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Chemoimmunotherapy With Epratuzumab in Relapsed Acute Lymphoblastic Leukemia (ALL)

Sponsor
Children's Oncology Group (Other)
Overall Status
Completed
CT.gov ID
NCT00098839
Collaborator
National Cancer Institute (NCI) (NIH)
134
Enrollment
46
Locations
2
Arms
73.9
Duration (Months)
2.9
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This Phase II trial is studying how well giving epratuzumab together with an established chemotherapy platform works in treating young patients with relapsed acute lymphoblastic leukemia. Monoclonal antibodies, such as epratuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing them or by stopping them from dividing. Giving monoclonal antibody therapy in combination chemotherapy may kill cancer cells more effectively.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:

  1. Determine the feasibility of epratuzumab administered alone and in combination with re-induction combination chemotherapy in pediatric patients with relapsed CD22-positive acute lymphoblastic leukemia.

  2. Determine the toxic effects of this regimen in these patients.

  3. Determine the antitumor activity of this regimen in these patients.

  4. To estimate the remission re-induction rate and four-month event-free survival (EFS) for patients with early first relapse ALL who receive epratuzumab in combination with cytotoxic thermotherapy.

SECONDARY OBJECTIVES:

  1. Determine the pharmacokinetics of epratuzumab in these patients. II. Determine the biologic activity of epratuzumab using measurements of minimal residual disease in these patients.

  2. Determine the human anti-human antibody (HAHA) response in patients treated with this regimen.

OUTLINE: This is a multicenter study comprising a feasibility part A (closed to accrual as of 10/30/06) followed by a pilot part B study. A Simon's two stage design was initially used to evaluate the efficacy of the once weekly dosing schedule for part B patients (called B1 cohort), which planned to accrue a total of 112 patients with 56 to be enrolled at the first stage. After completion the accrual of stage 1, i.e. after 56 patients were enrolled, the design of part B was revised to evaluate a modified doing schedule (twice weekly doing, called B2 cohort) using a stratified two-stage design by London and Chang (2005), where patients enrolled to B2 were stratified according to relapse (first early marrow relapsed occurring < 18 months from initial diagnosis vs 18-36 months from initial diagnosis).

PART A (CLOSED TO ACCRUAL 10/30/06):

REDUCTION THERAPY: Patients receive epratuzumab IV over several hours on days -14, -10, -6, and -2 and cytarabine intrathecally (IT) on day -14*.

NOTE: *Patients who receive IT chemotherapy within 7 days of study entry as prior maintenance chemotherapy (e.g., before the diagnosis of relapse) did not receive this first dose of IT cytarabine.

RE-INDUCTION THERAPY (BLOCK 1): Patients received vincristine IV on days 1, 8, 15, and 22; oral prednisone two or three times daily on days 1-29; pegaspargase intramuscularly (IM) on days 2, 9, 16, and 23; dexrazoxane IV followed by doxorubicin IV over 15 minutes on day 1; methotrexate IT on days 15 and 29 for CNS-negative disease; and epratuzumab IV over 1 hour on days 8, 15, 22, and 29. Patients with CNS-positive disease also received triple IT therapy (ITT) consisting of methotrexate, cytarabine, hydrocortisone on days -10, -6, 1 and 15.

RE-INDUCTION THERAPY (BLOCK 2): Beginning at least 7 days after the last dose of IT chemotherapy, patients received etoposide IV over 2 hours and cyclophosphamide IV over 30 minutes on days 1-5. Patients also received high-dose methotrexate IV continuously over 24 hours on day 22. Beginning 42 hours after the start of the methotrexate infusion (day 24), patients received leucovorin calcium IV every 6 hours for a minimum of 3 doses. Patients with CNS-negative disease also receive methotrexate IT on days 1 and 22. Patients with CNS-positive disease will receive triple IT as in re-induction therapy (block 1) on days 1 and 22. Patients received filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 6 and continuing until blood counts recover.

RE-INDUCTION THERAPY (PART 3): Beginning at least 7 days after the last dose of IT chemotherapy, patients received cytarabine IV over 3 hours twice daily on days 1, 2, 8, and 9 and native E. Coli asparaginase IM on days 2 and 9. Patients receive G-CSF SC once daily beginning on day 10 and continuing until blood counts recovered.

PART B:

RE-INDUCTION THERAPY (BLOCK 1): Patients received vincristine, prednisone, pegaspargase, doxorubicin, cytarabine, methotrexate, and epratuzumab as in phase I re-induction therapy (block 1). Epratuzumab was given on Days 1, 8, 15 and 22 before amendment 5 (B1 cohort) and on Days 1, 4, 8, 11, 15, 18, 22 and 25 after amendment 5 (B2 cohort) Patients with CNS-negative disease received methotrexate IT on days 1 and 22. Patients with CNS-positive disease received triple IT therapy comprising methotrexate, cytarabine, and hydrocortisone on days 8, 15, 22, and 29.

RE-INDUCTION THERAPY (BLOCKS 2 AND 3): Patients received re-induction therapy blocks 2 and 3 as in the part A re-induction therapy (blocks 2 and 3) portion of the study.

Patients are followed annually.

Study Design

Study Type:
Interventional
Actual Enrollment :
134 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Feasibility Pilot and Phase II Study Of Chemoimmunotherapy With Epratuzumab (IND #12034) for Children With Relapsed CD22-Positive Acute Lymphoblastic Leukemia (ALL)
Study Start Date :
Feb 1, 2005
Actual Primary Completion Date :
Apr 1, 2011
Study Completion Date :
Apr 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Experimental: Reinduction Chemoimmunotherapy with Epratuzumab once weekly

Four weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 8, 15, 22. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, high-dose (HD) methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), Intrathecal triple therapy (ITT) (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy.

Drug: L-asparaginase
Given IM
Other Names:
  • ASNase
  • Colaspase
  • Crasnitin
  • Elspar
  • L-ASP

    • Drug: doxorubicin hydrochloride
    Given IV
    Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF

    • Drug: therapeutic hydrocortisone
    40 mg/m2/day PO divided BID or TID
    Other Names:
  • Aeroseb-HC
  • Barseb HC
  • Cetacort
  • Cort-Dome
  • Cortef

    • Drug: vincristine sulfate
    Given IV
    Other Names:
  • liposomal vincristine
  • Marqibo
  • vincristine liposomal
  • vincristine sulfate liposome injection

    • Biological: epratuzumab
    Given IV
    Other Names:
  • AMG 412
  • LL2
  • MOAB LL2
  • monoclonal antibody LL2

    • Drug: cytarabine
    Given IT
    Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside

    • Drug: prednisone
    Given orally
    Other Names:
  • DeCortin
  • Deltra

    • Drug: pegaspargase
    Given IM
    Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase

    • Drug: dexrazoxane hydrochloride
    Given IV
    Other Names:
  • Cardioxane
  • Savene
  • Totect
  • Zinecard

    • Drug: methotrexate
    Given IT
    Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX

    • Drug: etoposide
    Given IV
    Other Names:
  • EPEG
  • VP-16
  • VP-16-213

    • Drug: cyclophosphamide
    Given IV
    Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana

    • Drug: leucovorin calcium
    Given IV
    Other Names:
  • CF
  • CFR
  • LV

    • Biological: filgrastim
    Given SC
    Other Names:
  • G-CSF
  • Neupogen

    		•
    Experimental: Reinduction Chemoimmunotherapy with Epratuzumab twice weekly

    Eight 8 twice-weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 4, 8, 11, 15, 18, 22 & 25. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, high-dose (HD) methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), Intrathecal triple therapy (ITT) (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy.

    Drug: L-asparaginase
    Given IM
    Other Names:
  • ASNase
  • Colaspase
  • Crasnitin
  • Elspar
  • L-ASP

    • Drug: doxorubicin hydrochloride
    Given IV
    Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF

    • Drug: therapeutic hydrocortisone
    40 mg/m2/day PO divided BID or TID
    Other Names:
  • Aeroseb-HC
  • Barseb HC
  • Cetacort
  • Cort-Dome
  • Cortef

    • Drug: vincristine sulfate
    Given IV
    Other Names:
  • liposomal vincristine
  • Marqibo
  • vincristine liposomal
  • vincristine sulfate liposome injection

    • Biological: epratuzumab
    Given IV
    Other Names:
  • AMG 412
  • LL2
  • MOAB LL2
  • monoclonal antibody LL2

    • Drug: cytarabine
    Given IT
    Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside

    • Drug: prednisone
    Given orally
    Other Names:
  • DeCortin
  • Deltra

    • Drug: pegaspargase
    Given IM
    Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase

    • Drug: dexrazoxane hydrochloride
    Given IV
    Other Names:
  • Cardioxane
  • Savene
  • Totect
  • Zinecard

    • Drug: methotrexate
    Given IT
    Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX

    • Drug: etoposide
    Given IV
    Other Names:
  • EPEG
  • VP-16
  • VP-16-213

    • Drug: cyclophosphamide
    Given IV
    Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana

    • Drug: leucovorin calcium
    Given IV
    Other Names:
  • CF
  • CFR
  • LV

    • Biological: filgrastim
    Given SC
    Other Names:
  • G-CSF
  • Neupogen

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Remission Re-induction (CR2) Rate [At the end of Block 1 of re-induction therapy (day 36)]

      The proportion of patients who achieved complete response at the end Block 1 of re-induction therapy. Complete Remission (CR) - Attainment of M1 bone marrow (<5% blasts) with no evidence of circulating blasts or extramedullary disease and with recovery of peripheral counts (ANC >1000/uL and platelet count >100,000/uL). Partial Remission (PR) - Complete disappearance of circulating blasts and achievement of M2 marrow status (5% or < 25% blast cells and adequate cellularity). Partial Remission Cytolytic (PRCL) - Complete disappearance of circulating blasts and achievement of at least 50% reduction from baseline in bone marrow blast count. Minimal Response Cytolytic (MRCL) - 50% reduction in the peripheral blast count with no increase in peripheral white blood cell count.

    2. Event-free Survival Rate [At 4 months after enrollment]

      Proportion of patients who were event free at 4 months

    3. Rate of Minimal Residual Disease (MRD) < 0.01% [At the end of Block 1 of re-induction therapy (day 36)]

      Proportion of patients (evaluable and had MRD measured at the end of Block 1) who had MRD < 0.01%.

    Secondary Outcome Measures

    1. Pharmacokinetics [Up to day 36]

      Mean trough serum concentration measured before final dose of epratuzumab.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    2 Years to 31 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Diagnosis of B lymphoblastic leukemia (B-ALL)

    • At least 25% expression of CD22 by immunophenotyping

    • In marrow relapse (M3 bone marrow) with or without associated extramedullary disease as defined by 1 of the following:

    • In first or later marrow relapse occurring any time after initial diagnosis (part A [closed to accrual as of 10/30/06] or B)

    • In first, early marrow relapse with or without associated extramedullary disease occurring < 36 months from the time of initial diagnosis (part B only)

    • No B-cell L3 morphology OR evidence of a regulator gene that codes for a transcription factor (MYC) translocation by molecular or cytogenetic analysis

    • No Down syndrome

    • Patients with CNS or other extramedullary site involvement are allowed

    • Performance status - Karnofsky 50-100% (for patients > 10 years of age)

    • Performance status - Lansky 50-100% (for patients ≤ 10 years of age)

    • White Blood Count (WBC) ≤ 50,000/mm^3 (part A only [closed to accrual as of 10/30/06])

    • Bilirubin ≤ 1.5 times upper limit of normal unless disease-related (ULN)

    • Alanine aminotransferase (ALT) ≤ 5 times ULN

    • Albumin ≥ 2 g/dL

    • Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min

    • Creatinine as defined by age as follows:

    • ≤ 0.5 mg/dL (for patients < 1 year old)

    • ≤ 0.8 mg/dL (for patients 1 to 5 years old)

    • ≤ 1.0 mg/dL (for patients 6 to 10 years old)

    • ≤ 1.2 mg/dL (for patients 11 to 15 years old)

    • ≤ 1.5 mg/dL (for patients > 15 years old)

    • Shortening fraction ≥ 27% by echocardiogram

    • Ejection fraction ≥ 45% by Multi Gated Acquisition Scan (MUGA)

    • No dyspnea at rest

    • No exercise intolerance

    • Pulse oximetry > 94%

    • No active or uncontrolled infection

    • Not pregnant or nursing

    • Negative pregnancy test

    • Fertile patients must use effective contraception

    • Recovered from prior immunotherapy

    • At least 4 months since prior stem cell transplantation or rescue AND no evidence of active graft-vs-host disease

    • At least 7 days since prior hematopoietic growth factors

    • At least 7 days since prior biologic therapy*

    • No other concurrent immunotherapy

    • No other concurrent biologic therapy

    • Recovered from prior chemotherapy

    • No waiting period for children who relapse while receiving standard ALL maintenance therapy

    • No prior cumulative anthracycline exposure > 400 mg/m^2*

    • No concurrent chemotherapy

    • Recovered from prior radiotherapy

    • No concurrent radiotherapy

    • At least 2 days since prior hydroxyurea

    • No other concurrent investigational drugs

    • No other concurrent anticancer agents

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Birmingham Alabama United States 35294
    2 University of California San Francisco Medical Center-Parnassus Frisco California United States 94143
    3 Loma Linda University Medical Center Loma Linda California United States 92354
    4 Miller Children's Hospital Long Beach California United States 90806
    5 Children's Hospital Los Angeles Los Angeles California United States 90027
    6 David Geffen School of Medicine at UCLA Los Angeles California United States 90095
    7 Children's Hospital Central California Madera California United States 93636-8762
    8 Kaiser Permanente-Oakland Oakland California United States 94611
    9 Childrens Hospital of Orange County Orange California United States 92868-3874
    10 Lucile Packard Children's Hospital Stanford University Palo Alto California United States 94304
    11 Children's Hospital Colorado Aurora Colorado United States 80045
    12 Children's National Medical Center Washington District of Columbia United States 20010
    13 Saint Joseph Children's Hospital of Tampa Tampa Florida United States 33607
    14 Children's Healthcare of Atlanta - Egleston Atlanta Georgia United States 30322
    15 Indiana University Medical Center Indianapolis Indiana United States 46202
    16 University of Kentucky Lexington Kentucky United States 40536
    17 Tulane University Health Sciences Center New Orleans Louisiana United States 70112
    18 Eastern Maine Medical Center Bangor Maine United States 04401
    19 Johns Hopkins University Baltimore Maryland United States 21287-8936
    20 Dana-Farber Cancer Institute Boston Massachusetts United States 02115
    21 C S Mott Children's Hospital Ann Arbor Michigan United States 48109
    22 Wayne State University Detroit Michigan United States 48202
    23 University of Minnesota Medical Center-Fairview Minneapolis Minnesota United States 55455
    24 Mayo Clinic Rochester Minnesota United States 55905
    25 University of Mississippi Medical Center Jackson Mississippi United States 39216
    26 The Childrens Mercy Hospital Kansas City Missouri United States 64108
    27 UMDNJ - Robert Wood Johnson University Hospital New Brunswick New Jersey United States 08903
    28 Newark Beth Israel Medical Center Newark New Jersey United States 07112
    29 University of New Mexico Cancer Center Albuquerque New Mexico United States 87106
    30 New York University Langone Medical Center New York New York United States 10016
    31 Columbia University Medical Center New York New York United States 10032
    32 University of Rochester Rochester New York United States 14642
    33 Nationwide Children's Hospital Columbus Ohio United States 43205
    34 Oregon Health and Science University Portland Oregon United States 97239
    35 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    36 Medical University of South Carolina Charleston South Carolina United States 29425
    37 Vanderbilt-Ingram Cancer Center Nashville Tennessee United States 37232
    38 Baylor College of Medicine Houston Texas United States 77030
    39 M D Anderson Cancer Center Houston Texas United States 77030
    40 Primary Children's Medical Center Salt Lake City Utah United States 84113
    41 Seattle Children's Hospital Seattle Washington United States 98105
    42 Midwest Children's Cancer Center Milwaukee Wisconsin United States 53226
    43 The Children's Hospital at Westmead Sydney New South Wales Australia 2145
    44 Princess Margaret Hospital for Children Perth Western Australia Australia 6008
    45 Hospital Sainte-Justine Montreal Quebec Canada H3T 1C5
    46 San Jorge Children's Hospital Santurce Puerto Rico 00912

    Sponsors and Collaborators

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

    Investigators

    • Principal Investigator: Elizabeth Raetz, MD, Children's Oncology Group

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Children's Oncology Group
    ClinicalTrials.gov Identifier:
    NCT00098839
    Other Study ID Numbers:
    • ADVL04P2
    • NCI-2011-01624
    • COG-ADVL04P2
    • CDR0000396777
    • U10CA098543
    First Posted:
    Dec 9, 2004
    Last Update Posted:
    Dec 12, 2017
    Last Verified:
    Nov 1, 2017
    Additional relevant MeSH terms:
    Leukemia
    Precursor Cell Lymphoblastic Leukemia-Lymphoma
    Leukemia, Lymphoid
    Leucovorin
    Cytarabine
    Prednisone
    Hydrocortisone
    Hydrocortisone 17-butyrate 21-propionate
    Hydrocortisone acetate
    Hydrocortisone hemisuccinate
    Cyclophosphamide
    Doxorubicin
    Liposomal doxorubicin
    Methotrexate
    Etoposide
    Vincristine
    Etoposide phosphate
    Asparaginase
    Pegaspargase
    Epratuzumab
    Dexrazoxane
    Razoxane
    Levoleucovorin

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail The phase I part of the study was completed as of August 2006. The study was amended on 11/10/2006 and Part B (phase 2 pilot) was opened on 01/08/2007 which consisted of two dosing schedules for epratuzumab: weekly for four doses during Block 1 and twice weekly for eight doses during Block 1. This report is limited to Part B (116 enrollments).
    Arm/Group Title Reinduction Chemoimmunotherapy With Epratuzumab Once Weekly Reinduction Chemoimmunotherapy With Epratuzumab Twice Weekly
    Arm/Group Description Four weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 8, 15, 22. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, high-dose (HD) methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), Intrathecal triple therapy (ITT) (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC Eight 8 twice-weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 4, 8, 11, 15, 18, 22 & 25. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, high-dose (HD) methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), Intrathecal triple therapy (ITT) (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC
    Period Title: Overall Study
    STARTED 56 60
    COMPLETED 24 27
    NOT COMPLETED 32 33

    Baseline Characteristics

    Arm/Group Title Reinduction Chemoimmunotherapy With Epratuzumab Once Weekly Reinduction Chemoimmunotherapy With Epratuzumab Twice Weekly Total
    Arm/Group Description Four weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 8, 15, 22. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, HD methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), ITT (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC Eight 8 twice-weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 4, 8, 11, 15, 18, 22 & 25. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, HD methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), ITT (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC Total of all reporting groups
    Overall Participants 54 60 114
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    10.5
    (5.54)
    9.7
    (5.44)
    10.1
    (5.48)
    Age (Count of Participants)
    <=18 years
    48
    88.9%
    55
    91.7%
    103
    90.4%
    Between 18 and 65 years
    6
    11.1%
    5
    8.3%
    11
    9.6%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    23
    42.6%
    29
    48.3%
    52
    45.6%
    Male
    31
    57.4%
    31
    51.7%
    62
    54.4%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    3
    5%
    3
    2.6%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    10
    18.5%
    6
    10%
    16
    14%
    White
    38
    70.4%
    46
    76.7%
    84
    73.7%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    6
    11.1%
    5
    8.3%
    11
    9.6%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    14
    25.9%
    20
    33.3%
    34
    29.8%
    Not Hispanic or Latino
    37
    68.5%
    38
    63.3%
    75
    65.8%
    Unknown or Not Reported
    3
    5.6%
    2
    3.3%
    5
    4.4%

    Outcome Measures

    1. Primary Outcome
    Title Remission Re-induction (CR2) Rate
    Description The proportion of patients who achieved complete response at the end Block 1 of re-induction therapy. Complete Remission (CR) - Attainment of M1 bone marrow (<5% blasts) with no evidence of circulating blasts or extramedullary disease and with recovery of peripheral counts (ANC >1000/uL and platelet count >100,000/uL). Partial Remission (PR) - Complete disappearance of circulating blasts and achievement of M2 marrow status (5% or < 25% blast cells and adequate cellularity). Partial Remission Cytolytic (PRCL) - Complete disappearance of circulating blasts and achievement of at least 50% reduction from baseline in bone marrow blast count. Minimal Response Cytolytic (MRCL) - 50% reduction in the peripheral blast count with no increase in peripheral white blood cell count.
    Time Frame At the end of Block 1 of re-induction therapy (day 36)

    Outcome Measure Data

    Analysis Population Description
    Evaluable patients at the end of Block 1. There were 2 ineligible patients for once weekly arm and 6 patients not evaluable at the end of block 1 re-induction therapy. There were 10 patients for twice weekly arm not evaluable at the end of block 1 re-induction therapy.
    Arm/Group Title Reinduction Chemoimmunotherapy With Epratuzumab Once Weekly Reinduction Chemoimmunotherapy With Epratuzumab Twice Weekly
    Arm/Group Description Four weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 8, 15, 22. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, HD methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), ITT (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC Eight 8 twice-weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 4, 8, 11, 15, 18, 22 & 25. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, HD methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), ITT (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC
    Measure Participants 48 50
    Number [proportion of participants]
    .646
    1.2%
    .660
    1.1%
    2. Primary Outcome
    Title Event-free Survival Rate
    Description Proportion of patients who were event free at 4 months
    Time Frame At 4 months after enrollment

    Outcome Measure Data

    Analysis Population Description
    Evaluable patients at the end of Block 1. There were 2 ineligible patients for once weekly arm and 6 patients not evaluable at the end of block 1 re-induction therapy. There were 10 patients for twice weekly arm not evaluable at the end of block 1 re-induction therapy.
    Arm/Group Title Reinduction Chemoimmunotherapy With Epratuzumab Once Weekly Reinduction Chemoimmunotherapy With Epratuzumab Twice Weekly
    Arm/Group Description Four weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 8, 15, 22. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, HD methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), ITT (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC Eight 8 twice-weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 4, 8, 11, 15, 18, 22 & 25. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, HD methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), ITT (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC
    Measure Participants 48 50
    Number [Proportion of participants]
    .604
    1.1%
    .640
    1.1%
    3. Primary Outcome
    Title Rate of Minimal Residual Disease (MRD) < 0.01%
    Description Proportion of patients (evaluable and had MRD measured at the end of Block 1) who had MRD < 0.01%.
    Time Frame At the end of Block 1 of re-induction therapy (day 36)

    Outcome Measure Data

    Analysis Population Description
    Evaluable patients who had MRD measured at the end of Block 1. There were 2 ineligible patients for once weekly arm and 13 patients where MRD was not measured at the end of block 1 re-induction therapy. There were 16 patients for twice weekly arm where MRD was not measured at the end of block 1 re-induction therapy.
    Arm/Group Title Reinduction Chemoimmunotherapy With Epratuzumab Once Weekly Reinduction Chemoimmunotherapy With Epratuzumab Twice Weekly
    Arm/Group Description Four weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 8, 15, 22. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, HD methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), ITT (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC Eight 8 twice-weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 4, 8, 11, 15, 18, 22 & 25. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, HD methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), ITT (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC
    Measure Participants 41 44
    Number [Proportion of participants]
    .195
    0.4%
    .295
    0.5%
    4. Secondary Outcome
    Title Pharmacokinetics
    Description Mean trough serum concentration measured before final dose of epratuzumab.
    Time Frame Up to day 36

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetics (PK) were added to the protocol with amendment 5A for the twice weekly dosing schedule of Epratuzumab. Hence, PK studies were limited to evaluable patients on this Arm only.
    Arm/Group Title Twice Weekly Dosing Schedule
    Arm/Group Description Epratuzumab 360 mg/m2 x 8 doses - Part B (Amendment 5)
    Measure Participants 26
    Mean (Standard Deviation) [ug/mL]
    501
    (149)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
    Arm/Group Title Reinduction Chemoimmunotherapy With Epratuzumab Once Weekly Reinduction Chemoimmunotherapy With Epratuzumab Twice Weekly
    Arm/Group Description Four weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 8, 15, 22. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, HD methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), ITT (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC Eight 8 twice-weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 4, 8, 11, 15, 18, 22 & 25. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, HD methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), ITT (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC
    All Cause Mortality
    Reinduction Chemoimmunotherapy With Epratuzumab Once Weekly Reinduction Chemoimmunotherapy With Epratuzumab Twice Weekly
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Reinduction Chemoimmunotherapy With Epratuzumab Once Weekly Reinduction Chemoimmunotherapy With Epratuzumab Twice Weekly
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 16/54 (29.6%) 20/60 (33.3%)
    Blood and lymphatic system disorders
    Anemia 4/54 (7.4%) 4 2/60 (3.3%) 2
    Disseminated intravascular coagulation 1/54 (1.9%) 1 2/60 (3.3%) 2
    Febrile neutropenia 5/54 (9.3%) 5 11/60 (18.3%) 11
    Cardiac disorders
    Cardiac arrest 1/54 (1.9%) 1 0/60 (0%) 0
    Cardiac disorders - Other 1/54 (1.9%) 1 0/60 (0%) 0
    Conduction disorder 0/54 (0%) 0 1/60 (1.7%) 1
    Sinus bradycardia 0/54 (0%) 0 3/60 (5%) 3
    Sinus tachycardia 1/54 (1.9%) 1 2/60 (3.3%) 2
    Ventricular arrhythmia 0/54 (0%) 0 1/60 (1.7%) 1
    Gastrointestinal disorders
    Abdominal pain 2/54 (3.7%) 2 4/60 (6.7%) 4
    Colitis 0/54 (0%) 0 1/60 (1.7%) 1
    Colonic fistula 0/54 (0%) 0 1/60 (1.7%) 1
    Colonic perforation 1/54 (1.9%) 1 1/60 (1.7%) 1
    Constipation 0/54 (0%) 0 1/60 (1.7%) 1
    Diarrhea 0/54 (0%) 0 1/60 (1.7%) 1
    Enterocolitis 0/54 (0%) 0 1/60 (1.7%) 1
    Gastroparesis 0/54 (0%) 0 1/60 (1.7%) 1
    Mucositis oral 0/54 (0%) 0 1/60 (1.7%) 1
    Nausea 0/54 (0%) 0 1/60 (1.7%) 1
    Oral pain 0/54 (0%) 0 1/60 (1.7%) 1
    Pancreatitis 2/54 (3.7%) 2 2/60 (3.3%) 2
    Vomiting 0/54 (0%) 0 1/60 (1.7%) 1
    General disorders
    Chills 0/54 (0%) 0 1/60 (1.7%) 1
    Death NOS 0/54 (0%) 0 2/60 (3.3%) 2
    Edema limbs 2/54 (3.7%) 2 1/60 (1.7%) 1
    Pain 0/54 (0%) 0 1/60 (1.7%) 1
    Hepatobiliary disorders
    Hepatic failure 1/54 (1.9%) 1 2/60 (3.3%) 2
    Immune system disorders
    Anaphylaxis 1/54 (1.9%) 1 1/60 (1.7%) 1
    Infections and infestations
    Catheter related infection 1/54 (1.9%) 1 2/60 (3.3%) 2
    Enterocolitis infectious 1/54 (1.9%) 1 1/60 (1.7%) 1
    Eye infection 1/54 (1.9%) 1 0/60 (0%) 0
    Infections and infestations - Other 16/54 (29.6%) 21 20/60 (33.3%) 21
    Sepsis 0/54 (0%) 0 2/60 (3.3%) 2
    Skin infection 1/54 (1.9%) 1 0/60 (0%) 0
    Upper respiratory infection 0/54 (0%) 0 1/60 (1.7%) 1
    Injury, poisoning and procedural complications
    Vascular access complication 1/54 (1.9%) 1 1/60 (1.7%) 1
    Investigations
    Activated partial thromboplastin time prolonged 1/54 (1.9%) 1 1/60 (1.7%) 1
    Alanine aminotransferase increased 3/54 (5.6%) 3 5/60 (8.3%) 5
    Aspartate aminotransferase increased 4/54 (7.4%) 4 4/60 (6.7%) 4
    Blood bilirubin increased 3/54 (5.6%) 3 1/60 (1.7%) 1
    Creatinine increased 1/54 (1.9%) 1 0/60 (0%) 0
    Electrocardiogram QT corrected interval prolonged 0/54 (0%) 0 1/60 (1.7%) 1
    Fibrinogen decreased 4/54 (7.4%) 4 0/60 (0%) 0
    GGT increased 3/54 (5.6%) 3 0/60 (0%) 0
    INR increased 2/54 (3.7%) 2 1/60 (1.7%) 1
    Lipase increased 5/54 (9.3%) 5 4/60 (6.7%) 4
    Lymphocyte count decreased 3/54 (5.6%) 3 0/60 (0%) 0
    Neutrophil count decreased 5/54 (9.3%) 5 2/60 (3.3%) 2
    Platelet count decreased 4/54 (7.4%) 5 2/60 (3.3%) 2
    Serum amylase increased 1/54 (1.9%) 1 2/60 (3.3%) 2
    White blood cell decreased 5/54 (9.3%) 5 2/60 (3.3%) 2
    Metabolism and nutrition disorders
    Acidosis 0/54 (0%) 0 1/60 (1.7%) 1
    Alkalosis 1/54 (1.9%) 1 1/60 (1.7%) 1
    Anorexia 1/54 (1.9%) 1 2/60 (3.3%) 2
    Dehydration 0/54 (0%) 0 1/60 (1.7%) 1
    Glucose intolerance 1/54 (1.9%) 1 0/60 (0%) 0
    Hyperglycemia 4/54 (7.4%) 4 2/60 (3.3%) 2
    Hyperkalemia 2/54 (3.7%) 2 0/60 (0%) 0
    Hypertriglyceridemia 0/54 (0%) 0 1/60 (1.7%) 1
    Hypoalbuminemia 2/54 (3.7%) 2 3/60 (5%) 3
    Hypocalcemia 4/54 (7.4%) 4 0/60 (0%) 0
    Hypoglycemia 0/54 (0%) 0 1/60 (1.7%) 1
    Hypokalemia 3/54 (5.6%) 3 4/60 (6.7%) 4
    Hyponatremia 4/54 (7.4%) 4 1/60 (1.7%) 1
    Hypophosphatemia 2/54 (3.7%) 2 0/60 (0%) 0
    Musculoskeletal and connective tissue disorders
    Abdominal soft tissue necrosis 0/54 (0%) 0 1/60 (1.7%) 1
    Arthralgia 1/54 (1.9%) 1 0/60 (0%) 0
    Pain in extremity 1/54 (1.9%) 1 1/60 (1.7%) 1
    Nervous system disorders
    Cognitive disturbance 0/54 (0%) 0 1/60 (1.7%) 1
    Dizziness 0/54 (0%) 0 1/60 (1.7%) 1
    Dysphasia 0/54 (0%) 0 1/60 (1.7%) 1
    Encephalopathy 0/54 (0%) 0 2/60 (3.3%) 2
    Headache 0/54 (0%) 0 1/60 (1.7%) 1
    Intracranial hemorrhage 0/54 (0%) 0 1/60 (1.7%) 1
    Nervous system disorders - Other 0/54 (0%) 0 2/60 (3.3%) 2
    Peripheral motor neuropathy 1/54 (1.9%) 1 0/60 (0%) 0
    Seizure 0/54 (0%) 0 1/60 (1.7%) 1
    Anxiety 1/54 (1.9%) 1 0/60 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 2/54 (3.7%) 2 1/60 (1.7%) 1
    Hematuria 1/54 (1.9%) 1 0/60 (0%) 0
    Proteinuria 1/54 (1.9%) 1 0/60 (0%) 0
    Renal and urinary disorders - Other 1/54 (1.9%) 1 1/60 (1.7%) 1
    Urinary frequency 1/54 (1.9%) 1 0/60 (0%) 0
    Urinary tract pain 0/54 (0%) 0 1/60 (1.7%) 1
    Respiratory, thoracic and mediastinal disorders
    Apnea 0/54 (0%) 0 2/60 (3.3%) 2
    Epistaxis 0/54 (0%) 0 1/60 (1.7%) 1
    Hypoxia 4/54 (7.4%) 4 1/60 (1.7%) 1
    Pleural effusion 1/54 (1.9%) 1 0/60 (0%) 0
    Pneumonitis 2/54 (3.7%) 2 0/60 (0%) 0
    Skin and subcutaneous tissue disorders
    Purpura 0/54 (0%) 0 1/60 (1.7%) 1
    Skin and subcutaneous tissue disorders - Other 0/54 (0%) 0 1/60 (1.7%) 1
    Skin ulceration 0/54 (0%) 0 1/60 (1.7%) 1
    Vascular disorders
    Capillary leak syndrome 1/54 (1.9%) 1 0/60 (0%) 0
    Hypertension 2/54 (3.7%) 2 2/60 (3.3%) 2
    Hypotension 4/54 (7.4%) 4 3/60 (5%) 3
    Vascular disorders - Other 1/54 (1.9%) 1 0/60 (0%) 0
    Other (Not Including Serious) Adverse Events
    Reinduction Chemoimmunotherapy With Epratuzumab Once Weekly Reinduction Chemoimmunotherapy With Epratuzumab Twice Weekly
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 44/54 (81.5%) 41/60 (68.3%)
    Blood and lymphatic system disorders
    Anemia 36/54 (66.7%) 45 41/60 (68.3%) 49
    Febrile neutropenia 18/54 (33.3%) 18 22/60 (36.7%) 23
    Cardiac disorders
    Sinus bradycardia 1/54 (1.9%) 1 0/60 (0%) 0
    Eye disorders
    Eye disorders - Other 1/54 (1.9%) 1 1/60 (1.7%) 1
    Eye pain 0/54 (0%) 0 1/60 (1.7%) 1
    Photophobia 1/54 (1.9%) 1 1/60 (1.7%) 1
    Gastrointestinal disorders
    Abdominal distension 1/54 (1.9%) 1 0/60 (0%) 0
    Abdominal pain 3/54 (5.6%) 3 0/60 (0%) 0
    Diarrhea 2/54 (3.7%) 2 3/60 (5%) 3
    Ileus 1/54 (1.9%) 1 0/60 (0%) 0
    Mucositis oral 4/54 (7.4%) 4 5/60 (8.3%) 5
    Nausea 3/54 (5.6%) 3 3/60 (5%) 3
    Oral pain 2/54 (3.7%) 2 1/60 (1.7%) 1
    Pancreatitis 5/54 (9.3%) 5 2/60 (3.3%) 2
    Rectal hemorrhage 1/54 (1.9%) 1 0/60 (0%) 0
    Typhlitis 2/54 (3.7%) 2 0/60 (0%) 0
    Vomiting 2/54 (3.7%) 2 2/60 (3.3%) 2
    General disorders
    Fatigue 1/54 (1.9%) 1 1/60 (1.7%) 1
    Fever 0/54 (0%) 0 2/60 (3.3%) 2
    Irritability 1/54 (1.9%) 1 0/60 (0%) 0
    Pain 1/54 (1.9%) 1 4/60 (6.7%) 4
    Immune system disorders
    Anaphylaxis 2/54 (3.7%) 2 0/60 (0%) 0
    Infections and infestations
    Catheter related infection 0/54 (0%) 0 1/60 (1.7%) 1
    Enterocolitis infectious 3/54 (5.6%) 3 3/60 (5%) 3
    Infections and infestations - Other 28/54 (51.9%) 29 19/60 (31.7%) 20
    Mucosal infection 0/54 (0%) 0 1/60 (1.7%) 1
    Penile infection 1/54 (1.9%) 1 0/60 (0%) 0
    Sepsis 0/54 (0%) 0 1/60 (1.7%) 1
    Skin infection 0/54 (0%) 0 2/60 (3.3%) 2
    Small intestine infection 1/54 (1.9%) 1 0/60 (0%) 0
    Investigations
    Activated partial thromboplastin time prolonged 1/54 (1.9%) 1 2/60 (3.3%) 2
    Alanine aminotransferase increased 8/54 (14.8%) 8 15/60 (25%) 16
    Alkaline phosphatase increased 0/54 (0%) 0 1/60 (1.7%) 1
    Aspartate aminotransferase increased 9/54 (16.7%) 9 11/60 (18.3%) 12
    Blood bilirubin increased 1/54 (1.9%) 1 2/60 (3.3%) 2
    Fibrinogen decreased 2/54 (3.7%) 2 5/60 (8.3%) 5
    GGT increased 3/54 (5.6%) 3 1/60 (1.7%) 1
    Lipase increased 6/54 (11.1%) 6 4/60 (6.7%) 4
    Lymphocyte count decreased 10/54 (18.5%) 15 22/60 (36.7%) 29
    Neutrophil count decreased 38/54 (70.4%) 43 40/60 (66.7%) 42
    Platelet count decreased 39/54 (72.2%) 54 38/60 (63.3%) 46
    Serum amylase increased 3/54 (5.6%) 3 1/60 (1.7%) 1
    Weight gain 1/54 (1.9%) 1 0/60 (0%) 0
    Weight loss 1/54 (1.9%) 1 1/60 (1.7%) 1
    White blood cell decreased 34/54 (63%) 44 40/60 (66.7%) 44
    Metabolism and nutrition disorders
    Acidosis 3/54 (5.6%) 3 2/60 (3.3%) 3
    Alkalosis 0/54 (0%) 0 2/60 (3.3%) 2
    Anorexia 5/54 (9.3%) 5 6/60 (10%) 6
    Dehydration 3/54 (5.6%) 3 1/60 (1.7%) 1
    Glucose intolerance 0/54 (0%) 0 1/60 (1.7%) 1
    Hypercalcemia 1/54 (1.9%) 1 0/60 (0%) 0
    Hyperglycemia 18/54 (33.3%) 20 15/60 (25%) 15
    Hyperkalemia 4/54 (7.4%) 4 0/60 (0%) 0
    Hypernatremia 4/54 (7.4%) 4 0/60 (0%) 0
    Hypertriglyceridemia 2/54 (3.7%) 2 1/60 (1.7%) 1
    Hyperuricemia 2/54 (3.7%) 3 0/60 (0%) 0
    Hypoalbuminemia 10/54 (18.5%) 10 7/60 (11.7%) 7
    Hypocalcemia 9/54 (16.7%) 10 8/60 (13.3%) 8
    Hypoglycemia 0/54 (0%) 0 1/60 (1.7%) 1
    Hypokalemia 16/54 (29.6%) 16 16/60 (26.7%) 19
    Hypomagnesemia 2/54 (3.7%) 2 0/60 (0%) 0
    Hyponatremia 11/54 (20.4%) 11 9/60 (15%) 9
    Hypophosphatemia 3/54 (5.6%) 3 5/60 (8.3%) 5
    Tumor lysis syndrome 0/54 (0%) 0 1/60 (1.7%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/54 (1.9%) 1 0/60 (0%) 0
    Back pain 3/54 (5.6%) 3 4/60 (6.7%) 4
    Bone pain 1/54 (1.9%) 1 0/60 (0%) 0
    Buttock pain 1/54 (1.9%) 1 1/60 (1.7%) 1
    Generalized muscle weakness 1/54 (1.9%) 1 0/60 (0%) 0
    Neck pain 1/54 (1.9%) 1 0/60 (0%) 0
    Pain in extremity 4/54 (7.4%) 4 2/60 (3.3%) 2
    Nervous system disorders
    Arachnoiditis 1/54 (1.9%) 1 0/60 (0%) 0
    Headache 3/54 (5.6%) 3 2/60 (3.3%) 2
    Syncope 2/54 (3.7%) 2 0/60 (0%) 0
    Renal and urinary disorders
    Proteinuria 1/54 (1.9%) 1 0/60 (0%) 0
    Renal and urinary disorders - Other 0/54 (0%) 0 1/60 (1.7%) 1
    Respiratory, thoracic and mediastinal disorders
    Adult respiratory distress syndrome 1/54 (1.9%) 1 0/60 (0%) 0
    Epistaxis 1/54 (1.9%) 1 3/60 (5%) 3
    Hypoxia 2/54 (3.7%) 2 3/60 (5%) 3
    Pharyngolaryngeal pain 2/54 (3.7%) 2 0/60 (0%) 0
    Pleural effusion 1/54 (1.9%) 1 0/60 (0%) 0
    Pneumonitis 2/54 (3.7%) 2 0/60 (0%) 0
    Skin and subcutaneous tissue disorders
    Rash maculo-papular 0/54 (0%) 0 1/60 (1.7%) 1
    Skin and subcutaneous tissue disorders - Other 0/54 (0%) 0 1/60 (1.7%) 1
    Vascular disorders
    Hypertension 2/54 (3.7%) 2 1/60 (1.7%) 1
    Hypotension 5/54 (9.3%) 5 2/60 (3.3%) 2
    Vascular disorders - Other 0/54 (0%) 0 1/60 (1.7%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    Must obtain prior 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:
    NCT00098839
    Other Study ID Numbers:
    • ADVL04P2
    • NCI-2011-01624
    • COG-ADVL04P2
    • CDR0000396777
    • U10CA098543
    First Posted:
    Dec 9, 2004
    Last Update Posted:
    Dec 12, 2017
    Last Verified:
    Nov 1, 2017