Calaspargase Pegol or Pegaspargase and Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia

Sponsor
Children's Oncology Group (Other)
Overall Status
Completed
CT.gov ID
NCT00671034
Collaborator
National Cancer Institute (NCI) (NIH)
166
27
2
152.3
6.1
0

Study Details

Study Description

Brief Summary

This randomized clinical trial is studying giving calaspargase pegol together with combination chemotherapy to see how well it works compared with giving pegaspargase together with combination chemotherapy in treating younger patients with newly diagnosed high-risk acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

PRIMARY OBJECTIVES:
  1. To determine the pharmacokinetic comparability of EZN-2285 (calaspargase pegol) compared to Oncaspar (pegaspargase) given intravenously during induction and consolidation in patients with high-risk ALL receiving augmented Berlin-Frankfurt-Munster (BFM) therapy.
SECONDARY OBJECTIVES:
  1. To describe the pharmacodynamics (PD) of EZN-2285 compared to Oncaspar given intravenously during induction and consolidation in patients with high-risk ALL receiving augmented BFM therapy.

  2. To determine end of induction therapy day 29 minimal residual disease (MRD) for patients randomized to the EZN-2285 containing regimen compared to the Oncaspar® containing regimen.

  3. To determine the complete remission (CR) rates for patients receiving EZN-2285 by day 29 of induction compared to Oncaspar.

  4. To assess event-free survival (EFS) associated with the administration of EZN-2285 given during augmented post Induction intensification therapy to patients with high-risk ALL compared to Oncaspar.

  5. To determine the proportion of patients with an asparaginase level of at least 0.1 IU/mL and the proportion with at least 0.4 IU/mL on days 4, 15, 22 and 29 of induction compared to Oncaspar.

  6. To determine the plasma and cerebrospinal fluid (CSF) concentrations of asparagine after administration of EZN-2285 compared to Oncaspar.

  7. To assess the immunogenicity of EZN-2285 including the detection of binding and neutralizing antibodies compared to Oncaspar.

  8. To assess the tolerability and toxicities associated with the administration of EZN-2285 given during augmented post induction intensification therapy to patients with high risk ALL compared to Oncaspar.

  9. To explore the relationship between the terminal pharmacokinetics (PK) of EZN-2285 and the presence of antibodies.

OUTLINE: This is a multicenter study. Patients are stratified according to response to induction therapy (slow early responders [SER] vs rapid early responders [RER]. Patients are randomized to 1 of 2 treatment arms in 2:1 ratio (arm I: arm II) (patients randomized to arm I receive study drug calaspargase pegol*; patients randomized to arm II receive study drug pegaspargase).

INDUCTION THERAPY** (ALL PATIENTS): Patients receive cytarabine intrathecally (IT) on day 1; vincristine intravenously (IV) and daunorubicin hydrochloride IV over 15 minutes on days 1, 8, 15, and 22; prednisone orally or IV twice daily (BID) on days 1-28; study drug IV over 1 hour on day 4; and methotrexate IT on days 8, 15*, 22*, and 29. Patients are assessed for response on day 8 and/or day 15 and day 29. Patients who achieve M1 marrow on day 8 or 15 and negative MRD (i.e., < 0.1%) on day 29 are considered RER. Patients who achieve M2 or M3 marrow on day 15 OR MRD >= 0.1% but < 1% on day 29 are considered SER. Patients with M3 bone marrow are removed from the study. RER and SER proceed to consolidation therapy. Patients with M2 marrow or M1 marrow with >= 1% MRD receive extended induction therapy. Patients also receive dexamethasone PO or IV BID on days 1-14 (patients < 10 years) or prednisone BID on days 1-28 (patients >= 10 years)

NOTE: *For patients with CNS3 disease only.

EXTENDED INDUCTION THERAPY**: Patients receive vincristine IV on days 1 and 8; prednisone orally (PO) or IV BID on days 1-14; daunorubicin hydrochloride IV over 15 minutes on day 1; and study drug IV over 1 hour on day 4. Patients are assessed for response on day 43. Patients who achieve M1 and MRD < 1% are treated as SER (proceed to consolidation therapy). All other patients are removed from study.

CONSOLIDATION THERAPY** (ALL PATIENTS): Beginning on day 36 (after completion of induction therapy) or after completion of extended induction therapy, patients (RER and SER) receive cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine IV or SC on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO on days 1-14 and 29-42; vincristine IV on days 15, 22, 43, and 50; study drug IV over 1 hour on days 15 and 43; and methotrexate IT on days 1, 8, 15*, and 22*. Patients then proceed to interim maintenance I therapy.

NOTE: *Omit doses for patients with CNS3 disease.

INTERIM MAINTENANCE I** (ALL PATIENTS): Patients receive vincristine IV and methotrexate** IV on days 1, 11, 21, 31, and 41; study drug IV over 1 hour on days 2 and 22; and methotrexate IT on days 1 and 31. Patients then proceed to delayed intensification I therapy.

DELAYED INTENSIFICATION I** (ALL PATIENTS): Patients receive vincristine IV on days 1, 8, 15, 43, and 50; dexamethasone PO or IV BID on days 1-21 for patients age 1-9, or on days 1-7 and 15-21 for patients age >= 10; doxorubicin hydrochloride IV over 15 minutes on days 1, 8, and 15; study drug IV over 1 hour on days 4 and 43; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV or subcutaneously (SC) on days 29-32 and 36-39; thioguanine PO on days 29-42; and methotrexate IT on days 1, 29, and 36. Patients treated as RER proceed to maintenance therapy. Patients treated as SER (i.e., patients with CNS3 disease at diagnosis, or pre-treated with steroids, or who are RERs with mixed lineage leukemia [MLL] gene rearrangements) proceed to interim maintenance II followed by delayed intensification II.

INTERIM MAINTENANCE II** (SER ONLY): Patients receive vincristine IV, methotrexate IV, study drug IV, and methotrexate IT as in interim maintenance I.

DELAYED INTENSIFICATION II** (SER ONLY): Beginning on day 29, patients (except patients with CNS3 disease) receive 8 daily fractions of cranial radiotherapy. All patients then receive vincristine IV, dexamethasone PO or IV, doxorubicin hydrochloride IV, study drug IV, cyclophosphamide IV, cytarabine IV or SC, thioguanine PO, and methotrexate IT as in delayed intensification I. Patients who were initially diagnosed with CNS3 disease receive cranial radiotherapy on days 1-5 and 8-12. Patients then proceed to maintenance therapy.

MAINTENANCE THERAPY** (ALL PATIENTS): Patients receive vincristine IV on days 1, 29, and 57; oral dexamethasone on days 1-5, 29-33, and 57-61; mercaptopurine PO on days 1-84; methotrexate IT on day 29; and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 12 weeks for up to 2 years (for female patients) or up to 3 years (for male patients) from the start of interim maintenance I.

NOTE: ** As per amendment #4, most patients receive high-dose methotrexate instead of Capizzi methotrexate at most stages of therapy. CNS3 patients and SER patients who have received cranial irradiation receive planned therapy with no modifications.

NOTE: As per amendment #4, the maximum number of intrathecal treatments is limited by RER/SER/CNS3 status and gender.

Blood and cerebrospinal fluid samples are collected periodically for correlative studies, including immunogenicity, pharmacokinetic, and pharmacodynamic studies.

After completion of study therapy, patients are followed every 2 months for 2 years, every 3 months for 1 year, and then every 6-12 months for 2 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
166 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Pilot Study of Intravenous EZN-2285 (SC-PEG E. Coli L-asparaginase) or Intravenous Oncaspar® in the Treatment of Patients With High-Risk Acute Lymphoblastic Leukemia (ALL)
Actual Study Start Date :
Jul 21, 2008
Actual Primary Completion Date :
Feb 1, 2011
Actual Study Completion Date :
Mar 31, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm I (combination chemotherapy)

Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 4 years.

Drug: Calaspargase Pegol-mknl
Given IV
Other Names:
  • Asparaginase (Escherichia coli Isoenzyme II), Conjugate with alpha-(((2,5-Dioxo-1-pyrrolidinyl)oxy)carbonyl)-omega-methoxypoly(oxy-1,2-ethanediyl)
  • Asparlas
  • Calaspargase Pegol
  • EZN-2285
  • SC-PEG E. Coli L-Asparaginase
  • Succinimidyl Carbonate Monomethoxypolyethylene Glycol E. coli L-Asparaginase
  • 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 IV, IT, PO, 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 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 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
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Drug: Mercaptopurine
    Given 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 IV, IT, 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
  • Other: Pharmacological Study
    Correlative studies

    Drug: Prednisone
    Given IV or PO
    Other Names:
  • .delta.1-Cortisone
  • 1, 2-Dehydrocortisone
  • Adasone
  • Cortancyl
  • Dacortin
  • DeCortin
  • Decortisyl
  • Decorton
  • Delta 1-Cortisone
  • Delta-Dome
  • Deltacortene
  • Deltacortisone
  • Deltadehydrocortisone
  • Deltasone
  • Deltison
  • Deltra
  • Econosone
  • Lisacort
  • Meprosona-F
  • Metacortandracin
  • Meticorten
  • Ofisolona
  • Orasone
  • Panafcort
  • Panasol-S
  • Paracort
  • Perrigo Prednisone
  • PRED
  • Predicor
  • Predicorten
  • Prednicen-M
  • Prednicort
  • Prednidib
  • Prednilonga
  • Predniment
  • Prednisone Intensol
  • Prednisonum
  • Prednitone
  • Promifen
  • Rayos
  • Servisone
  • SK-Prednisone
  • Radiation: Radiation Therapy
    Some patients undergo RT
    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 Sulfate
    Given IV
    Other Names:
  • Kyocristine
  • Leurocristine Sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate
  • Active Comparator: Arm II (combination chemotherapy)

    Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 4 years.

    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 IV, IT, PO, 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 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 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
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Drug: Mercaptopurine
    Given 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 IV, IT, 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
  • Other: Pharmacological Study
    Correlative studies

    Drug: Prednisone
    Given IV or PO
    Other Names:
  • .delta.1-Cortisone
  • 1, 2-Dehydrocortisone
  • Adasone
  • Cortancyl
  • Dacortin
  • DeCortin
  • Decortisyl
  • Decorton
  • Delta 1-Cortisone
  • Delta-Dome
  • Deltacortene
  • Deltacortisone
  • Deltadehydrocortisone
  • Deltasone
  • Deltison
  • Deltra
  • Econosone
  • Lisacort
  • Meprosona-F
  • Metacortandracin
  • Meticorten
  • Ofisolona
  • Orasone
  • Panafcort
  • Panasol-S
  • Paracort
  • Perrigo Prednisone
  • PRED
  • Predicor
  • Predicorten
  • Prednicen-M
  • Prednicort
  • Prednidib
  • Prednilonga
  • Predniment
  • Prednisone Intensol
  • Prednisonum
  • Prednitone
  • Promifen
  • Rayos
  • Servisone
  • SK-Prednisone
  • Radiation: Radiation Therapy
    Some patients undergo RT
    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 Sulfate
    Given IV
    Other Names:
  • Kyocristine
  • Leurocristine Sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate
  • Outcome Measures

    Primary Outcome Measures

    1. Pharmacokinetics (PK) (Half-life of SC-PEG E. Coli L-asparaginase (EZN-2285) Compared to Pegaspargase During Induction and Consolidation Therapy) [Post Day 29 of Induction and Post Day 22 of Consolidation]

      Mean half-life of plasma asparaginase during consolidation and Induction; half-life is defined as the time taken for drug concentration to decrease by half.

    Secondary Outcome Measures

    1. Pharmacodynamics (PD) [Day 29 of consolidation and induction]

      Plasma Asparaginase Concentration During consolidation and induction.

    2. Percentage of Participants With Minimal Residual Disease (MRD)<0.01% at the End of Induction [End of induction (Day 29)]

      Percentage of participants with Negative MRD (MRD<0.01%).

    3. Percentage of Participants With Complete Remission at the End of Induction [End of induction (Day 29)]

      Complete Remission (CR) rate; where CR is defined as M1 marrow (< 5% lymphoblasts in the bone marrow)

    4. Percentage of Participants With Event-free Survival (EFS) [5 Years]

      Percentage of participants who were event free. Event Free Probability defined as time from randomization at study entry to first event (induction failure, induction death, relapse, second malignant neoplasm, remission death) or date of last contact for subjects who are event-free.

    5. Asparaginase Level [Days 4, 15, 22 and 29 of Induction]

      The proportion of patients with an asparaginase level of at least 0.1 IU/mL and the proportion with at least 0.4 IU/mL on Days 4, 15, 22 and 29 of Induction compared to Oncaspar

    6. Plasma and CSF Concentrations of Asparagine in ug/ml [25 Days Post-dose (Day 29)]

      The plasma and CSF concentrations of asparagine in ug/ml after administration of EZN-2285 compared to Oncaspar.

    7. Immunogenicity [25 Days Post-dose (Day 29)]

      Number of Patients with Positive Immunogenicity tests

    8. Toxicities During Post Induction Intensification Therapy (All Grades) [Up to 5 years]

      The calculation of AE incidence will be based on the number of patients per AE category. For each patient who has multiple AEs classified to the same category, that patient will be tabulated under the worst toxicity grade for that AE category. The incidence of AEs will be tabulated by treatment arm and by organ class. Special attention will be paid to hypersensitivity, pancreatitis, coagulopathy, infection, neurologic dysfunction and thromboembolic events.

    9. Relationship Between PK and Presence of Antibodies [Day 29 of consolidation]

      Patients with presence of Antibodies.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    2 Years to 30 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients must be eligible for and enrolled on AALL08B1 or the successor classification study

    • Patients must have newly diagnosed high-risk B lymphoblastic leukemia (World Health Organization [WHO] 2008 classification) (also termed B-precursor acute lymphoblastic leukemia)

    • White blood cell (WBC) >= 50,000/μL for patients age 1-9 OR any WBC count for patients age 10-30 or for patients treated with prior steroids

    • Patients shall have had no prior cytotoxic chemotherapy with the exception of steroids and intrathecal cytarabine; intrathecal chemotherapy with cytarabine is allowed prior to registration for patient convenience; this is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture; (Note: the CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment) systemic chemotherapy must begin within 72 hours of this intrathecal therapy

    • Patients receiving prior steroid therapy are eligible for this study; the dose and duration of previous steroid therapy should be carefully documented

    • Pregnancy tests with a negative result must be obtained in all post-menarchal females

    • Lactating females must agree that they will not breastfeed a child while on this study

    Exclusion Criteria:
    • Patients with Down syndrome are excluded from this study

    • Patients with testicular leukemia at diagnosis are excluded from this study

    • Pregnant female patients are excluded from this study

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Cancer Center Birmingham Alabama United States 35233
    2 Children's Hospital of Orange County Orange California United States 92868
    3 Lucile Packard Children's Hospital Stanford University Palo Alto California United States 94304
    4 Children's Hospital Colorado Aurora Colorado United States 80045
    5 University of Connecticut Farmington Connecticut United States 06030
    6 Connecticut Children's Medical Center Hartford Connecticut United States 06106
    7 Children's National Medical Center Washington District of Columbia United States 20010
    8 Lurie Children's Hospital-Chicago Chicago Illinois United States 60611
    9 Indiana University/Melvin and Bren Simon Cancer Center Indianapolis Indiana United States 46202
    10 Riley Hospital for Children Indianapolis Indiana United States 46202
    11 Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore Maryland United States 21287
    12 Wayne State University/Karmanos Cancer Institute Detroit Michigan United States 48201
    13 Children's Hospitals and Clinics of Minnesota - Minneapolis Minneapolis Minnesota United States 55404
    14 University of Minnesota/Masonic Cancer Center Minneapolis Minnesota United States 55455
    15 Washington University School of Medicine Saint Louis Missouri United States 63110
    16 Hackensack University Medical Center Hackensack New Jersey United States 07601
    17 University of New Mexico Cancer Center Albuquerque New Mexico United States 87102
    18 Laura and Isaac Perlmutter Cancer Center at NYU Langone New York New York United States 10016
    19 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229
    20 University of Oklahoma Health Sciences Center Oklahoma City Oklahoma United States 73104
    21 Oregon Health and Science University Portland Oregon United States 97239
    22 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    23 Children's Hospital of Pittsburgh of UPMC Pittsburgh Pennsylvania United States 15224
    24 Vanderbilt University/Ingram Cancer Center Nashville Tennessee United States 37232
    25 UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas United States 75390
    26 Primary Children's Hospital Salt Lake City Utah United States 84113
    27 Seattle Children's Hospital Seattle Washington United States 98105

    Sponsors and Collaborators

    • Children's Oncology Group
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Anne L Angiolillo, Children's Oncology Group

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Children's Oncology Group
    ClinicalTrials.gov Identifier:
    NCT00671034
    Other Study ID Numbers:
    • AALL07P4
    • NCI-2009-00317
    • CDR0000594340
    • 08-606
    • COG-AALL07P4
    • AALL07P4
    • AALL07P4
    • U10CA098543
    First Posted:
    May 2, 2008
    Last Update Posted:
    Apr 27, 2021
    Last Verified:
    Apr 1, 2021

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Arm I (Calaspargase Pegol 2100) Arm II (Calaspargase Pegol 2500) Arm III (Pegaspargase 2500)
    Arm/Group Description Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 3 1/2 years. Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 3 1/2 years. Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 3 1/2 years.
    Period Title: Overall Study
    STARTED 69 42 55
    COMPLETED 30 22 31
    NOT COMPLETED 39 20 24

    Baseline Characteristics

    Arm/Group Title Arm I (Calaspargase Pegol 2100) Arm II (Calaspargase Pegol 2500) Arm III (Pegaspargase 2500) Total
    Arm/Group Description calaspargase pegol 2100 calaspargase pegol 2500 pegaspargase 2500 Total of all reporting groups
    Overall Participants 69 42 55 166
    Age (Count of Participants)
    <=18 years
    62
    89.9%
    40
    95.2%
    51
    92.7%
    153
    92.2%
    Between 18 and 65 years
    7
    10.1%
    2
    4.8%
    4
    7.3%
    13
    7.8%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    11.9
    (5.58)
    9.9
    (6.09)
    10.79
    (5.54)
    11.3
    (5.72)
    Sex: Female, Male (Count of Participants)
    Female
    31
    44.9%
    28
    66.7%
    23
    41.8%
    82
    49.4%
    Male
    38
    55.1%
    14
    33.3%
    32
    58.2%
    84
    50.6%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    14
    20.3%
    12
    28.6%
    18
    32.7%
    44
    26.5%
    Not Hispanic or Latino
    53
    76.8%
    28
    66.7%
    35
    63.6%
    116
    69.9%
    Unknown or Not Reported
    2
    2.9%
    2
    4.8%
    2
    3.6%
    6
    3.6%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    4
    5.8%
    1
    2.4%
    1
    1.8%
    6
    3.6%
    Native Hawaiian or Other Pacific Islander
    1
    1.4%
    1
    2.4%
    0
    0%
    2
    1.2%
    Black or African American
    4
    5.8%
    1
    2.4%
    6
    10.9%
    11
    6.6%
    White
    56
    81.2%
    35
    83.3%
    43
    78.2%
    134
    80.7%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    4
    5.8%
    4
    9.5%
    5
    9.1%
    13
    7.8%

    Outcome Measures

    1. Primary Outcome
    Title Pharmacokinetics (PK) (Half-life of SC-PEG E. Coli L-asparaginase (EZN-2285) Compared to Pegaspargase During Induction and Consolidation Therapy)
    Description Mean half-life of plasma asparaginase during consolidation and Induction; half-life is defined as the time taken for drug concentration to decrease by half.
    Time Frame Post Day 29 of Induction and Post Day 22 of Consolidation

    Outcome Measure Data

    Analysis Population Description
    Analysis restricted to patients who had PK data collected
    Arm/Group Title Arm I (Calaspargase Pegol 2100) Arm II ( Calaspargase Pegol 2500) Arm III (Pegaspargase 2500)
    Arm/Group Description Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 3 1/2 years. Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 3 1/2 years. Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 3 1/2 years.
    Measure Participants 69 42 54
    Asparaginase half-life during Consolidation
    415.8
    (148.51)
    355.9
    (133.0)
    117.2
    (49.36)
    Asparaginase half-life during Induction
    305.1
    (98.33)
    321.5
    (118.22)
    126.9
    (50.51)
    2. Secondary Outcome
    Title Pharmacodynamics (PD)
    Description Plasma Asparaginase Concentration During consolidation and induction.
    Time Frame Day 29 of consolidation and induction

    Outcome Measure Data

    Analysis Population Description
    Patients who had data collected
    Arm/Group Title Arm I (Calaspargase Pegol 2100) Arm II (Calaspargase Pegol 2500) Arm III (Pegaspargase 2500)
    Arm/Group Description Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 3 1/2 years. Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 3 1/2 years. Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 3 1/2 years.
    Measure Participants 69 42 54
    Plasma Asparaginase Concentration- Consolidation
    575.9
    (233.91)
    617.2
    (321.41)
    562.1
    (296.82)
    Plasma Asparaginase Concentration- Induction
    271.6
    (118.17)
    339.6
    (126.83)
    72.8
    (47.94)
    3. Secondary Outcome
    Title Percentage of Participants With Minimal Residual Disease (MRD)<0.01% at the End of Induction
    Description Percentage of participants with Negative MRD (MRD<0.01%).
    Time Frame End of induction (Day 29)

    Outcome Measure Data

    Analysis Population Description
    Patients who had data collected.
    Arm/Group Title Arm I (Calaspargase Pegol 2100) Arm II (Calaspargase Pegol 2500) Arm III (Pegaspargase 2500)
    Arm/Group Description Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 3 1/2 years. Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 3 1/2 years. Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 3 1/2 years.
    Measure Participants 62 40 47
    Number (95% Confidence Interval) [Percentage of participants]
    65.2
    94.5%
    81
    192.9%
    72.5
    131.8%
    4. Secondary Outcome
    Title Percentage of Participants With Complete Remission at the End of Induction
    Description Complete Remission (CR) rate; where CR is defined as M1 marrow (< 5% lymphoblasts in the bone marrow)
    Time Frame End of induction (Day 29)

    Outcome Measure Data

    Analysis Population Description
    Patients who had data collected
    Arm/Group Title Arm I (Calaspargase Pegol 2100) Arm II (Calaspargase Pegol 2500) Arm III (Pegaspargase 2500)
    Arm/Group Description Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 3 1/2 years. Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 3 1/2 years. Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 3 1/2 years.
    Measure Participants 66 42 51
    Number (95% Confidence Interval) [Percentage of participants]
    92.4
    133.9%
    97.6
    232.4%
    94.1
    171.1%
    5. Secondary Outcome
    Title Percentage of Participants With Event-free Survival (EFS)
    Description Percentage of participants who were event free. Event Free Probability defined as time from randomization at study entry to first event (induction failure, induction death, relapse, second malignant neoplasm, remission death) or date of last contact for subjects who are event-free.
    Time Frame 5 Years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm I (Calaspargase Pegol 2100) Arm II (Calaspargase Pegol 2500) Arm III (Pegaspargase 2500)
    Arm/Group Description Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 3 1/2 years. Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 3 1/2 years. Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 3 1/2 years.
    Measure Participants 69 42 54
    Number (95% Confidence Interval) [Percentage of participants]
    72.35
    104.9%
    80.8
    192.4%
    79.34
    144.3%
    6. Secondary Outcome
    Title Asparaginase Level
    Description The proportion of patients with an asparaginase level of at least 0.1 IU/mL and the proportion with at least 0.4 IU/mL on Days 4, 15, 22 and 29 of Induction compared to Oncaspar
    Time Frame Days 4, 15, 22 and 29 of Induction

    Outcome Measure Data

    Analysis Population Description
    Patients who had data collected.
    Arm/Group Title Arm I (Calaspargase Pegol 2100) Arm II (Calaspargase Pegol 2500) Arm III (Pegaspargase 2500)
    Arm/Group Description Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 3 1/2 years. Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 3 1/2 years. Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 3 1/2 years.
    Measure Participants 69 42 54
    Level at least 0.1 IU/mL day 4
    0
    0
    0
    Level at least 0.1 IU/mL day 15
    98.4
    100
    100
    Level at least 0.1 IU/mL day 22
    98.2
    100
    95.1
    Level at least 0.1 IU/mL day 29
    94.9
    95.0
    28.6
    Level at least 0.4 IU/mL day 4
    0
    0
    0
    Level at least 0.4 IU/mL day 15
    75.8
    95.0
    93.0
    Level at least 0.4 IU/mL day 22
    37.5
    62.5
    14.6
    Level at least 0.4 IU/mL day 29
    13.6
    27.5
    0
    7. Secondary Outcome
    Title Plasma and CSF Concentrations of Asparagine in ug/ml
    Description The plasma and CSF concentrations of asparagine in ug/ml after administration of EZN-2285 compared to Oncaspar.
    Time Frame 25 Days Post-dose (Day 29)

    Outcome Measure Data

    Analysis Population Description
    Patients who had data collected.
    Arm/Group Title Arm I (Calaspargase Pegol 2100) Arm II (Calaspargase Pegol 2500) Arm III (Pegaspargase 2500)
    Arm/Group Description Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 3 1/2 years. Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 3 1/2 years. Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 3 1/2 years.
    Measure Participants 69 42 54
    CSF asparagine concentration (ug/mL)
    0.2
    (0.108)
    0.19
    (0.086)
    0.26
    (0.26)
    Plasma asparagine concentration (ug/mL)
    0.2
    (0.784)
    0.25
    (1.231)
    0.83
    (2.195)
    8. Secondary Outcome
    Title Immunogenicity
    Description Number of Patients with Positive Immunogenicity tests
    Time Frame 25 Days Post-dose (Day 29)

    Outcome Measure Data

    Analysis Population Description
    Patients who had data collected.
    Arm/Group Title Arm I (Calaspargase Pegol 2100) Arm II (Calaspargase Pegol 2500) Arm III (Pegaspargase 2500)
    Arm/Group Description Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 3 1/2 years. Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 3 1/2 years. Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 3 1/2 years.
    Measure Participants 69 42 54
    Count of Participants [Participants]
    2
    2.9%
    2
    4.8%
    4
    7.3%
    9. Secondary Outcome
    Title Toxicities During Post Induction Intensification Therapy (All Grades)
    Description The calculation of AE incidence will be based on the number of patients per AE category. For each patient who has multiple AEs classified to the same category, that patient will be tabulated under the worst toxicity grade for that AE category. The incidence of AEs will be tabulated by treatment arm and by organ class. Special attention will be paid to hypersensitivity, pancreatitis, coagulopathy, infection, neurologic dysfunction and thromboembolic events.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Patients who had data collected. International normalized ratio (INR). Activated partial thromboplastin (APT)
    Arm/Group Title Arm I (Calaspargase Pegol 2100) Arm II (Calaspargase Pegol 2500) Arm III (Pegaspargase 2500)
    Arm/Group Description Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 3 1/2 years. Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 3 1/2 years. Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 3 1/2 years.
    Measure Participants 49 33 43
    Alergic Reaction - Consolidation
    20.4
    29.6%
    27.3
    65%
    23.3
    42.4%
    Alergic Reaction - Delayed Intensification I
    4.4
    6.4%
    0.0
    0%
    0.0
    0%
    Alergic Reaction - Interim Maintenance I
    0.0
    0%
    0.0
    0%
    2.1
    3.8%
    CNS - Consolidation
    0.0
    0%
    0.0
    0%
    0.0
    0%
    CNS - Delayed Intensification I
    0.0
    0%
    3.8
    9%
    2.6
    4.7%
    CNS - Interim Maintenance I
    0.0
    0%
    0.0
    0%
    0.0
    0%
    Hyperbilirubinemia - Consolidation
    53.1
    77%
    45.5
    108.3%
    30.2
    54.9%
    Hyperbilirubinemia - Delayed Intensification I
    28.9
    41.9%
    38.5
    91.7%
    10.5
    19.1%
    Hyperbilirubinemia - Interim Maintenance I
    41.3
    59.9%
    27.6
    65.7%
    33.3
    60.5%
    Hyperglycemia - Consolidation
    44.9
    65.1%
    42.4
    101%
    46.5
    84.5%
    Hyperglycemia - Delayed Intensification I
    44.4
    64.3%
    61.5
    146.4%
    36.8
    66.9%
    Hyperglycemia - Interim Maintenance I
    34.8
    50.4%
    44.8
    106.7%
    33.3
    60.5%
    Hyperlipidemia - Consolidation
    2.0
    2.9%
    3.0
    7.1%
    7.0
    12.7%
    Hyperlipidemia - Delayed Intensification I
    2.2
    3.2%
    0.0
    0%
    0.0
    0%
    Hyperlipidemia - Interim Maintenance I
    2.2
    3.2%
    3.4
    8.1%
    2.6
    4.7%
    % patients w/INR increase - Consolidation
    6.1
    8.8%
    3.0
    7.1%
    7.0
    12.7%
    % pts w/INR increase - Delayed Intensification I
    6.7
    9.7%
    3.8
    9%
    0.0
    0%
    % patients w/INR increase - Interim Maintenance I
    2.2
    3.2%
    0.0
    0%
    2.6
    4.7%
    Pancreatitis - Consolidation
    10.2
    14.8%
    6.1
    14.5%
    7.0
    12.7%
    Pancreatitis -Delayed Intensification I
    2.2
    3.2%
    7.7
    18.3%
    0.0
    0%
    Pancreatitis - Interim Maintenance I
    2.2
    3.2%
    3.4
    8.1%
    2.6
    4.7%
    % pts w/prolongation of APT time - Consolidation
    8.2
    11.9%
    9.1
    21.7%
    7.0
    12.7%
    % pts w/prolongation APT time -Delayed Intension I
    8.9
    12.9%
    26.9
    64%
    18.4
    33.5%
    %pts w/prolongation APT time-Interim maintenance I
    6.5
    9.4%
    6.9
    16.4%
    7.7
    14%
    Thrombosis - Consolidation
    0.0
    0%
    0.0
    0%
    2.3
    4.2%
    Thrombosis - Delayed Intensification I
    2.2
    3.2%
    0.0
    0%
    0.0
    0%
    Thrombosis - Interim Maintenance I
    0.0
    0%
    0.0
    0%
    0.0
    0%
    10. Secondary Outcome
    Title Relationship Between PK and Presence of Antibodies
    Description Patients with presence of Antibodies.
    Time Frame Day 29 of consolidation

    Outcome Measure Data

    Analysis Population Description
    These data will never be collected.
    Arm/Group Title Arm I (Calaspargase Pegol 2100) Arm II (Calaspargase Pegol 2500) Arm III (Pegaspargase 2500)
    Arm/Group Description Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 3 1/2 years. Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 3 1/2 years. Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 3 1/2 years.
    Measure Participants 0 0 0

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Arm I (Calaspargase Pegol 2100) Arm II (Calaspargase Pegol 2500) Arm III (Pegaspargase 2500)
    Arm/Group Description calaspargase pegol 2100 calaspargase pegol 2500 pegaspargase 2500
    All Cause Mortality
    Arm I (Calaspargase Pegol 2100) Arm II (Calaspargase Pegol 2500) Arm III (Pegaspargase 2500)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Arm I (Calaspargase Pegol 2100) Arm II (Calaspargase Pegol 2500) Arm III (Pegaspargase 2500)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 54/69 (78.3%) 34/42 (81%) 32/54 (59.3%)
    Blood and lymphatic system disorders
    Anemia 1/69 (1.4%) 1 1/42 (2.4%) 1 1/54 (1.9%) 1
    Febrile neutropenia 1/69 (1.4%) 1 4/42 (9.5%) 4 2/54 (3.7%) 2
    Hemolysis 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Cardiac disorders
    Cardiac disorders - Other, specify 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Supraventricular tachycardia 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 11/69 (15.9%) 14 7/42 (16.7%) 7 4/54 (7.4%) 4
    Anal pain 2/69 (2.9%) 2 0/42 (0%) 0 0/54 (0%) 0
    Ascites 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Constipation 0/69 (0%) 0 0/42 (0%) 0 1/54 (1.9%) 1
    Duodenal perforation 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Mucositis oral 1/69 (1.4%) 1 1/42 (2.4%) 1 2/54 (3.7%) 2
    Nausea 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Oral pain 3/69 (4.3%) 5 0/42 (0%) 0 1/54 (1.9%) 1
    Pancreatic necrosis 1/69 (1.4%) 1 0/42 (0%) 0 1/54 (1.9%) 1
    Pancreatitis 8/69 (11.6%) 8 6/42 (14.3%) 6 4/54 (7.4%) 4
    Rectal pain 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Typhlitis 2/69 (2.9%) 2 0/42 (0%) 0 0/54 (0%) 0
    Vomiting 0/69 (0%) 0 2/42 (4.8%) 2 2/54 (3.7%) 2
    General disorders
    Death NOS 4/69 (5.8%) 4 1/42 (2.4%) 1 1/54 (1.9%) 1
    Fatigue 2/69 (2.9%) 2 0/42 (0%) 0 0/54 (0%) 0
    Fever 2/69 (2.9%) 2 0/42 (0%) 0 1/54 (1.9%) 1
    Irritability 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Pain 2/69 (2.9%) 2 2/42 (4.8%) 2 1/54 (1.9%) 2
    Hepatobiliary disorders
    Hepatobiliary disorders - Other, specify 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Immune system disorders
    Anaphylaxis 13/69 (18.8%) 13 11/42 (26.2%) 11 10/54 (18.5%) 11
    Infections and infestations
    Enterocolitis infectious 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Infections and infestations - Other, specify 14/69 (20.3%) 17 8/42 (19%) 10 4/54 (7.4%) 6
    Infective myositis 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Lung infection 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Sepsis 2/69 (2.9%) 2 1/42 (2.4%) 1 0/54 (0%) 0
    Urinary tract infection 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Investigations
    Activated partial thromboplastin time prolonged 3/69 (4.3%) 3 3/42 (7.1%) 3 3/54 (5.6%) 3
    Alanine aminotransferase increased 4/69 (5.8%) 4 2/42 (4.8%) 3 5/54 (9.3%) 6
    Aspartate aminotransferase increased 5/69 (7.2%) 5 2/42 (4.8%) 2 4/54 (7.4%) 4
    Blood bilirubin increased 12/69 (17.4%) 13 8/42 (19%) 10 10/54 (18.5%) 12
    CPK increased 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Cholesterol high 2/69 (2.9%) 4 2/42 (4.8%) 4 3/54 (5.6%) 5
    Creatinine increased 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Fibrinogen decreased 4/69 (5.8%) 4 3/42 (7.1%) 3 3/54 (5.6%) 3
    GGT increased 1/69 (1.4%) 1 2/42 (4.8%) 2 1/54 (1.9%) 1
    INR increased 1/69 (1.4%) 1 3/42 (7.1%) 3 0/54 (0%) 0
    Investigations - Other, specify 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Lipase increased 7/69 (10.1%) 7 4/42 (9.5%) 4 4/54 (7.4%) 4
    Lymphocyte count decreased 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Neutrophil count decreased 2/69 (2.9%) 2 0/42 (0%) 0 2/54 (3.7%) 2
    Platelet count decreased 6/69 (8.7%) 6 1/42 (2.4%) 1 1/54 (1.9%) 2
    Serum amylase increased 8/69 (11.6%) 8 1/42 (2.4%) 1 2/54 (3.7%) 2
    Weight loss 3/69 (4.3%) 3 2/42 (4.8%) 2 1/54 (1.9%) 7
    White blood cell decreased 1/69 (1.4%) 1 2/42 (4.8%) 2 1/54 (1.9%) 1
    Metabolism and nutrition disorders
    Acidosis 0/69 (0%) 0 2/42 (4.8%) 2 0/54 (0%) 0
    Anorexia 5/69 (7.2%) 7 1/42 (2.4%) 10 1/54 (1.9%) 7
    Dehydration 2/69 (2.9%) 3 1/42 (2.4%) 1 3/54 (5.6%) 4
    Glucose intolerance 2/69 (2.9%) 2 0/42 (0%) 0 1/54 (1.9%) 1
    Hyperglycemia 21/69 (30.4%) 27 14/42 (33.3%) 16 12/54 (22.2%) 17
    Hyperkalemia 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Hypertriglyceridemia 5/69 (7.2%) 7 4/42 (9.5%) 7 6/54 (11.1%) 10
    Hyperuricemia 0/69 (0%) 0 0/42 (0%) 0 1/54 (1.9%) 1
    Hypoalbuminemia 5/69 (7.2%) 6 2/42 (4.8%) 2 1/54 (1.9%) 1
    Hypocalcemia 3/69 (4.3%) 3 0/42 (0%) 0 2/54 (3.7%) 2
    Hypokalemia 4/69 (5.8%) 4 0/42 (0%) 0 0/54 (0%) 0
    Hyponatremia 3/69 (4.3%) 3 0/42 (0%) 0 0/54 (0%) 0
    Hypophosphatemia 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Tumor lysis syndrome 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Back pain 2/69 (2.9%) 2 0/42 (0%) 0 0/54 (0%) 0
    Chest wall pain 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Generalized muscle weakness 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Joint effusion 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Muscle weakness left-sided 0/69 (0%) 0 0/42 (0%) 0 1/54 (1.9%) 1
    Muscle weakness right-sided 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Musculoskeletal and connective tissue disorder - Other, specify 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Myalgia 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Myositis 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Pain in extremity 2/69 (2.9%) 2 0/42 (0%) 0 0/54 (0%) 0
    Nervous system disorders
    Arachnoiditis 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Ataxia 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Depressed level of consciousness 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Dizziness 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Dysphasia 2/69 (2.9%) 2 1/42 (2.4%) 2 0/54 (0%) 0
    Encephalopathy 2/69 (2.9%) 2 3/42 (7.1%) 3 1/54 (1.9%) 1
    Headache 2/69 (2.9%) 3 0/42 (0%) 0 1/54 (1.9%) 1
    Intracranial hemorrhage 1/69 (1.4%) 2 0/42 (0%) 0 0/54 (0%) 0
    Leukoencephalopathy 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Nervous system disorders - Other, specify 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Seizure 2/69 (2.9%) 2 2/42 (4.8%) 2 1/54 (1.9%) 1
    Syncope 2/69 (2.9%) 2 2/42 (4.8%) 2 3/54 (5.6%) 3
    Psychiatric disorders
    Agitation 2/69 (2.9%) 2 0/42 (0%) 0 0/54 (0%) 0
    Anxiety 1/69 (1.4%) 1 2/42 (4.8%) 2 0/54 (0%) 0
    Confusion 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Depression 2/69 (2.9%) 2 0/42 (0%) 0 0/54 (0%) 0
    Psychosis 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 2/69 (2.9%) 2 0/42 (0%) 0 2/54 (3.7%) 2
    Chronic kidney disease 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Adult respiratory distress syndrome 2/69 (2.9%) 2 0/42 (0%) 0 0/54 (0%) 0
    Cough 0/69 (0%) 0 0/42 (0%) 0 1/54 (1.9%) 1
    Dyspnea 3/69 (4.3%) 3 1/42 (2.4%) 1 1/54 (1.9%) 1
    Epistaxis 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Hypoxia 6/69 (8.7%) 6 3/42 (7.1%) 3 3/54 (5.6%) 3
    Pleural effusion 3/69 (4.3%) 3 0/42 (0%) 0 0/54 (0%) 0
    Respiratory, thoracic and mediastinal disorders - Other, specify 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Skin and subcutaneous tissue disorders
    Erythema multiforme 0/69 (0%) 0 0/42 (0%) 0 1/54 (1.9%) 1
    Purpura 1/69 (1.4%) 1 1/42 (2.4%) 1 0/54 (0%) 0
    Rash maculo-papular 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Vascular disorders
    Hematoma 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Hypertension 3/69 (4.3%) 3 0/42 (0%) 0 3/54 (5.6%) 3
    Hypotension 7/69 (10.1%) 7 1/42 (2.4%) 1 1/54 (1.9%) 1
    Thromboembolic event 5/69 (7.2%) 7 0/42 (0%) 0 1/54 (1.9%) 1
    Vascular disorders - Other, specify 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Other (Not Including Serious) Adverse Events
    Arm I (Calaspargase Pegol 2100) Arm II (Calaspargase Pegol 2500) Arm III (Pegaspargase 2500)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 64/69 (92.8%) 40/42 (95.2%) 51/54 (94.4%)
    Blood and lymphatic system disorders
    Anemia 18/69 (26.1%) 23 16/42 (38.1%) 27 23/54 (42.6%) 33
    Blood and lymphatic system disorders - Other, specify 1/69 (1.4%) 1 0/42 (0%) 0 1/54 (1.9%) 1
    Disseminated intravascular coagulation 1/69 (1.4%) 1 1/42 (2.4%) 1 0/54 (0%) 0
    Febrile neutropenia 37/69 (53.6%) 88 26/42 (61.9%) 60 31/54 (57.4%) 56
    Hemolysis 0/69 (0%) 0 0/42 (0%) 0 1/54 (1.9%) 1
    Cardiac disorders
    Left ventricular systolic dysfunction 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Sinus tachycardia 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Ear and labyrinth disorders
    Middle ear inflammation 1/69 (1.4%) 1 1/42 (2.4%) 1 0/54 (0%) 0
    Eye disorders
    Eye disorders - Other, specify 1/69 (1.4%) 2 0/42 (0%) 0 1/54 (1.9%) 1
    Retinal detachment 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Vitreous hemorrhage 0/69 (0%) 0 0/42 (0%) 0 1/54 (1.9%) 1
    Gastrointestinal disorders
    Abdominal pain 7/69 (10.1%) 7 8/42 (19%) 8 6/54 (11.1%) 9
    Anal pain 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Ascites 0/69 (0%) 0 0/42 (0%) 0 1/54 (1.9%) 1
    Colitis 1/69 (1.4%) 1 0/42 (0%) 0 1/54 (1.9%) 1
    Diarrhea 8/69 (11.6%) 10 4/42 (9.5%) 6 2/54 (3.7%) 2
    Enterocolitis 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Esophagitis 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Fecal incontinence 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Gastritis 0/69 (0%) 0 0/42 (0%) 0 1/54 (1.9%) 1
    Ileus 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Lower gastrointestinal hemorrhage 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Malabsorption 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Mucositis oral 16/69 (23.2%) 23 4/42 (9.5%) 5 7/54 (13%) 9
    Nausea 9/69 (13%) 10 3/42 (7.1%) 3 2/54 (3.7%) 3
    Oral hemorrhage 2/69 (2.9%) 2 0/42 (0%) 0 0/54 (0%) 0
    Oral pain 6/69 (8.7%) 7 1/42 (2.4%) 1 1/54 (1.9%) 1
    Pancreatitis 1/69 (1.4%) 1 2/42 (4.8%) 3 0/54 (0%) 0
    Vomiting 5/69 (7.2%) 7 2/42 (4.8%) 3 5/54 (9.3%) 5
    General disorders
    Facial pain 0/69 (0%) 0 0/42 (0%) 0 1/54 (1.9%) 1
    Fatigue 3/69 (4.3%) 4 3/42 (7.1%) 4 2/54 (3.7%) 2
    Fever 3/69 (4.3%) 4 5/42 (11.9%) 5 3/54 (5.6%) 3
    Irritability 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Multi-organ failure 0/69 (0%) 0 0/42 (0%) 0 1/54 (1.9%) 1
    Non-cardiac chest pain 2/69 (2.9%) 2 3/42 (7.1%) 3 2/54 (3.7%) 2
    Pain 5/69 (7.2%) 10 1/42 (2.4%) 1 2/54 (3.7%) 3
    Hepatobiliary disorders
    Cholecystitis 0/69 (0%) 0 0/42 (0%) 0 1/54 (1.9%) 1
    Immune system disorders
    Anaphylaxis 2/69 (2.9%) 2 2/42 (4.8%) 2 1/54 (1.9%) 1
    Infections and infestations
    Abdominal infection 0/69 (0%) 0 1/42 (2.4%) 1 1/54 (1.9%) 1
    Anorectal infection 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Bladder infection 0/69 (0%) 0 1/42 (2.4%) 1 1/54 (1.9%) 1
    Catheter related infection 2/69 (2.9%) 2 0/42 (0%) 0 1/54 (1.9%) 1
    Enterocolitis infectious 5/69 (7.2%) 6 1/42 (2.4%) 1 1/54 (1.9%) 2
    Infections and infestations - Other, specify 30/69 (43.5%) 57 23/42 (54.8%) 55 18/54 (33.3%) 39
    Infective myositis 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Lip infection 1/69 (1.4%) 2 0/42 (0%) 0 0/54 (0%) 0
    Lung infection 8/69 (11.6%) 9 3/42 (7.1%) 3 0/54 (0%) 0
    Mucosal infection 1/69 (1.4%) 1 0/42 (0%) 0 1/54 (1.9%) 1
    Otitis media 0/69 (0%) 0 0/42 (0%) 0 2/54 (3.7%) 2
    Pancreas infection 0/69 (0%) 0 0/42 (0%) 0 1/54 (1.9%) 1
    Paronychia 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Peripheral nerve infection 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Pharyngitis 2/69 (2.9%) 2 0/42 (0%) 0 0/54 (0%) 0
    Scrotal infection 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Sepsis 3/69 (4.3%) 3 0/42 (0%) 0 1/54 (1.9%) 1
    Sinusitis 1/69 (1.4%) 1 0/42 (0%) 0 2/54 (3.7%) 2
    Skin infection 3/69 (4.3%) 4 2/42 (4.8%) 2 2/54 (3.7%) 3
    Stoma site infection 0/69 (0%) 0 0/42 (0%) 0 1/54 (1.9%) 1
    Upper respiratory infection 3/69 (4.3%) 3 1/42 (2.4%) 1 1/54 (1.9%) 1
    Urinary tract infection 4/69 (5.8%) 5 2/42 (4.8%) 2 1/54 (1.9%) 1
    Wound infection 1/69 (1.4%) 1 1/42 (2.4%) 1 0/54 (0%) 0
    Injury, poisoning and procedural complications
    Injury, poisoning and procedural complications - Other, specify 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Tracheal obstruction 0/69 (0%) 0 0/42 (0%) 0 1/54 (1.9%) 1
    Vascular access complication 0/69 (0%) 0 0/42 (0%) 0 1/54 (1.9%) 1
    Wound dehiscence 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Investigations
    Activated partial thromboplastin time prolonged 1/69 (1.4%) 1 0/42 (0%) 0 1/54 (1.9%) 1
    Alanine aminotransferase increased 25/69 (36.2%) 71 22/42 (52.4%) 47 27/54 (50%) 73
    Alkaline phosphatase increased 3/69 (4.3%) 3 1/42 (2.4%) 1 0/54 (0%) 0
    Aspartate aminotransferase increased 10/69 (14.5%) 19 11/42 (26.2%) 15 14/54 (25.9%) 30
    Blood bilirubin increased 8/69 (11.6%) 8 3/42 (7.1%) 3 3/54 (5.6%) 3
    Cholesterol high 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Creatinine increased 2/69 (2.9%) 2 0/42 (0%) 0 1/54 (1.9%) 1
    GGT increased 3/69 (4.3%) 3 3/42 (7.1%) 7 7/54 (13%) 19
    Investigations - Other, specify 1/69 (1.4%) 1 1/42 (2.4%) 1 0/54 (0%) 0
    Lipase increased 2/69 (2.9%) 2 7/42 (16.7%) 8 5/54 (9.3%) 5
    Lymphocyte count decreased 0/69 (0%) 0 4/42 (9.5%) 4 0/54 (0%) 0
    Neutrophil count decreased 44/69 (63.8%) 121 29/42 (69%) 82 36/54 (66.7%) 92
    Platelet count decreased 30/69 (43.5%) 52 20/42 (47.6%) 37 22/54 (40.7%) 33
    Serum amylase increased 0/69 (0%) 0 2/42 (4.8%) 2 2/54 (3.7%) 2
    Weight gain 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Weight loss 5/69 (7.2%) 5 4/42 (9.5%) 5 1/54 (1.9%) 1
    White blood cell decreased 19/69 (27.5%) 27 16/42 (38.1%) 34 18/54 (33.3%) 45
    Metabolism and nutrition disorders
    Acidosis 2/69 (2.9%) 2 2/42 (4.8%) 2 2/54 (3.7%) 3
    Alkalosis 1/69 (1.4%) 1 0/42 (0%) 0 1/54 (1.9%) 1
    Anorexia 11/69 (15.9%) 13 8/42 (19%) 11 5/54 (9.3%) 5
    Dehydration 1/69 (1.4%) 1 5/42 (11.9%) 5 3/54 (5.6%) 5
    Glucose intolerance 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Hypercalcemia 2/69 (2.9%) 2 0/42 (0%) 0 0/54 (0%) 0
    Hyperglycemia 18/69 (26.1%) 36 11/42 (26.2%) 12 9/54 (16.7%) 18
    Hyperkalemia 9/69 (13%) 10 2/42 (4.8%) 3 3/54 (5.6%) 3
    Hypernatremia 0/69 (0%) 0 0/42 (0%) 0 1/54 (1.9%) 1
    Hyperuricemia 2/69 (2.9%) 2 4/42 (9.5%) 4 2/54 (3.7%) 2
    Hypoalbuminemia 8/69 (11.6%) 11 8/42 (19%) 9 2/54 (3.7%) 3
    Hypocalcemia 13/69 (18.8%) 18 4/42 (9.5%) 4 11/54 (20.4%) 15
    Hypoglycemia 0/69 (0%) 0 0/42 (0%) 0 3/54 (5.6%) 3
    Hypokalemia 25/69 (36.2%) 40 15/42 (35.7%) 18 14/54 (25.9%) 21
    Hypomagnesemia 0/69 (0%) 0 1/42 (2.4%) 1 2/54 (3.7%) 2
    Hyponatremia 12/69 (17.4%) 12 8/42 (19%) 10 8/54 (14.8%) 10
    Hypophosphatemia 9/69 (13%) 10 2/42 (4.8%) 2 3/54 (5.6%) 3
    Obesity 0/69 (0%) 0 1/42 (2.4%) 1 2/54 (3.7%) 7
    Tumor lysis syndrome 2/69 (2.9%) 2 5/42 (11.9%) 5 1/54 (1.9%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia 2/69 (2.9%) 2 1/42 (2.4%) 1 0/54 (0%) 0
    Avascular necrosis 2/69 (2.9%) 3 2/42 (4.8%) 2 2/54 (3.7%) 9
    Back pain 5/69 (7.2%) 5 3/42 (7.1%) 3 4/54 (7.4%) 4
    Bone pain 1/69 (1.4%) 1 1/42 (2.4%) 1 0/54 (0%) 0
    Generalized muscle weakness 3/69 (4.3%) 3 2/42 (4.8%) 3 0/54 (0%) 0
    Muscle weakness left-sided 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Muscle weakness lower limb 0/69 (0%) 0 0/42 (0%) 0 1/54 (1.9%) 1
    Myositis 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Neck pain 0/69 (0%) 0 0/42 (0%) 0 2/54 (3.7%) 2
    Pain in extremity 3/69 (4.3%) 5 4/42 (9.5%) 5 3/54 (5.6%) 3
    Nervous system disorders
    Abducens nerve disorder 1/69 (1.4%) 3 0/42 (0%) 0 0/54 (0%) 0
    Ataxia 0/69 (0%) 0 1/42 (2.4%) 1 1/54 (1.9%) 1
    Cerebrospinal fluid leakage 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Cognitive disturbance 0/69 (0%) 0 0/42 (0%) 0 1/54 (1.9%) 1
    Depressed level of consciousness 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Dizziness 0/69 (0%) 0 2/42 (4.8%) 2 2/54 (3.7%) 3
    Dysphasia 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Encephalopathy 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Headache 1/69 (1.4%) 1 7/42 (16.7%) 8 7/54 (13%) 7
    Hypoglossal nerve disorder 0/69 (0%) 0 0/42 (0%) 0 1/54 (1.9%) 1
    Intracranial hemorrhage 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Nervous system disorders - Other, specify 2/69 (2.9%) 2 0/42 (0%) 0 0/54 (0%) 0
    Neuralgia 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Seizure 1/69 (1.4%) 2 0/42 (0%) 0 0/54 (0%) 0
    Syncope 0/69 (0%) 0 1/42 (2.4%) 1 1/54 (1.9%) 1
    Tremor 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Vagus nerve disorder 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Vasovagal reaction 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Psychiatric disorders
    Agitation 1/69 (1.4%) 1 1/42 (2.4%) 1 1/54 (1.9%) 1
    Anxiety 1/69 (1.4%) 2 0/42 (0%) 0 2/54 (3.7%) 2
    Confusion 0/69 (0%) 0 0/42 (0%) 0 1/54 (1.9%) 1
    Depression 2/69 (2.9%) 2 2/42 (4.8%) 2 0/54 (0%) 0
    Insomnia 0/69 (0%) 0 1/42 (2.4%) 1 1/54 (1.9%) 1
    Personality change 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Psychiatric disorders - Other, specify 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Suicidal ideation 1/69 (1.4%) 2 0/42 (0%) 0 0/54 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Chronic kidney disease 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Reproductive system and breast disorders
    Perineal pain 0/69 (0%) 0 0/42 (0%) 0 1/54 (1.9%) 1
    Reproductive system and breast disorders - Other, specify 0/69 (0%) 0 0/42 (0%) 0 1/54 (1.9%) 1
    Uterine hemorrhage 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Adult respiratory distress syndrome 2/69 (2.9%) 2 1/42 (2.4%) 1 0/54 (0%) 0
    Apnea 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Dyspnea 2/69 (2.9%) 2 0/42 (0%) 0 1/54 (1.9%) 1
    Epistaxis 3/69 (4.3%) 5 1/42 (2.4%) 2 1/54 (1.9%) 1
    Hypoxia 8/69 (11.6%) 10 3/42 (7.1%) 3 5/54 (9.3%) 5
    Pharyngeal mucositis 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Pharyngolaryngeal pain 3/69 (4.3%) 3 0/42 (0%) 0 0/54 (0%) 0
    Pleural effusion 6/69 (8.7%) 7 0/42 (0%) 0 1/54 (1.9%) 1
    Pneumonitis 1/69 (1.4%) 1 1/42 (2.4%) 1 0/54 (0%) 0
    Respiratory, thoracic and mediastinal disorders - Other, specify 0/69 (0%) 0 1/42 (2.4%) 1 1/54 (1.9%) 1
    Skin and subcutaneous tissue disorders
    Pain of skin 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Pruritus 1/69 (1.4%) 1 1/42 (2.4%) 1 0/54 (0%) 0
    Purpura 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Rash maculo-papular 2/69 (2.9%) 2 0/42 (0%) 0 0/54 (0%) 0
    Skin and subcutaneous tissue disorders - Other, specify 0/69 (0%) 0 0/42 (0%) 0 1/54 (1.9%) 1
    Urticaria 0/69 (0%) 0 1/42 (2.4%) 1 0/54 (0%) 0
    Vascular disorders
    Capillary leak syndrome 0/69 (0%) 0 0/42 (0%) 0 1/54 (1.9%) 1
    Hematoma 1/69 (1.4%) 1 0/42 (0%) 0 0/54 (0%) 0
    Hypertension 3/69 (4.3%) 3 1/42 (2.4%) 1 1/54 (1.9%) 1
    Hypotension 4/69 (5.8%) 4 4/42 (9.5%) 5 3/54 (5.6%) 3
    Vascular disorders - Other, specify 2/69 (2.9%) 2 0/42 (0%) 0 0/54 (0%) 0

    Limitations/Caveats

    Data is not and never will be available for Outcome Measure 10, Relationship between PK and presence of antibodies.

    More Information

    Certain Agreements

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

    Must obtain sponsor approval.

    Results Point of Contact

    Name/Title Results Reporting Coordinator
    Organization Children's Oncology Group
    Phone 626-447-0064
    Email resultsreportingcoordinator@childrensoncologygroup.org
    Responsible Party:
    Children's Oncology Group
    ClinicalTrials.gov Identifier:
    NCT00671034
    Other Study ID Numbers:
    • AALL07P4
    • NCI-2009-00317
    • CDR0000594340
    • 08-606
    • COG-AALL07P4
    • AALL07P4
    • AALL07P4
    • U10CA098543
    First Posted:
    May 2, 2008
    Last Update Posted:
    Apr 27, 2021
    Last Verified:
    Apr 1, 2021