3
    2.7%
    5
    4.6%
    26
    3.1%
    Australia
    6
    1.9%
    7
    2.2%
    3
    2.7%
    2
    1.8%
    18
    2.1%
    New Zealand
    0
    0%
    7
    2.2%
    0
    0%
    0
    0%
    7
    0.8%

    Outcome Measures

    1. Primary Outcome
    Title Event-free Survival (EFS) for Modified Augmented Berlin-Frankfurt-Munster Backbone With or Without Bortezomib in All Randomized Patients
    Description EFS is calculated as time from randomization at study entry to first event (induction failure, induction death, relapse, second malignancy, remission death) or date of last contact. Three-year EFS rates will be calculated for both groups.
    Time Frame 3 years

    Outcome Measure Data

    Analysis Population Description
    As pre-specified in the protocol, this analysis includes all eligible patients (T-ALL+T-LLy) enrolled on the study. Arms were combined for this analysis as pre-specified in the protocol.
    Arm/Group Title Arm A (Combination Chemotherapy) Arm B (Combination Chemotherapy, Bortezomib)
    Arm/Group Description Patients receive combination chemotherapy without bortezomib. Patients received combination therapy with bortezomib (4 doses at 1.3mg/m2 during Induction and 4 doses at 1.3mg/m2 during Delayed Intensification)
    Measure Participants 416 408
    Number (95% Confidence Interval) [Percentage of participants]
    81.7
    26.2%
    85.1
    27%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm A (Combination Chemotherapy), Arm B (Combination Chemotherapy, Bortezomib)
    Comments To compare the EFS of the randomized patients (T-ALL+T-LLy) on Arm A vs Arm B. Study was designed to accrue 1200 eligible, evaluable randomized patients (to provide 90.5% power to detect an improvement in 4-year EFS from 85% to 90% with an alpha of 0.05 (one-sided log-rank test) (Hazard Ratio (HR)=0.6483). Study was closed to accrual early due to results from AALL0434 for nelarabine.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.074
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.782
    Confidence Interval (2-Sided) 95%
    0.561 to 1.091
    Parameter Dispersion Type:
    Value:
    Estimation Comments Hazard ratio = hazard rate for Arm B/hazard rate for Arm A
    2. Secondary Outcome
    Title Toxicity Rates Associated With Modified Standard Therapy, Including Dexamethasone and Additional Pegaspargase
    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 4.0
    Time Frame 3 years from start of therapy by patient

    Outcome Measure Data

    Analysis Population Description
    As pre-specified in the protocol, this analysis includes all eligible patients (T-ALL+T-LLy) enrolled on the study.
    Arm/Group Title Total Patients
    Arm/Group Description All the eligible patients enrolled on the study
    Measure Participants 824
    Number (95% Confidence Interval) [Percentage of participants]
    78.0
    25%
    3. Secondary Outcome
    Title EFS for Standard (SR) and Intermediate Risk (IR) T-ALL Patients on the Non-bortezomib Containing Arm on This Study (no Cranial Radiation Therapy [CRT]) and Similar Patients on AALL0434 (Received CRT)
    Description EFS is calculated as time from randomization at study entry to first event (induction failure, induction death, relapse, second malignancy, remission death) or date of last contact.
    Time Frame 3 years

    Outcome Measure Data

    Analysis Population Description
    T-ALL patients on AALL1231 who did not receive CRT or bortezomib: IR (exclude CNS3) and SR T-ALL (exclude those who met AALL0434 [NCT00408005] Low Risk definition). T-ALL on AALL0434 [NCT00408005] (who received CRT, no nelarabine) excluding Low Risk, CNS3, M3 Day 29, and EOC MRD >0.1%
    Arm/Group Title AALL1231 T-ALL Patients AALL0434 T-ALL Patients
    Arm/Group Description T-ALL patients on AALL1231 who did not receive prophylactic cranial radiation and did not receive bortezomib: Intermediate Risk T-ALL (exclude CNS3) and SR T-ALL (exclude those who met AALL0434 Low Risk definition). T-ALL patients on AALL0434 [NCT00408005] who received prophylactic cranial radiation and did not receive nelarabine (exclude Low Risk, CNS3, M3 Day 29, and EOC MRD >0.1%);
    Measure Participants 229 634
    Number (95% Confidence Interval) [Percentage of participants]
    88.3
    28.3%
    88.8
    28.2%
    4. Secondary Outcome
    Title Cumulative Incidence Rates of Isolated Central Nervous System (CNS) Relapse for SR and IR T-ALL Patients on the Non-bortezomib Containing Arm on This Study (no CRT) and Similar Patients on AALL0434 (Receive CRT)
    Description Cumulative incidence of isolated CNS relapse adjusting for competing risks using the method of: Gray R, A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 1141:1154, 1988
    Time Frame 3 years

    Outcome Measure Data

    Analysis Population Description
    T-ALL patients on AALL1231 who did not receive CRT or bortezomib: IR (exclude CNS3) and SR T-ALL (exclude those who met AALL0434 [NCT00408005] Low Risk definition). T-ALL on AALL0434 [NCT00408005](who received CRT, no nelarabine) excluding Low Risk, CNS3, M3 Day 29, and EOC MRD >0.1%
    Arm/Group Title AALL1231 T-ALL Patients AALL0434 T-ALL Patients
    Arm/Group Description T-ALL patients on AALL1231 who did not receive prophylactic cranial radiation and did not receive bortezomib: Intermediate Risk T-ALL (exclude CNS3) and SR T-ALL (exclude those who met AALL0434 Low Risk definition). T-ALL patients on AALL0434 [NCT00408005] who received prophylactic cranial radiation and did not receive nelarabine (exclude Low Risk, CNS3, M3 Day 29, and EOC MRD >0.1%);
    Measure Participants 229 634
    Isolated CNS Relapse
    3.6
    1.2%
    2.2
    0.7%
    Isolated Bone Marrow Relapse
    1.4
    0.4%
    3.0
    1%
    Combined Bone Marrow Relapse
    1.3
    0.4%
    1.8
    0.6%
    5. Secondary Outcome
    Title EFS for Very High Risk (VHR) T-ALL Patients Treated With High Risk (HR) Berlin-Frankfurt-Munster (BFM) Intensification Blocks Who Become Minimal Residual Disease (MRD) Negative and Those Who Remain MRD Positive at the End of HR Block 3
    Description EFS will be calculated as time from the end of the three high-risk blocks of therapy to first event (relapse, second malignancy, remission death) or date of last contact.
    Time Frame 3 years

    Outcome Measure Data

    Analysis Population Description
    VHR T-ALL patients who had EOC MRD >= 0.1%, completed the three high-risk blocks of therapy, and had MRD assessment done after the three high-risk blocks. MRD was not performed in T-LLy patients at end of the VHR blocks. MRD is not used in T-LLy to measure disease response. This outcome measure was pre-specified to only be assessed in the T-ALL patients.
    Arm/Group Title VHR T-ALL MRD Undetectable VHR T-ALL MRD Detectable
    Arm/Group Description VHR T-ALL patients (with end of consolidation [EOC] MRD >= 0.1%) who become MRD negative (MRD undetectable) after the three high-risk BFM blocks of therapy VHR T-ALL patients (with end of consolidation [EOC] MRD >= 0.1%) who continue to have detectable MRD after the three high-risk BFM blocks of therapy.
    Measure Participants 8 10
    Number (95% Confidence Interval) [Percentage of participants]
    25.0
    8%
    88.9
    28.2%
    6. Secondary Outcome
    Title EFS for Very High Risk (VHR) T-LLy Patients Treated With HR Berlin-Frankfurt-Munster (BFM) Intensification Blocks Who Have Complete or Partial Remission and Those Who do Not Respond
    Description EFS for very high risk (VHR) T-LLy patients treated with HR Berlin-Frankfurt-Munster (BFM) intensification blocks who have complete or partial remission and those who do not respond
    Time Frame 3 years

    Outcome Measure Data

    Analysis Population Description
    VHR T-LL patients who completed the three high-risk blocks of therapy. The T-LLy VHR patients are included in the table, but there were not enough patients to do any formal analysis, eg there was only one patient (n=1) on the study with T-LLy who had radiographic disease assessment after the intensification blocks.
    Arm/Group Title VHR T-LLy (CR/PR) VHR T-LLy (NR)
    Arm/Group Description VHR T-LLy patients who achieved complete or partial response (CR/PR) at the end of the high-risk blocks VHR T-LLy patients who did not respond (NR) at the end of the high-risk blocks
    Measure Participants 1 0
    Number (95% Confidence Interval) [Percentage of participants]
    0
    0%

    Adverse Events

    Time Frame 3 years from start of therapy by patient
    Adverse Event Reporting Description Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.
    Arm/Group Title Arm A (Combination Chemotherapy): T-ALL Arm B (Combination Chemotherapy, Bortezomib): T-ALL Arm A (Combination Chemotherapy): T-LLy Arm B (Combination Chemotherapy, Bortezomib): T-LLy
    Arm/Group Description Patients receive combination chemotherapy without bortezomib. Patients received combination therapy with bortezomib (4 doses at 1.3mg/m2 during Induction and 4 doses at 1.3mg/m2 during Delayed Intensification) Patients receive combination chemotherapy without bortezomib. Patients received combination therapy with bortezomib (4 doses at 1.3mg/m2 during Induction and 4 doses at 1.3mg/m2 during Delayed Intensification)
    All Cause Mortality
    Arm A (Combination Chemotherapy): T-ALL Arm B (Combination Chemotherapy, Bortezomib): T-ALL Arm A (Combination Chemotherapy): T-LLy Arm B (Combination Chemotherapy, Bortezomib): T-LLy
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 38/308 (12.3%) 38/307 (12.4%) 23/108 (21.3%) 9/101 (8.9%)
    Serious Adverse Events
    Arm A (Combination Chemotherapy): T-ALL Arm B (Combination Chemotherapy, Bortezomib): T-ALL Arm A (Combination Chemotherapy): T-LLy Arm B (Combination Chemotherapy, Bortezomib): T-LLy
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 56/308 (18.2%) 153/307 (49.8%) 25/108 (23.1%) 60/101 (59.4%)
    Blood and lymphatic system disorders
    Anemia 0/308 (0%) 0 2/307 (0.7%) 2 0/108 (0%) 0 1/101 (1%) 2
    Blood and lymphatic system disorders - Other, specify 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Bone marrow hypocellular 0/308 (0%) 0 0/307 (0%) 0 1/108 (0.9%) 1 0/101 (0%) 0
    Disseminated intravascular coagulation 0/308 (0%) 0 3/307 (1%) 3 0/108 (0%) 0 1/101 (1%) 1
    Febrile neutropenia 10/308 (3.2%) 12 38/307 (12.4%) 51 2/108 (1.9%) 3 15/101 (14.9%) 20
    Hemolysis 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Cardiac disorders
    Cardiac arrest 1/308 (0.3%) 1 2/307 (0.7%) 2 3/108 (2.8%) 3 0/101 (0%) 0
    Heart failure 2/308 (0.6%) 2 0/307 (0%) 0 0/108 (0%) 0 2/101 (2%) 2
    Left ventricular systolic dysfunction 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Myocardial infarction 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Sinus bradycardia 0/308 (0%) 0 0/307 (0%) 0 1/108 (0.9%) 1 0/101 (0%) 0
    Sinus tachycardia 0/308 (0%) 0 1/307 (0.3%) 2 0/108 (0%) 0 1/101 (1%) 1
    Ventricular arrhythmia 0/308 (0%) 0 0/307 (0%) 0 1/108 (0.9%) 1 0/101 (0%) 0
    Ventricular tachycardia 0/308 (0%) 0 1/307 (0.3%) 1 1/108 (0.9%) 1 0/101 (0%) 0
    Endocrine disorders
    Endocrine disorders - Other, specify 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Eye disorders
    Eye disorders - Other, specify 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Gastrointestinal disorders
    Abdominal distension 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Abdominal pain 0/308 (0%) 0 0/307 (0%) 0 1/108 (0.9%) 1 3/101 (3%) 3
    Anal ulcer 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Ascites 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Colitis 0/308 (0%) 0 2/307 (0.7%) 2 0/108 (0%) 0 1/101 (1%) 1
    Colonic perforation 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Constipation 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 2/101 (2%) 2
    Diarrhea 0/308 (0%) 0 3/307 (1%) 3 0/108 (0%) 0 0/101 (0%) 0
    Duodenal perforation 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Duodenal ulcer 0/308 (0%) 0 0/307 (0%) 0 1/108 (0.9%) 1 0/101 (0%) 0
    Dysphagia 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 1/101 (1%) 1
    Enterocolitis 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Esophageal hemorrhage 0/308 (0%) 0 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Esophagitis 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Gastric hemorrhage 1/308 (0.3%) 1 3/307 (1%) 3 0/108 (0%) 0 1/101 (1%) 1
    Gastritis 2/308 (0.6%) 2 1/307 (0.3%) 1 1/108 (0.9%) 1 0/101 (0%) 0
    Gastrointestinal disorders - Other, specify 0/308 (0%) 0 3/307 (1%) 3 0/108 (0%) 0 0/101 (0%) 0
    Ileus 0/308 (0%) 0 3/307 (1%) 3 0/108 (0%) 0 2/101 (2%) 3
    Lower gastrointestinal hemorrhage 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 2/101 (2%) 2
    Mucositis oral 3/308 (1%) 3 10/307 (3.3%) 10 1/108 (0.9%) 1 3/101 (3%) 3
    Nausea 0/308 (0%) 0 0/307 (0%) 0 1/108 (0.9%) 1 3/101 (3%) 4
    Oral pain 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Pancreatic hemorrhage 0/308 (0%) 0 2/307 (0.7%) 2 0/108 (0%) 0 0/101 (0%) 0
    Pancreatitis 2/308 (0.6%) 2 14/307 (4.6%) 16 5/108 (4.6%) 5 7/101 (6.9%) 9
    Rectal mucositis 0/308 (0%) 0 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Rectal pain 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 2/101 (2%) 2
    Rectal ulcer 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Small intestinal mucositis 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Small intestinal obstruction 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Typhlitis 0/308 (0%) 0 6/307 (2%) 8 0/108 (0%) 0 4/101 (4%) 4
    Upper gastrointestinal hemorrhage 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Vomiting 0/308 (0%) 0 6/307 (2%) 6 1/108 (0.9%) 2 3/101 (3%) 3
    General disorders
    Death NOS 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Edema face 0/308 (0%) 0 1/307 (0.3%) 1 1/108 (0.9%) 1 0/101 (0%) 0
    Edema limbs 0/308 (0%) 0 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Fatigue 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Fever 1/308 (0.3%) 1 5/307 (1.6%) 5 0/108 (0%) 0 2/101 (2%) 3
    General disorders and administration site conditions - Other, specify 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Hypothermia 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Infusion related reaction 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 2/101 (2%) 2
    Multi-organ failure 1/308 (0.3%) 1 2/307 (0.7%) 2 0/108 (0%) 0 2/101 (2%) 2
    Non-cardiac chest pain 0/308 (0%) 0 1/307 (0.3%) 1 1/108 (0.9%) 1 1/101 (1%) 1
    Hepatobiliary disorders
    Hepatic failure 1/308 (0.3%) 1 4/307 (1.3%) 4 0/108 (0%) 0 0/101 (0%) 0
    Hepatobiliary disorders - Other, specify 3/308 (1%) 3 4/307 (1.3%) 4 0/108 (0%) 0 1/101 (1%) 1
    Portal hypertension 0/308 (0%) 0 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Immune system disorders
    Allergic reaction 1/308 (0.3%) 1 1/307 (0.3%) 1 0/108 (0%) 0 1/101 (1%) 1
    Anaphylaxis 0/308 (0%) 0 7/307 (2.3%) 7 1/108 (0.9%) 1 3/101 (3%) 3
    Autoimmune disorder 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Infections and infestations
    Anorectal infection 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Bone infection 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Bronchial infection 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Catheter related infection 0/308 (0%) 0 3/307 (1%) 3 0/108 (0%) 0 1/101 (1%) 2
    Enterocolitis infectious 1/308 (0.3%) 1 2/307 (0.7%) 2 0/108 (0%) 0 0/101 (0%) 0
    Eye infection 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Hepatic infection 1/308 (0.3%) 1 0/307 (0%) 0 1/108 (0.9%) 1 0/101 (0%) 0
    Hepatitis viral 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Infections and infestations - Other, specify 5/308 (1.6%) 5 12/307 (3.9%) 15 1/108 (0.9%) 1 8/101 (7.9%) 10
    Lung infection 4/308 (1.3%) 4 5/307 (1.6%) 6 3/108 (2.8%) 3 3/101 (3%) 3
    Meningitis 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Mucosal infection 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Papulopustular rash 0/308 (0%) 0 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Sepsis 18/308 (5.8%) 20 26/307 (8.5%) 26 7/108 (6.5%) 7 11/101 (10.9%) 12
    Sinusitis 2/308 (0.6%) 2 2/307 (0.7%) 2 0/108 (0%) 0 2/101 (2%) 3
    Skin infection 1/308 (0.3%) 1 3/307 (1%) 3 0/108 (0%) 0 1/101 (1%) 1
    Soft tissue infection 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Splenic infection 0/308 (0%) 0 0/307 (0%) 0 1/108 (0.9%) 1 0/101 (0%) 0
    Upper respiratory infection 0/308 (0%) 0 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Wound infection 0/308 (0%) 0 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Injury, poisoning and procedural complications
    Fracture 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Injury, poisoning and procedural complications - Other, specify 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 1/101 (1%) 1
    Vascular access complication 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 5/101 (5%) 5
    Wound dehiscence 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Investigations
    Activated partial thromboplastin time prolonged 1/308 (0.3%) 1 4/307 (1.3%) 4 0/108 (0%) 0 0/101 (0%) 0
    Alanine aminotransferase increased 0/308 (0%) 0 14/307 (4.6%) 18 1/108 (0.9%) 1 6/101 (5.9%) 6
    Aspartate aminotransferase increased 1/308 (0.3%) 1 6/307 (2%) 8 1/108 (0.9%) 1 2/101 (2%) 2
    Blood bilirubin increased 4/308 (1.3%) 4 15/307 (4.9%) 15 2/108 (1.9%) 2 2/101 (2%) 3
    CPK increased 0/308 (0%) 0 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Cholesterol high 0/308 (0%) 0 4/307 (1.3%) 4 0/108 (0%) 0 3/101 (3%) 3
    Creatinine increased 1/308 (0.3%) 1 4/307 (1.3%) 5 0/108 (0%) 0 0/101 (0%) 0
    Electrocardiogram QT corrected interval prolonged 1/308 (0.3%) 1 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Fibrinogen decreased 0/308 (0%) 0 6/307 (2%) 6 0/108 (0%) 0 1/101 (1%) 1
    GGT increased 1/308 (0.3%) 1 4/307 (1.3%) 4 0/108 (0%) 0 0/101 (0%) 0
    INR increased 2/308 (0.6%) 2 2/307 (0.7%) 2 0/108 (0%) 0 0/101 (0%) 0
    Investigations - Other, specify 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Lipase increased 3/308 (1%) 3 7/307 (2.3%) 8 0/108 (0%) 0 1/101 (1%) 1
    Lymphocyte count decreased 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Neutrophil count decreased 1/308 (0.3%) 2 1/307 (0.3%) 1 1/108 (0.9%) 1 0/101 (0%) 0
    Platelet count decreased 1/308 (0.3%) 1 4/307 (1.3%) 4 0/108 (0%) 0 0/101 (0%) 0
    Serum amylase increased 1/308 (0.3%) 1 5/307 (1.6%) 5 0/108 (0%) 0 0/101 (0%) 0
    Urine output decreased 0/308 (0%) 0 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Weight gain 0/308 (0%) 0 2/307 (0.7%) 2 0/108 (0%) 0 0/101 (0%) 0
    Weight loss 0/308 (0%) 0 2/307 (0.7%) 2 1/108 (0.9%) 1 4/101 (4%) 4
    White blood cell decreased 0/308 (0%) 0 2/307 (0.7%) 2 0/108 (0%) 0 0/101 (0%) 0
    Metabolism and nutrition disorders
    Acidosis 0/308 (0%) 0 3/307 (1%) 3 1/108 (0.9%) 1 1/101 (1%) 1
    Anorexia 0/308 (0%) 0 0/307 (0%) 0 1/108 (0.9%) 1 2/101 (2%) 2
    Dehydration 1/308 (0.3%) 1 9/307 (2.9%) 10 1/108 (0.9%) 4 5/101 (5%) 5
    Glucose intolerance 0/308 (0%) 0 2/307 (0.7%) 2 0/108 (0%) 0 0/101 (0%) 0
    Hypercalcemia 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 1/101 (1%) 1
    Hyperglycemia 1/308 (0.3%) 1 22/307 (7.2%) 25 2/108 (1.9%) 2 3/101 (3%) 3
    Hyperkalemia 0/308 (0%) 0 3/307 (1%) 3 0/108 (0%) 0 1/101 (1%) 1
    Hypernatremia 1/308 (0.3%) 1 1/307 (0.3%) 1 1/108 (0.9%) 1 0/101 (0%) 0
    Hypertriglyceridemia 1/308 (0.3%) 1 9/307 (2.9%) 10 1/108 (0.9%) 1 4/101 (4%) 4
    Hypoalbuminemia 0/308 (0%) 0 10/307 (3.3%) 11 1/108 (0.9%) 1 6/101 (5.9%) 6
    Hypocalcemia 1/308 (0.3%) 1 3/307 (1%) 3 0/108 (0%) 0 3/101 (3%) 3
    Hypoglycemia 2/308 (0.6%) 2 4/307 (1.3%) 4 0/108 (0%) 0 1/101 (1%) 1
    Hypokalemia 0/308 (0%) 0 4/307 (1.3%) 5 1/108 (0.9%) 1 5/101 (5%) 5
    Hyponatremia 1/308 (0.3%) 1 12/307 (3.9%) 12 1/108 (0.9%) 1 7/101 (6.9%) 7
    Hypophosphatemia 0/308 (0%) 0 2/307 (0.7%) 2 0/108 (0%) 0 2/101 (2%) 2
    Metabolism and nutrition disorders - Other, specify 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Tumor lysis syndrome 1/308 (0.3%) 1 7/307 (2.3%) 7 0/108 (0%) 0 1/101 (1%) 1
    Musculoskeletal and connective tissue disorders
    Arthritis 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Avascular necrosis 0/308 (0%) 0 0/307 (0%) 0 1/108 (0.9%) 1 0/101 (0%) 0
    Back pain 0/308 (0%) 0 2/307 (0.7%) 2 0/108 (0%) 0 2/101 (2%) 2
    Chest wall pain 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Generalized muscle weakness 1/308 (0.3%) 1 1/307 (0.3%) 1 0/108 (0%) 0 2/101 (2%) 2
    Muscle weakness lower limb 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Muscle weakness upper limb 0/308 (0%) 0 2/307 (0.7%) 2 0/108 (0%) 0 0/101 (0%) 0
    Pain in extremity 0/308 (0%) 0 5/307 (1.6%) 6 0/108 (0%) 0 0/101 (0%) 0
    Leukemia secondary to oncology chemotherapy 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Myelodysplastic syndrome 0/308 (0%) 0 1/307 (0.3%) 2 0/108 (0%) 0 0/101 (0%) 0
    Treatment related secondary malignancy 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Nervous system disorders
    Aphonia 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Depressed level of consciousness 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 1/101 (1%) 1
    Dizziness 0/308 (0%) 0 2/307 (0.7%) 2 0/108 (0%) 0 1/101 (1%) 1
    Dysarthria 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Dysphasia 1/308 (0.3%) 1 2/307 (0.7%) 2 0/108 (0%) 0 0/101 (0%) 0
    Edema cerebral 1/308 (0.3%) 1 2/307 (0.7%) 2 0/108 (0%) 0 0/101 (0%) 0
    Encephalopathy 2/308 (0.6%) 2 1/307 (0.3%) 1 0/108 (0%) 0 1/101 (1%) 1
    Facial nerve disorder 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Headache 0/308 (0%) 0 5/307 (1.6%) 5 1/108 (0.9%) 1 5/101 (5%) 5
    Intracranial hemorrhage 2/308 (0.6%) 2 2/307 (0.7%) 2 1/108 (0.9%) 1 1/101 (1%) 1
    Lethargy 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Leukoencephalopathy 0/308 (0%) 0 4/307 (1.3%) 4 0/108 (0%) 0 1/101 (1%) 1
    Movements involuntary 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Nervous system disorders - Other, specify 1/308 (0.3%) 1 1/307 (0.3%) 1 0/108 (0%) 0 1/101 (1%) 1
    Paresthesia 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Peripheral motor neuropathy 1/308 (0.3%) 1 5/307 (1.6%) 5 0/108 (0%) 0 2/101 (2%) 2
    Peripheral sensory neuropathy 0/308 (0%) 0 5/307 (1.6%) 5 0/108 (0%) 0 2/101 (2%) 2
    Reversible posterior leukoencephalopathy syndrome 0/308 (0%) 0 3/307 (1%) 3 1/108 (0.9%) 1 2/101 (2%) 2
    Seizure 1/308 (0.3%) 2 6/307 (2%) 7 0/108 (0%) 0 7/101 (6.9%) 7
    Somnolence 1/308 (0.3%) 1 1/307 (0.3%) 1 0/108 (0%) 0 1/101 (1%) 1
    Stroke 0/308 (0%) 0 3/307 (1%) 3 2/108 (1.9%) 2 1/101 (1%) 1
    Syncope 0/308 (0%) 0 4/307 (1.3%) 4 1/108 (0.9%) 1 3/101 (3%) 3
    Transient ischemic attacks 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Tremor 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Vasovagal reaction 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Pregnancy, puerperium and perinatal conditions
    Pregnancy, puerperium and perinatal conditions - Other, specify 0/308 (0%) 0 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Psychiatric disorders
    Agitation 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 1/101 (1%) 1
    Anxiety 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 1/101 (1%) 1
    Confusion 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 1/101 (1%) 1
    Delirium 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Depression 1/308 (0.3%) 1 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Psychiatric disorders - Other, specify 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Suicidal ideation 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 3/308 (1%) 3 6/307 (2%) 7 1/108 (0.9%) 1 1/101 (1%) 1
    Chronic kidney disease 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Hematuria 0/308 (0%) 0 2/307 (0.7%) 2 0/108 (0%) 0 1/101 (1%) 1
    Renal and urinary disorders - Other, specify 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Renal calculi 1/308 (0.3%) 1 3/307 (1%) 3 1/108 (0.9%) 1 0/101 (0%) 0
    Reproductive system and breast disorders
    Genital edema 0/308 (0%) 0 2/307 (0.7%) 2 0/108 (0%) 0 0/101 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Adult respiratory distress syndrome 1/308 (0.3%) 1 2/307 (0.7%) 2 0/108 (0%) 0 0/101 (0%) 0
    Atelectasis 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Bronchopulmonary hemorrhage 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Cough 0/308 (0%) 0 0/307 (0%) 0 1/108 (0.9%) 1 0/101 (0%) 0
    Dyspnea 1/308 (0.3%) 1 2/307 (0.7%) 2 1/108 (0.9%) 1 2/101 (2%) 2
    Epistaxis 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 2/101 (2%) 2
    Hypoxia 0/308 (0%) 0 10/307 (3.3%) 11 0/108 (0%) 0 3/101 (3%) 4
    Nasal congestion 0/308 (0%) 0 0/307 (0%) 0 1/108 (0.9%) 1 0/101 (0%) 0
    Pharyngeal mucositis 0/308 (0%) 0 2/307 (0.7%) 2 0/108 (0%) 0 0/101 (0%) 0
    Pleural effusion 2/308 (0.6%) 2 2/307 (0.7%) 3 0/108 (0%) 0 5/101 (5%) 5
    Pleural hemorrhage 0/308 (0%) 0 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Pleuritic pain 0/308 (0%) 0 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Pneumonitis 0/308 (0%) 0 2/307 (0.7%) 3 0/108 (0%) 0 0/101 (0%) 0
    Pneumothorax 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 1/101 (1%) 1
    Pulmonary edema 0/308 (0%) 0 4/307 (1.3%) 4 0/108 (0%) 0 0/101 (0%) 0
    Respiratory failure 4/308 (1.3%) 4 5/307 (1.6%) 5 2/108 (1.9%) 2 3/101 (3%) 3
    Pruritus 0/308 (0%) 0 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Skin and subcutaneous tissue disorders
    Skin and subcutaneous tissue disorders - Other, specify 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Skin ulceration 0/308 (0%) 0 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Urticaria 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Surgical and medical procedures
    Surgical and medical procedures - Other, specify 0/308 (0%) 0 0/307 (0%) 0 1/108 (0.9%) 1 0/101 (0%) 0
    Vascular disorders
    Capillary leak syndrome 0/308 (0%) 0 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Hematoma 1/308 (0.3%) 1 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Hypertension 1/308 (0.3%) 2 2/307 (0.7%) 2 0/108 (0%) 0 0/101 (0%) 0
    Hypotension 5/308 (1.6%) 5 10/307 (3.3%) 11 1/108 (0.9%) 1 4/101 (4%) 4
    Thromboembolic event 2/308 (0.6%) 2 17/307 (5.5%) 17 1/108 (0.9%) 1 6/101 (5.9%) 6
    Vascular disorders - Other, specify 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Other (Not Including Serious) Adverse Events
    Arm A (Combination Chemotherapy): T-ALL Arm B (Combination Chemotherapy, Bortezomib): T-ALL Arm A (Combination Chemotherapy): T-LLy Arm B (Combination Chemotherapy, Bortezomib): T-LLy
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 231/308 (75%) 217/307 (70.7%) 86/108 (79.6%) 74/101 (73.3%)
    Blood and lymphatic system disorders
    Anemia 3/308 (1%) 3 3/307 (1%) 4 1/108 (0.9%) 1 1/101 (1%) 1
    Blood and lymphatic system disorders - Other, specify 2/308 (0.6%) 2 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Bone marrow hypocellular 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Disseminated intravascular coagulation 1/308 (0.3%) 1 0/307 (0%) 0 1/108 (0.9%) 1 1/101 (1%) 1
    Febrile neutropenia 16/308 (5.2%) 20 25/307 (8.1%) 29 6/108 (5.6%) 11 7/101 (6.9%) 9
    Cardiac disorders
    Cardiac arrest 1/308 (0.3%) 1 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Left ventricular systolic dysfunction 0/308 (0%) 0 1/307 (0.3%) 1 1/108 (0.9%) 1 0/101 (0%) 0
    Pericardial effusion 2/308 (0.6%) 2 0/307 (0%) 0 1/108 (0.9%) 1 0/101 (0%) 0
    Pericardial tamponade 0/308 (0%) 0 0/307 (0%) 0 1/108 (0.9%) 1 0/101 (0%) 0
    Sinus bradycardia 0/308 (0%) 0 1/307 (0.3%) 1 1/108 (0.9%) 1 0/101 (0%) 0
    Sinus tachycardia 0/308 (0%) 0 2/307 (0.7%) 2 0/108 (0%) 0 0/101 (0%) 0
    Supraventricular tachycardia 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Ventricular arrhythmia 0/308 (0%) 0 0/307 (0%) 0 1/108 (0.9%) 1 0/101 (0%) 0
    Ventricular tachycardia 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Eye disorders
    Blurred vision 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Optic nerve disorder 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Photophobia 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Gastrointestinal disorders
    Abdominal distension 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Abdominal pain 0/308 (0%) 0 3/307 (1%) 3 0/108 (0%) 0 0/101 (0%) 0
    Anal mucositis 1/308 (0.3%) 1 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Anal pain 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Ascites 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Colitis 2/308 (0.6%) 2 0/307 (0%) 0 1/108 (0.9%) 1 1/101 (1%) 1
    Colonic perforation 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Constipation 0/308 (0%) 0 4/307 (1.3%) 4 0/108 (0%) 0 0/101 (0%) 0
    Diarrhea 1/308 (0.3%) 2 3/307 (1%) 5 0/108 (0%) 0 0/101 (0%) 0
    Dysphagia 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Enterocolitis 2/308 (0.6%) 2 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Esophagitis 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Gastric hemorrhage 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Gastrointestinal disorders - Other, specify 0/308 (0%) 0 1/307 (0.3%) 2 0/108 (0%) 0 0/101 (0%) 0
    Ileus 4/308 (1.3%) 4 5/307 (1.6%) 5 1/108 (0.9%) 1 1/101 (1%) 1
    Lower gastrointestinal hemorrhage 0/308 (0%) 0 0/307 (0%) 0 1/108 (0.9%) 1 0/101 (0%) 0
    Mucositis oral 60/308 (19.5%) 68 56/307 (18.2%) 61 23/108 (21.3%) 25 24/101 (23.8%) 32
    Nausea 0/308 (0%) 0 2/307 (0.7%) 2 0/108 (0%) 0 0/101 (0%) 0
    Pancreatitis 23/308 (7.5%) 30 29/307 (9.4%) 32 15/108 (13.9%) 20 11/101 (10.9%) 14
    Proctitis 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Rectal mucositis 0/308 (0%) 0 0/307 (0%) 0 1/108 (0.9%) 1 0/101 (0%) 0
    Rectal pain 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Retroperitoneal hemorrhage 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Small intestinal mucositis 0/308 (0%) 0 1/307 (0.3%) 1 1/108 (0.9%) 1 0/101 (0%) 0
    Small intestinal obstruction 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Typhlitis 7/308 (2.3%) 7 2/307 (0.7%) 2 0/108 (0%) 0 1/101 (1%) 1
    Vomiting 1/308 (0.3%) 1 2/307 (0.7%) 2 0/108 (0%) 0 1/101 (1%) 1
    General disorders
    Death NOS 16/308 (5.2%) 16 15/307 (4.9%) 15 10/108 (9.3%) 10 1/101 (1%) 1
    Edema face 0/308 (0%) 0 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Edema limbs 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 2/101 (2%) 2
    Facial pain 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Fever 1/308 (0.3%) 1 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Flu like symptoms 0/308 (0%) 0 0/307 (0%) 0 1/108 (0.9%) 1 0/101 (0%) 0
    General disorders and administration site conditions - Other, specify 0/308 (0%) 0 1/307 (0.3%) 1 1/108 (0.9%) 1 0/101 (0%) 0
    Hypothermia 0/308 (0%) 0 0/307 (0%) 0 1/108 (0.9%) 1 0/101 (0%) 0
    Infusion related reaction 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Multi-organ failure 2/308 (0.6%) 2 1/307 (0.3%) 1 1/108 (0.9%) 1 0/101 (0%) 0
    Pain 0/308 (0%) 0 2/307 (0.7%) 2 1/108 (0.9%) 1 0/101 (0%) 0
    Sudden death NOS 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Hepatobiliary disorders
    Cholecystitis 1/308 (0.3%) 1 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Gallbladder pain 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Hepatic failure 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Portal vein thrombosis 0/308 (0%) 0 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Immune system disorders
    Allergic reaction 19/308 (6.2%) 19 12/307 (3.9%) 12 8/108 (7.4%) 8 1/101 (1%) 1
    Anaphylaxis 7/308 (2.3%) 8 10/307 (3.3%) 11 3/108 (2.8%) 3 6/101 (5.9%) 6
    Immune system disorders - Other, specify 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Infections and infestations
    Anorectal infection 1/308 (0.3%) 1 2/307 (0.7%) 2 0/108 (0%) 0 0/101 (0%) 0
    Appendicitis 0/308 (0%) 0 3/307 (1%) 3 0/108 (0%) 0 0/101 (0%) 0
    Appendicitis perforated 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Bladder infection 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Bone infection 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Catheter related infection 3/308 (1%) 3 1/307 (0.3%) 1 1/108 (0.9%) 1 0/101 (0%) 0
    Device related infection 0/308 (0%) 0 0/307 (0%) 0 1/108 (0.9%) 1 0/101 (0%) 0
    Endocarditis infective 0/308 (0%) 0 2/307 (0.7%) 2 1/108 (0.9%) 1 0/101 (0%) 0
    Enterocolitis infectious 2/308 (0.6%) 2 1/307 (0.3%) 1 0/108 (0%) 0 3/101 (3%) 3
    Infections and infestations - Other, specify 16/308 (5.2%) 17 24/307 (7.8%) 31 5/108 (4.6%) 6 5/101 (5%) 5
    Infective myositis 0/308 (0%) 0 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Lung infection 6/308 (1.9%) 6 3/307 (1%) 3 1/108 (0.9%) 1 4/101 (4%) 4
    Meningitis 2/308 (0.6%) 2 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Mucosal infection 0/308 (0%) 0 0/307 (0%) 0 1/108 (0.9%) 1 0/101 (0%) 0
    Periorbital infection 0/308 (0%) 0 2/307 (0.7%) 2 0/108 (0%) 0 0/101 (0%) 0
    Sepsis 31/308 (10.1%) 34 20/307 (6.5%) 20 10/108 (9.3%) 12 12/101 (11.9%) 14
    Sinusitis 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Skin infection 1/308 (0.3%) 1 2/307 (0.7%) 2 0/108 (0%) 0 1/101 (1%) 1
    Small intestine infection 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Soft tissue infection 0/308 (0%) 0 2/307 (0.7%) 2 0/108 (0%) 0 0/101 (0%) 0
    Tooth infection 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Upper respiratory infection 0/308 (0%) 0 3/307 (1%) 3 0/108 (0%) 0 2/101 (2%) 2
    Urinary tract infection 0/308 (0%) 0 2/307 (0.7%) 2 0/108 (0%) 0 0/101 (0%) 0
    Wound infection 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 1/101 (1%) 1
    Injury, poisoning and procedural complications
    Vascular access complication 4/308 (1.3%) 5 1/307 (0.3%) 2 3/108 (2.8%) 3 1/101 (1%) 1
    Investigations
    Activated partial thromboplastin time prolonged 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Alanine aminotransferase increased 11/308 (3.6%) 13 15/307 (4.9%) 21 5/108 (4.6%) 6 6/101 (5.9%) 11
    Alkaline phosphatase increased 0/308 (0%) 0 2/307 (0.7%) 2 0/108 (0%) 0 0/101 (0%) 0
    Aspartate aminotransferase increased 2/308 (0.6%) 2 5/307 (1.6%) 5 2/108 (1.9%) 2 5/101 (5%) 5
    Blood antidiuretic hormone abnormal 0/308 (0%) 0 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Blood bilirubin increased 42/308 (13.6%) 57 50/307 (16.3%) 78 20/108 (18.5%) 24 12/101 (11.9%) 17
    Cholesterol high 1/308 (0.3%) 1 2/307 (0.7%) 3 1/108 (0.9%) 1 2/101 (2%) 2
    Creatinine increased 2/308 (0.6%) 2 2/307 (0.7%) 2 1/108 (0.9%) 1 0/101 (0%) 0
    Fibrinogen decreased 4/308 (1.3%) 5 3/307 (1%) 3 1/108 (0.9%) 1 1/101 (1%) 1
    GGT increased 5/308 (1.6%) 5 7/307 (2.3%) 7 0/108 (0%) 0 0/101 (0%) 0
    Investigations - Other, specify 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Lipase increased 13/308 (4.2%) 16 13/307 (4.2%) 14 5/108 (4.6%) 6 4/101 (4%) 6
    Lymphocyte count decreased 1/308 (0.3%) 1 1/307 (0.3%) 1 0/108 (0%) 0 1/101 (1%) 1
    Neutrophil count decreased 4/308 (1.3%) 6 10/307 (3.3%) 18 3/108 (2.8%) 5 2/101 (2%) 2
    Platelet count decreased 3/308 (1%) 3 6/307 (2%) 8 1/108 (0.9%) 1 1/101 (1%) 1
    Serum amylase increased 1/308 (0.3%) 1 1/307 (0.3%) 1 1/108 (0.9%) 2 1/101 (1%) 1
    Urine output decreased 0/308 (0%) 0 2/307 (0.7%) 2 0/108 (0%) 0 0/101 (0%) 0
    Weight gain 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Weight loss 1/308 (0.3%) 1 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    White blood cell decreased 2/308 (0.6%) 2 2/307 (0.7%) 3 0/108 (0%) 0 0/101 (0%) 0
    Metabolism and nutrition disorders
    Acidosis 2/308 (0.6%) 2 0/307 (0%) 0 2/108 (1.9%) 2 0/101 (0%) 0
    Anorexia 4/308 (1.3%) 4 3/307 (1%) 3 2/108 (1.9%) 2 0/101 (0%) 0
    Dehydration 1/308 (0.3%) 1 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Hypercalcemia 1/308 (0.3%) 1 3/307 (1%) 3 0/108 (0%) 0 0/101 (0%) 0
    Hyperglycemia 19/308 (6.2%) 22 18/307 (5.9%) 21 2/108 (1.9%) 2 1/101 (1%) 1
    Hyperkalemia 6/308 (1.9%) 6 6/307 (2%) 6 2/108 (1.9%) 2 0/101 (0%) 0
    Hypernatremia 2/308 (0.6%) 2 1/307 (0.3%) 1 1/108 (0.9%) 1 2/101 (2%) 2
    Hypertriglyceridemia 10/308 (3.2%) 15 13/307 (4.2%) 16 6/108 (5.6%) 7 7/101 (6.9%) 10
    Hyperuricemia 3/308 (1%) 3 1/307 (0.3%) 1 1/108 (0.9%) 1 0/101 (0%) 0
    Hypoalbuminemia 2/308 (0.6%) 3 2/307 (0.7%) 2 1/108 (0.9%) 1 0/101 (0%) 0
    Hypocalcemia 11/308 (3.6%) 11 8/307 (2.6%) 8 4/108 (3.7%) 4 1/101 (1%) 1
    Hypoglycemia 4/308 (1.3%) 4 3/307 (1%) 3 0/108 (0%) 0 1/101 (1%) 1
    Hypokalemia 22/308 (7.1%) 25 21/307 (6.8%) 24 7/108 (6.5%) 9 6/101 (5.9%) 6
    Hyponatremia 50/308 (16.2%) 58 55/307 (17.9%) 59 21/108 (19.4%) 24 16/101 (15.8%) 17
    Hypophosphatemia 33/308 (10.7%) 39 26/307 (8.5%) 30 10/108 (9.3%) 13 12/101 (11.9%) 12
    Metabolism and nutrition disorders - Other, specify 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Obesity 0/308 (0%) 0 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Tumor lysis syndrome 7/308 (2.3%) 7 4/307 (1.3%) 4 0/108 (0%) 0 0/101 (0%) 0
    Musculoskeletal and connective tissue disorders
    Avascular necrosis 30/308 (9.7%) 47 25/307 (8.1%) 34 13/108 (12%) 17 12/101 (11.9%) 14
    Back pain 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Muscle weakness lower limb 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Musculoskeletal and connective tissue disorder - Other, specify 2/308 (0.6%) 2 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Pain in extremity 0/308 (0%) 0 2/307 (0.7%) 2 0/108 (0%) 0 1/101 (1%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify 3/308 (1%) 4 2/307 (0.7%) 2 6/108 (5.6%) 7 3/101 (3%) 3
    Nervous system disorders
    Cerebrospinal fluid leakage 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Dysarthria 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Encephalopathy 8/308 (2.6%) 8 2/307 (0.7%) 2 1/108 (0.9%) 1 5/101 (5%) 5
    Headache 0/308 (0%) 0 2/307 (0.7%) 2 0/108 (0%) 0 0/101 (0%) 0
    Intracranial hemorrhage 2/308 (0.6%) 2 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Leukoencephalopathy 2/308 (0.6%) 2 1/307 (0.3%) 1 3/108 (2.8%) 3 1/101 (1%) 1
    Nervous system disorders - Other, specify 1/308 (0.3%) 1 3/307 (1%) 3 0/108 (0%) 0 0/101 (0%) 0
    Paresthesia 0/308 (0%) 0 2/307 (0.7%) 2 0/108 (0%) 0 0/101 (0%) 0
    Peripheral motor neuropathy 27/308 (8.8%) 30 26/307 (8.5%) 34 13/108 (12%) 16 2/101 (2%) 2
    Peripheral sensory neuropathy 20/308 (6.5%) 32 27/307 (8.8%) 36 8/108 (7.4%) 10 7/101 (6.9%) 8
    Presyncope 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Reversible posterior leukoencephalopathy syndrome 4/308 (1.3%) 4 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Seizure 17/308 (5.5%) 19 10/307 (3.3%) 10 4/108 (3.7%) 8 6/101 (5.9%) 6
    Stroke 0/308 (0%) 0 1/307 (0.3%) 1 1/108 (0.9%) 1 0/101 (0%) 0
    Transient ischemic attacks 0/308 (0%) 0 1/307 (0.3%) 1 1/108 (0.9%) 1 0/101 (0%) 0
    Tremor 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Psychiatric disorders
    Agitation 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Delirium 0/308 (0%) 0 1/307 (0.3%) 1 1/108 (0.9%) 1 0/101 (0%) 0
    Depression 1/308 (0.3%) 1 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Psychosis 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Suicidal ideation 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Suicide attempt 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 4/308 (1.3%) 4 4/307 (1.3%) 4 4/108 (3.7%) 4 0/101 (0%) 0
    Hematuria 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Renal calculi 2/308 (0.6%) 2 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Atelectasis 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Bronchopulmonary hemorrhage 0/308 (0%) 0 0/307 (0%) 0 1/108 (0.9%) 1 0/101 (0%) 0
    Dyspnea 0/308 (0%) 0 2/307 (0.7%) 2 0/108 (0%) 0 0/101 (0%) 0
    Hypoxia 2/308 (0.6%) 2 1/307 (0.3%) 1 2/108 (1.9%) 2 0/101 (0%) 0
    Laryngeal mucositis 1/308 (0.3%) 3 0/307 (0%) 0 0/108 (0%) 0 1/101 (1%) 1
    Laryngospasm 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Pleural effusion 3/308 (1%) 3 1/307 (0.3%) 1 1/108 (0.9%) 1 0/101 (0%) 0
    Pleuritic pain 0/308 (0%) 0 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Pneumonitis 2/308 (0.6%) 2 0/307 (0%) 0 1/108 (0.9%) 1 0/101 (0%) 0
    Pneumothorax 0/308 (0%) 0 0/307 (0%) 0 1/108 (0.9%) 1 0/101 (0%) 0
    Pulmonary edema 1/308 (0.3%) 1 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Respiratory failure 4/308 (1.3%) 4 1/307 (0.3%) 1 4/108 (3.7%) 4 2/101 (2%) 2
    Skin and subcutaneous tissue disorders
    Rash maculo-papular 1/308 (0.3%) 1 1/307 (0.3%) 1 0/108 (0%) 0 0/101 (0%) 0
    Vascular disorders
    Hypertension 1/308 (0.3%) 1 3/307 (1%) 3 0/108 (0%) 0 1/101 (1%) 1
    Hypotension 8/308 (2.6%) 8 6/307 (2%) 6 3/108 (2.8%) 3 3/101 (3%) 3
    Superficial thrombophlebitis 1/308 (0.3%) 1 0/307 (0%) 0 0/108 (0%) 0 0/101 (0%) 0
    Thromboembolic event 13/308 (4.2%) 14 7/307 (2.3%) 7 11/108 (10.2%) 13 1/101 (1%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Results Reporting Coordinator
    Organization Children's Oncology Group
    Phone 16264470064
    Email resultsreportingcoordinator@childrensoncologygroup.org
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT02112916
    Other Study ID Numbers:
    • NCI-2014-00712
    • NCI-2014-00712
    • s14-01925
    • AALL1231
    • AALL1231
    • U10CA180886
    • U10CA098543
    First Posted:
    Apr 14, 2014
    Last Update Posted:
    Feb 23, 2022
    Last Verified:
    Jan 1, 2022