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

April 2, 2021 updated by: Children's Oncology Group

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. 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:

I. 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.

II. 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.

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

IV. 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.

V. 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.

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

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

VIII. 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.

IX. 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 Type

Interventional

Enrollment (Actual)

166

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham Cancer Center
    • California
      • Orange, California, United States, 92868
        • Children's Hospital of Orange County
      • Palo Alto, California, United States, 94304
        • Lucile Packard Children's Hospital Stanford University
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado
    • Connecticut
      • Farmington, Connecticut, United States, 06030
        • University of Connecticut
      • Hartford, Connecticut, United States, 06106
        • Connecticut Children's Medical Center
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Children's National Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Lurie Children's Hospital-Chicago
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University/Melvin and Bren Simon Cancer Center
      • Indianapolis, Indiana, United States, 46202
        • Riley Hospital for Children
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University/Sidney Kimmel Cancer Center
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Wayne State University/Karmanos Cancer Institute
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Children's Hospitals and Clinics of Minnesota - Minneapolis
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota/Masonic Cancer Center
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • New Mexico
      • Albuquerque, New Mexico, United States, 87102
        • University of New Mexico Cancer Center
    • New York
      • New York, New York, United States, 10016
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh of UPMC
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University/Ingram Cancer Center
    • Texas
      • Dallas, Texas, United States, 75390
        • UT Southwestern/Simmons Cancer Center-Dallas
    • Utah
      • Salt Lake City, Utah, United States, 84113
        • Primary Children's Hospital
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 30 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / 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.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
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: Cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • CTX
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamide Monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Drug: Mercaptopurine
Given PO
Other Names:
  • 6-MP
  • Purinethol
  • 3H-Purine-6-thiol
  • 6 MP
  • 6 Thiohypoxanthine
  • 6 Thiopurine
  • 6-Mercaptopurine
  • 6-Mercaptopurine Monohydrate
  • 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
  • U-4748
  • WR-2785
Drug: Vincristine Sulfate
Given IV
Other Names:
  • Oncovin
  • Kyocristine
  • Leurocristine Sulfate
  • Leurocristine, sulfate
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate
Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
  • Adriamycin
  • 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 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: Dexamethasone
Given PO or IV
Other Names:
  • Decadron
  • 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 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: 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
Drug: Thioguanine
Given PO
Other Names:
  • 6-TG
  • 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
  • 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: 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: Prednisone
Given IV or PO
Other Names:
  • Deltasone
  • Orasone
  • .delta.1-Cortisone
  • 1, 2-Dehydrocortisone
  • Adasone
  • Cortancyl
  • Dacortin
  • DeCortin
  • Decortisyl
  • Decorton
  • Delta 1-Cortisone
  • Delta-Dome
  • Deltacortene
  • Deltacortisone
  • Deltadehydrocortisone
  • Deltison
  • Deltra
  • Econosone
  • Lisacort
  • Meprosona-F
  • Metacortandracin
  • Meticorten
  • Ofisolona
  • Panafcort
  • Panasol-S
  • Paracort
  • Perrigo Prednisone
  • PRED
  • Predicor
  • Predicorten
  • Prednicen-M
  • Prednicort
  • Prednidib
  • Prednilonga
  • Predniment
  • Prednisone Intensol
  • Prednisonum
  • Prednitone
  • Promifen
  • Rayos
  • Servisone
  • SK-Prednisone
Drug: Methotrexate
Given IV, IT, or PO
Other Names:
  • Abitrexate
  • Folex
  • Mexate
  • MTX
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate-AQ
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039
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
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
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.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
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: Cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • CTX
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamide Monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Drug: Mercaptopurine
Given PO
Other Names:
  • 6-MP
  • Purinethol
  • 3H-Purine-6-thiol
  • 6 MP
  • 6 Thiohypoxanthine
  • 6 Thiopurine
  • 6-Mercaptopurine
  • 6-Mercaptopurine Monohydrate
  • 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
  • U-4748
  • WR-2785
Drug: Vincristine Sulfate
Given IV
Other Names:
  • Oncovin
  • Kyocristine
  • Leurocristine Sulfate
  • Leurocristine, sulfate
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate
Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
  • Adriamycin
  • 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 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: Dexamethasone
Given PO or IV
Other Names:
  • Decadron
  • 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 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: 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
Drug: Thioguanine
Given PO
Other Names:
  • 6-TG
  • 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
  • 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: Prednisone
Given IV or PO
Other Names:
  • Deltasone
  • Orasone
  • .delta.1-Cortisone
  • 1, 2-Dehydrocortisone
  • Adasone
  • Cortancyl
  • Dacortin
  • DeCortin
  • Decortisyl
  • Decorton
  • Delta 1-Cortisone
  • Delta-Dome
  • Deltacortene
  • Deltacortisone
  • Deltadehydrocortisone
  • Deltison
  • Deltra
  • Econosone
  • Lisacort
  • Meprosona-F
  • Metacortandracin
  • Meticorten
  • Ofisolona
  • Panafcort
  • Panasol-S
  • Paracort
  • Perrigo Prednisone
  • PRED
  • Predicor
  • Predicorten
  • Prednicen-M
  • Prednicort
  • Prednidib
  • Prednilonga
  • Predniment
  • Prednisone Intensol
  • Prednisonum
  • Prednitone
  • Promifen
  • Rayos
  • Servisone
  • SK-Prednisone
Drug: Methotrexate
Given IV, IT, or PO
Other Names:
  • Abitrexate
  • Folex
  • Mexate
  • MTX
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate-AQ
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039
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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetics (PK) (Half-life of SC-PEG E. Coli L-asparaginase (EZN-2285) Compared to Pegaspargase During Induction and Consolidation Therapy)
Time Frame: 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.
Post Day 29 of Induction and Post Day 22 of Consolidation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacodynamics (PD)
Time Frame: Day 29 of consolidation and induction
Plasma Asparaginase Concentration During consolidation and induction.
Day 29 of consolidation and induction
Percentage of Participants With Minimal Residual Disease (MRD)<0.01% at the End of Induction
Time Frame: End of induction (Day 29)
Percentage of participants with Negative MRD (MRD<0.01%).
End of induction (Day 29)
Percentage of Participants With Complete Remission at the End of Induction
Time Frame: End of induction (Day 29)
Complete Remission (CR) rate; where CR is defined as M1 marrow (< 5% lymphoblasts in the bone marrow)
End of induction (Day 29)
Percentage of Participants With Event-free Survival (EFS)
Time Frame: 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 Years
Asparaginase Level
Time Frame: 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
Days 4, 15, 22 and 29 of Induction
Plasma and CSF Concentrations of Asparagine in ug/ml
Time Frame: 25 Days Post-dose (Day 29)
The plasma and CSF concentrations of asparagine in ug/ml after administration of EZN-2285 compared to Oncaspar.
25 Days Post-dose (Day 29)
Immunogenicity
Time Frame: 25 Days Post-dose (Day 29)
Number of Patients with Positive Immunogenicity tests
25 Days Post-dose (Day 29)
Toxicities During Post Induction Intensification Therapy (All Grades)
Time Frame: 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.
Up to 5 years
Relationship Between PK and Presence of Antibodies
Time Frame: Day 29 of consolidation
Patients with presence of Antibodies.
Day 29 of consolidation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

July 21, 2008

Primary Completion (ACTUAL)

February 1, 2011

Study Completion (ACTUAL)

March 31, 2021

Study Registration Dates

First Submitted

May 1, 2008

First Submitted That Met QC Criteria

May 1, 2008

First Posted (ESTIMATE)

May 2, 2008

Study Record Updates

Last Update Posted (ACTUAL)

April 27, 2021

Last Update Submitted That Met QC Criteria

April 2, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AALL07P4 (OTHER: CTEP)
  • U10CA098543 (U.S. NIH Grant/Contract)
  • NCI-2009-00317 (REGISTRY: CTRP (Clinical Trial Reporting Program))
  • CDR0000594340
  • 08-606
  • COG-AALL07P4

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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