A Pilot Study of Decitabine and Vorinostat With Chemotherapy for Relapsed ALL

Sponsor
Therapeutic Advances in Childhood Leukemia Consortium (Other)
Overall Status
Terminated
CT.gov ID
NCT01483690
Collaborator
(none)
23
Enrollment
28
Locations
2
Arms
44
Duration (Months)
0.8
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a pilot study using decitabine and vorinostat before and during chemotherapy with vincristine, dexamethasone, mitoxantrone, and peg-asparaginase in pediatric patients with acute lymphoblastic leukemia (ALL).

Detailed Description

Decitabine is a demethylating agent and vorinostat is a HDAC inhibitor. The use of demethylating agents and HDAC inhibitors in combination have been previously shown to have synergistic effects in altering neoplastic pathways of cancer cells and be well tolerated in human clinical studies. With the ability of decitabine and vorinostat to alter the abnormal cellular pathways of leukemic blasts and essentially turn off anti-apoptotic proteins, the leukemia cells have become primed for cytotoxic cell kill via chemotherapeutic agents. This study will ask the question as to whether or not the combination of decitabine and vorinostat followed by chemotherapy is feasible and whether it can positively impact outcome in patients with relapsed or refractory acute lymphoblastic leukemia.

Study Design

Study Type:
Interventional
Actual Enrollment :
23 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Pilot Study of Decitabine and Vorinostat With Chemotherapy for Relapsed ALL
Study Start Date :
Dec 1, 2011
Actual Primary Completion Date :
Jul 31, 2015
Actual Study Completion Date :
Jul 31, 2015

Arms and Interventions

ArmIntervention/Treatment
Experimental: Initial Dose Level

Decitabine 15 mg/m2/day given IV over 1 hour on days 1 through 7 and days 15 through 21. Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 3 through 10 and days 17 through 24

Drug: Decitabine
10 mg/m2/day given IV over 1 hour on days 1 through 5 and days 15 through 19.
Other Names:
  • Dacogen
  • Drug: Vorinostat
    180 mg/m2/day (Max dose=400mg daily) given orally on days 2 through 7 and days 16 through 21.
    Other Names:
  • Zolinza
  • suberoylanilide hydroxamic acid (SAHA)
  • Drug: Vincristine
    1.5 mg/m2/day (Max dose 2 mg) given IV push on days 10, 17, 24 and 31.
    Other Names:
  • Oncovin
  • Vincasar PFS
  • Vincrex
  • vincristine sulfate
  • VCR
  • Drug: Dexamethasone
    20 mg/m2/day divided BID given orally on days 8 through 12 and 22 through 26.
    Other Names:
  • Decadron
  • Dexamethasone Intensol
  • dexamethasone acetate
  • dexamethasone sodium phosphate
  • Drug: Mitoxantrone
    10 mg/m2/day given on days 8 and 9 as a short IV infusion over 5-15 minutes; do not infuse over less than 3 minutes
    Other Names:
  • Novantrone
  • DHAD
  • DHAQ
  • Drug: Pegaspargase
    2500 international units/m2/day IM or IV on days 10 and 24.
    Other Names:
  • Oncospar
  • PEG-L-asparaginase
  • Drug: Methotrexate
    Given intrathecally to all patients the dose defined by age below. 8 mg for patients age 1-1.99 10 mg for patients age 2-2.99 12 mg for patients 3-8.99 years of age 15 mg for patients >9 years of age CNS 1 or 2 patients get doses on day 8, 22 and 35 and CNS 3 patients should get doses on day 8, 15, 22, 29 and 35
    Other Names:
  • Folex
  • Mexate
  • MTX
  • Methotrex
  • Experimental: Modified Dose Level

    Decitabine 10 mg/m2/day given IV over 1 hour on days 1 through 5 and days 15 through 19. Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 2 through 7 and days 16 through 21

    Drug: Decitabine
    10 mg/m2/day given IV over 1 hour on days 1 through 5 and days 15 through 19.
    Other Names:
  • Dacogen
  • Drug: Vorinostat
    180 mg/m2/day (Max dose=400mg daily) given orally on days 2 through 7 and days 16 through 21.
    Other Names:
  • Zolinza
  • suberoylanilide hydroxamic acid (SAHA)
  • Drug: Vincristine
    1.5 mg/m2/day (Max dose 2 mg) given IV push on days 10, 17, 24 and 31.
    Other Names:
  • Oncovin
  • Vincasar PFS
  • Vincrex
  • vincristine sulfate
  • VCR
  • Drug: Dexamethasone
    20 mg/m2/day divided BID given orally on days 8 through 12 and 22 through 26.
    Other Names:
  • Decadron
  • Dexamethasone Intensol
  • dexamethasone acetate
  • dexamethasone sodium phosphate
  • Drug: Mitoxantrone
    10 mg/m2/day given on days 8 and 9 as a short IV infusion over 5-15 minutes; do not infuse over less than 3 minutes
    Other Names:
  • Novantrone
  • DHAD
  • DHAQ
  • Drug: Pegaspargase
    2500 international units/m2/day IM or IV on days 10 and 24.
    Other Names:
  • Oncospar
  • PEG-L-asparaginase
  • Drug: Methotrexate
    Given intrathecally to all patients the dose defined by age below. 8 mg for patients age 1-1.99 10 mg for patients age 2-2.99 12 mg for patients 3-8.99 years of age 15 mg for patients >9 years of age CNS 1 or 2 patients get doses on day 8, 22 and 35 and CNS 3 patients should get doses on day 8, 15, 22, 29 and 35
    Other Names:
  • Folex
  • Mexate
  • MTX
  • Methotrex
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participants Who Experienced a Dose Limiting Toxicity (DLT). [6 weeks]

      To evaluate the side effects of giving decitabine and vorinostat before and during chemotherapy using the standard drugs vincristine, dexamethasone, PEG-asparaginase and mitoxantrone.

    Secondary Outcome Measures

    1. Disease Response Rate After Treatment. [6 weeks]

      Bone marrow evaluation was performed on Day 35 of study to evaluate treatment response. CR defined as attaining M1 marrow (<5% blasts) with no evidence of circulating blasts or extramedullary disease in addition to recovery of peripheral blood counts (ANC >750/uL and platelet count >75,000/uL). CRp was defined as attaining an M1 marrow with no evidence of circulating blasts or extramedullary disease in addition to recovery of ANC but insufficient recovery of platelets. CRi was attaining M1 marrow with no evidence of circulating blasts or extramedullary disease but insufficient recovery of ANC with or without sufficient recovery of platelets. PR was defined as no evidence of circulating blasts and achievement of M2 marrow (5-25% blasts) without new sites of disease and with recovery of ANC. SD is for patients who did not meet the criteria for PR, CR, CRp, or CRi. PD is an increase of at least 25% in the absolute number of leukemia cells or development of new sites.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    1 Year to 21 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients must be ≥1 and ≤ 21 years of age when originally diagnosed with ALL.

    Diagnosis

    • Patients must have a diagnosis of acute lymphoblastic leukemia (ALL) with ≥ 25% blasts in the bone marrow (M3), with or without extramedullary disease.

    • Patients may have CNS 1, 2 or 3 disease.

    • Karnofsky > 50% for patients > 16 years of age and Lansky > 50% for patients ≤ 16 years of age.

    • Prior Therapy

    • Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

    • Patients must have had 2 or more prior therapeutic attempts defined as:

    • Relapse after going into remission from re-induction for the first or subsequent relapse (ie: 2nd , 3rd, 4th…relapse), OR

    • Refractory disease after first or greater relapse and a re-induction attempt, OR

    • Failing to go into remission from original diagnosis after 2 previous induction attempts.

    • Hematopoietic Stem Cell Transplant: Patients who have experienced their relapse after a HSCT are eligible, provided they have no evidence of Graft-versus-Host Disease (GVHD) and are at least 60 days post-transplant at the time of enrollment.

    • Prior anthracycline exposure: Patients must have less than 400 mg/m2 lifetime exposure of anthracycline chemotherapy. (See Appendix II for calculation worksheet)

    • Hematopoietic grow factors: It must have been at least 7 days since the completion of therapy with GCSF or other growth factors at the time of enrollment. It must have been at least 14 days since the completion of therapy with pegfilgrastim (Neulasta®).

    • Biologic (anti-neoplastic) therapy: It must be at least 7 days after last does of biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair

    • Monoclonal antibodies: At least 3 half-lives of the antibody must have elapsed after the last dose of monoclonal antibody. (ie. Rituximab=66 days, Epratuzumab=69 days)

    • Immunotherapy: At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines.

    Renal and Hepatic Function

    • Patient's serum creatinine must be ≤ 1.5 x institutional upper limit of normal (ULN) according to age. If the serum creatinine is greater than 1.5 times normal, the patient must have a calculated creatinine clearance or radioisotope GRF ≥ 70mL/min/1.73m2.

    • Patient's ALT and AST must be < 5 x institutional upper limit of norm ULN. The hepatic requirements are waived for patients with known or suspected liver involvement who would otherwise be eligible after consultation with the Study Chair or Vice Chair.

    • Patient's total bilirubin must be ≤ 1.5 x ULN. The hepatic requirements are waived for patients with known or suspected liver involvement who would otherwise be eligible.

    Cardiac Function:
    • Patient must have a shortening fraction ≥ 27% by Echo or an ejection fraction ≥ 50% by MUGA.

    Reproductive Function

    • Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed prior to enrollment.

    • Female patients with infants must agree not to breastfeed their infants while on this study.

    • Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study.

    Exclusion Criteria:
    • Patients will be excluded if they are receiving Valproic Acid (VPA) therapy.

    • Patients will be excluded if they have a known allergy to any of the drugs used in the study.

    • Patients will be excluded if they have a systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment.

    • Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period.

    • Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results.

    • Patients will be excluded if they have had any positive fungal culture in the last 30 days prior to enrollment.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Childrens Hospital Los AngelesLos AngelesCaliforniaUnited States90027
    2CHOCOrangeCaliforniaUnited States
    3UCSF School of MedicineSan FranciscoCaliforniaUnited States94143-0106
    4The Children's Hospital, University of ColoradoAuroraColoradoUnited States80045
    5Children's National Medical CenterWashingtonDistrict of ColumbiaUnited States
    6University of Miami Cancer CenterMiamiFloridaUnited States33136
    7Children's Healthcare of Atlanta, Emory UniversityAtlantaGeorgiaUnited States
    8Lurie Children's HospitalChicagoIllinoisUnited States
    9Johns Hopkins UniversityBaltimoreMarylandUnited States
    10Dana FarberBostonMassachusettsUnited States
    11C.S. Mott Children's HospitalAnn ArborMichiganUnited States48109-0914
    12Childrens Hospital & Clinics of MinnesotaMinneapolisMinnesotaUnited States55404-4597
    13University of Minnesota Children's HospitalMinneapolisMinnesotaUnited States
    14Children's Mercy Hospitals and ClinicsKansas CityMissouriUnited States64108
    15New York University Medical CenterNew YorkNew YorkUnited States10016
    16Children's Hospital New York-PresbyterianNew YorkNew YorkUnited States10032
    17Levine Children's Hospital at Carolinas Medical CenterCharlotteNorth CarolinaUnited States28203
    18Nationwide Childrens HospitalColumbusOhioUnited States
    19Oregon Health and Science UniversityPortlandOregonUnited States
    20Children's Hospital of PhiladelphiaPhiladelphiaPennsylvaniaUnited States19104
    21St. JudeMemphisTennesseeUnited States38105-3678
    22Vanderbilt Children's HospitalNashvilleTennesseeUnited States
    23University of Texas at SouthwesternDallasTexasUnited States
    24Cook Children's Medical CenterFort WorthTexasUnited States76104
    25Seattle Children's HospitalSeattleWashingtonUnited States98105
    26Children's Hospital at WestmeadWestmeadNew South WalesAustralia
    27Royal Children's HospitalBrisbaneQueenslandAustralia
    28Sydney Children's HospitalSydneyAustralia

    Sponsors and Collaborators

    • Therapeutic Advances in Childhood Leukemia Consortium

    Investigators

    • Study Chair: Michael Burke, MD, Medical College of Wisconsin

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Therapeutic Advances in Childhood Leukemia Consortium
    ClinicalTrials.gov Identifier:
    NCT01483690
    Other Study ID Numbers:
    • T2009-003
    First Posted:
    Dec 1, 2011
    Last Update Posted:
    Oct 27, 2020
    Last Verified:
    Oct 1, 2020

    Study Results

    Participant Flow

    Recruitment DetailsThis is a pilot study where 16 patients are anticipated to be enrolled. Anticipated enrollment will take 2.5 years.
    Pre-assignment Detail
    Arm/Group TitleInitial Dose LevelModified Dose Level
    Arm/Group DescriptionDecitabine 15 mg/m2/day given IV over 1 hour on days 1 through 7 and days 15 through 21. Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 3 through 10 and days 17 through 24Decitabine 10 mg/m2/day given IV over 1 hour on days 1 through 5 and days 15 through 19. Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 2 through 7 and days 16 through 21
    Period Title: Overall Study
    STARTED518
    COMPLETED313
    NOT COMPLETED25

    Baseline Characteristics

    Arm/Group TitleInitial Dose LevelModified Dose LevelTotal
    Arm/Group DescriptionDecitabine 15 mg/m2/day given IV over 1 hour on days 1 through 7 and days 15 through 21. Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 3 through 10 and days 17 through 24Decitabine 10 mg/m2/day given IV over 1 hour on days 1 through 5 and days 15 through 19. Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 2 through 7 and days 16 through 21Total of all reporting groups
    Overall Participants51823
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    12.5
    12.0
    12.0
    Sex: Female, Male (Count of Participants)
    Female
    2
    40%
    4
    22.2%
    6
    26.1%
    Male
    3
    60%
    14
    77.8%
    17
    73.9%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    3
    60%
    9
    50%
    12
    52.2%
    Not Hispanic or Latino
    2
    40%
    9
    50%
    11
    47.8%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    1
    5.6%
    1
    4.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    2
    11.1%
    2
    8.7%
    White
    5
    100%
    10
    55.6%
    15
    65.2%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    5
    27.8%
    5
    21.7%
    CNS Status (Count of Participants)
    CNS 1
    4
    80%
    14
    77.8%
    18
    78.3%
    CNS 2
    1
    20%
    2
    11.1%
    3
    13%
    CNS 3
    0
    0%
    2
    11.1%
    2
    8.7%
    Prior hematopoietic cell transplantation (HCT) (Count of Participants)
    Yes had prior HCT
    3
    60%
    8
    44.4%
    11
    47.8%
    No did not have prior HCT
    2
    40%
    10
    55.6%
    12
    52.2%
    Relapse # at enrollment (Count of Participants)
    2nd Relapse
    2
    40%
    13
    72.2%
    15
    65.2%
    3rd Relapse
    1
    20%
    1
    5.6%
    2
    8.7%
    Refractory
    2
    40%
    4
    22.2%
    6
    26.1%

    Outcome Measures

    1. Primary Outcome
    TitleNumber of Participants Who Experienced a Dose Limiting Toxicity (DLT).
    DescriptionTo evaluate the side effects of giving decitabine and vorinostat before and during chemotherapy using the standard drugs vincristine, dexamethasone, PEG-asparaginase and mitoxantrone.
    Time Frame6 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants who entered the study.
    Arm/Group TitleInitial Dose LevelModified Dose Level
    Arm/Group DescriptionDecitabine 15 mg/m2/day given IV over 1 hour on days 1 through 7 and days 15 through 21. Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 3 through 10 and days 17 through 24Decitabine 10 mg/m2/day given IV over 1 hour on days 1 through 5 and days 15 through 19. Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 2 through 7 and days 16 through 21
    Measure Participants518
    # of patients with DLT
    2
    40%
    1
    5.6%
    # of patients without DLT
    2
    40%
    12
    66.7%
    # of patients not evaluable
    1
    20%
    5
    27.8%
    2. Secondary Outcome
    TitleDisease Response Rate After Treatment.
    DescriptionBone marrow evaluation was performed on Day 35 of study to evaluate treatment response. CR defined as attaining M1 marrow (<5% blasts) with no evidence of circulating blasts or extramedullary disease in addition to recovery of peripheral blood counts (ANC >750/uL and platelet count >75,000/uL). CRp was defined as attaining an M1 marrow with no evidence of circulating blasts or extramedullary disease in addition to recovery of ANC but insufficient recovery of platelets. CRi was attaining M1 marrow with no evidence of circulating blasts or extramedullary disease but insufficient recovery of ANC with or without sufficient recovery of platelets. PR was defined as no evidence of circulating blasts and achievement of M2 marrow (5-25% blasts) without new sites of disease and with recovery of ANC. SD is for patients who did not meet the criteria for PR, CR, CRp, or CRi. PD is an increase of at least 25% in the absolute number of leukemia cells or development of new sites.
    Time Frame6 weeks

    Outcome Measure Data

    Analysis Population Description
    Patients who entered the study.
    Arm/Group TitleInitial Dose LevelModified Dose Level
    Arm/Group DescriptionDecitabine 15 mg/m2/day given IV over 1 hour on days 1 through 7 and days 15 through 21. Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 3 through 10 and days 17 through 24Decitabine 10 mg/m2/day given IV over 1 hour on days 1 through 5 and days 15 through 19. Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 2 through 7 and days 16 through 21
    Measure Participants518
    complete response (CR)
    0
    0%
    1
    5.6%
    complete response without platelet recovery (CRp)
    1
    20%
    3
    16.7%
    complete remission with incomplete recovery (CRi)
    1
    20%
    3
    16.7%
    stable disease (SD)
    1
    20%
    4
    22.2%
    patient not evaluable for response
    2
    40%
    7
    38.9%

    Adverse Events

    Time FrameAdverse events and suspected adverse reactions will be collected and reported on the electronic case report forms beginning with the first dose of decitabine and vorinostat until 30 days following last dose of decitabine and vorinostat.
    Adverse Event Reporting Description The definition of adverse event and/or serious adverse event used to collect adverse event information is the same from clinicaltrials.gov definitions.
    Arm/Group TitleInitial Dose LevelModified Dose Level
    Arm/Group DescriptionDecitabine 15 mg/m2/day given IV over 1 hour on days 1 through 7 and days 15 through 21. Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 3 through 10 and days 17 through 24Decitabine 10 mg/m2/day given IV over 1 hour on days 1 through 5 and days 15 through 19. Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 2 through 7 and days 16 through 21
    All Cause Mortality
    Initial Dose LevelModified Dose Level
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total5/5 (100%) 13/18 (72.2%)
    Serious Adverse Events
    Initial Dose LevelModified Dose Level
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total5/5 (100%) 18/18 (100%)
    Blood and lymphatic system disorders
    neutrophil count decrease2/5 (40%) 5/18 (27.8%)
    platelet count decreased2/5 (40%) 7/18 (38.9%)
    white blood cell decreased2/5 (40%) 6/18 (33.3%)
    Bone marrow hypocellular1/5 (20%) 0/18 (0%)
    Capillary leak syndrome1/5 (20%) 0/18 (0%)
    Cardiac disorders
    Hypotension0/5 (0%) 2/18 (11.1%)
    Left ventricular systolic dysfunction1/5 (20%) 1/18 (5.6%)
    sinus bradycardia0/5 (0%) 2/18 (11.1%)
    Right ventricular dysfunction1/5 (20%) 0/18 (0%)
    Endocrine disorders
    Acute kidney injury0/5 (0%) 2/18 (11.1%)
    Gastrointestinal disorders
    Gastrointestinal disorder - Other1/5 (20%) 0/18 (0%)
    General disorders
    Somnolence1/5 (20%) 0/18 (0%)
    Infections and infestations
    Ano-rectal infection0/5 (0%) 1/18 (5.6%)
    Lung infection0/5 (0%) 1/18 (5.6%)
    sepsis2/5 (40%) 4/18 (22.2%)
    soft tissue infection0/5 (0%) 1/18 (5.6%)
    Metabolism and nutrition disorders
    Anemia1/5 (20%) 11/18 (61.1%)
    Acidosis0/5 (0%) 2/18 (11.1%)
    Alanine aminotransferase increase0/5 (0%) 2/18 (11.1%)
    Alkaline phosphatase increased0/5 (0%) 3/18 (16.7%)
    Blood bilirubin increased1/5 (20%) 2/18 (11.1%)
    GGT increased0/5 (0%) 1/18 (5.6%)
    Hypercalcemia0/5 (0%) 1/18 (5.6%)
    Hyperglycemia1/5 (20%) 1/18 (5.6%)
    Hyperkalemia0/5 (0%) 1/18 (5.6%)
    Hypermagnesemia0/5 (0%) 1/18 (5.6%)
    Hypernatermia1/5 (20%) 1/18 (5.6%)
    Hypertriglyceridemia1/5 (20%) 1/18 (5.6%)
    Hyperuricemia0/5 (0%) 1/18 (5.6%)
    Hypocalcemia0/5 (0%) 1/18 (5.6%)
    Hypokalemia2/5 (40%) 9/18 (50%)
    Hypophosphatemia0/5 (0%) 2/18 (11.1%)
    Lipase increased1/5 (20%) 2/18 (11.1%)
    Lymphocyte count decreased2/5 (40%) 2/18 (11.1%)
    Lymphocyte count increased0/5 (0%) 1/18 (5.6%)
    serum amylase increased0/5 (0%) 1/18 (5.6%)
    Musculoskeletal and connective tissue disorders
    Agitation0/5 (0%) 1/18 (5.6%)
    Nervous system disorders
    Encephalopathy0/5 (0%) 1/18 (5.6%)
    nervous system disorder - other0/5 (0%) 1/18 (5.6%)
    Altered mental status0/5 (0%) 1/18 (5.6%)
    Reversible posterior leukoencephalopathy syndrome0/5 (0%) 1/18 (5.6%)
    Seizure1/5 (20%) 0/18 (0%)
    Respiratory, thoracic and mediastinal disorders
    Adult respiratory distress syndrome1/5 (20%) 1/18 (5.6%)
    Hypoxia0/5 (0%) 2/18 (11.1%)
    Pleural effusion0/5 (0%) 1/18 (5.6%)
    Pulmonary edema0/5 (0%) 2/18 (11.1%)
    respiratory failure1/5 (20%) 2/18 (11.1%)
    Other (Not Including Serious) Adverse Events
    Initial Dose LevelModified Dose Level
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total5/5 (100%) 18/18 (100%)
    Blood and lymphatic system disorders
    Anemia1/5 (20%) 15/18 (83.3%)
    Blood bilirubin increased1/5 (20%) 5/18 (27.8%)
    Tumor lysis syndrome1/5 (20%) 1/18 (5.6%)
    White blood cell decreased0/5 (0%) 1/18 (5.6%)
    Cardiac disorders
    Hypertension2/5 (40%) 3/18 (16.7%)
    Hypotension1/5 (20%) 2/18 (11.1%)
    Left ventricular systolic dysfunction0/5 (0%) 1/18 (5.6%)
    Gastrointestinal disorders
    Abdominal pain3/5 (60%) 0/18 (0%)
    Ascites0/5 (0%) 1/18 (5.6%)
    Colitis1/5 (20%) 0/18 (0%)
    Diarrhea1/5 (20%) 2/18 (11.1%)
    Gastric hemorrhage0/5 (0%) 2/18 (11.1%)
    Hepatobiliary disorders - Other1/5 (20%) 0/18 (0%)
    Ileus0/5 (0%) 1/18 (5.6%)
    Lower gastrointestinal hemorrhage1/5 (20%) 1/18 (5.6%)
    Pancreatitis1/5 (20%) 3/18 (16.7%)
    Rectal hemorrhage0/5 (0%) 1/18 (5.6%)
    General disorders
    Anorexia2/5 (40%) 4/18 (22.2%)
    Dehydration1/5 (20%) 1/18 (5.6%)
    Delirium1/5 (20%) 1/18 (5.6%)
    Depressed level of consciousness0/5 (0%) 1/18 (5.6%)
    Dizziness0/5 (0%) 1/18 (5.6%)
    Dyspnea0/5 (0%) 1/18 (5.6%)
    Epistaxis0/5 (0%) 1/18 (5.6%)
    Fever1/5 (20%) 0/18 (0%)
    Generalized muscle weakness1/5 (20%) 2/18 (11.1%)
    Hypoxia1/5 (20%) 3/18 (16.7%)
    Lethargy1/5 (20%) 0/18 (0%)
    Malaise0/5 (0%) 1/18 (5.6%)
    Muscle weakness0/5 (0%) 1/18 (5.6%)
    Nausea1/5 (20%) 2/18 (11.1%)
    Pain in extremity0/5 (0%) 2/18 (11.1%)
    Weight loss0/5 (0%) 2/18 (11.1%)
    Infections and infestations
    Catheter related infection1/5 (20%) 3/18 (16.7%)
    Enterocolitis infectious0/5 (0%) 2/18 (11.1%)
    Febrile neutropenia2/5 (40%) 15/18 (83.3%)
    Infective myositis1/5 (20%) 0/18 (0%)
    Lip infection0/5 (0%) 1/18 (5.6%)
    Lung infection1/5 (20%) 4/18 (22.2%)
    Lymph gland infection0/5 (0%) 1/18 (5.6%)
    Mucosal infection1/5 (20%) 2/18 (11.1%)
    Scrotal infection0/5 (0%) 1/18 (5.6%)
    Skin infection0/5 (0%) 2/18 (11.1%)
    Soft tissue infection0/5 (0%) 3/18 (16.7%)
    Typhlitis0/5 (0%) 2/18 (11.1%)
    Coagulase negative staphylococus1/5 (20%) 0/18 (0%)
    Enterococcus Faecalis2/5 (40%) 0/18 (0%)
    Candida Kruseli3/5 (60%) 0/18 (0%)
    Klebsiella pneumonae0/5 (0%) 1/18 (5.6%)
    Candida parapsilosis0/5 (0%) 1/18 (5.6%)
    Pseudomonas aeruginosa0/5 (0%) 1/18 (5.6%)
    Necrotizing fascitis0/5 (0%) 1/18 (5.6%)
    Bipolaris spicifera0/5 (0%) 1/18 (5.6%)
    Investigations
    Investigations - Other1/5 (20%) 0/18 (0%)
    Metabolism and nutrition disorders
    Acidosis0/5 (0%) 1/18 (5.6%)
    Alanine aminotransferase increased1/5 (20%) 3/18 (16.7%)
    Alkaline phosphatase increased0/5 (0%) 1/18 (5.6%)
    Aspartate aminotransferase increased1/5 (20%) 4/18 (22.2%)
    Cholesterol high0/5 (0%) 1/18 (5.6%)
    Creatinine increased0/5 (0%) 2/18 (11.1%)
    Gamma-glutamyl transferase increased1/5 (20%) 0/18 (0%)
    Hyperglycemia2/5 (40%) 3/18 (16.7%)
    Hypercalcemia0/5 (0%) 1/18 (5.6%)
    Hyperkalemia0/5 (0%) 1/18 (5.6%)
    Hypermagnesemia1/5 (20%) 0/18 (0%)
    Hypertriglyceridemia1/5 (20%) 0/18 (0%)
    Hypoalbuminemia2/5 (40%) 2/18 (11.1%)
    Hypocalcemia2/5 (40%) 5/18 (27.8%)
    Hypoglycemia2/5 (40%) 0/18 (0%)
    Hypokalemia2/5 (40%) 5/18 (27.8%)
    Hypomagnesemia1/5 (20%) 0/18 (0%)
    Hyponatremia2/5 (40%) 5/18 (27.8%)
    Hypophosphatemia1/5 (20%) 6/18 (33.3%)
    Iron overload0/5 (0%) 1/18 (5.6%)
    Lymphocyte count decreased0/5 (0%) 3/18 (16.7%)
    Lymphocyte count increased0/5 (0%) 1/18 (5.6%)
    Hyperammonemia0/5 (0%) 1/18 (5.6%)
    Musculoskeletal and connective tissue disorders
    Back pain1/5 (20%) 1/18 (5.6%)
    Bone pain0/5 (0%) 1/18 (5.6%)
    Nervous system disorders
    Spasticity0/5 (0%) 1/18 (5.6%)
    Syncope0/5 (0%) 1/18 (5.6%)
    Respiratory, thoracic and mediastinal disorders
    Bronchopulmonary hemorrhage1/5 (20%) 0/18 (0%)
    Pleuritic pain0/5 (0%) 1/18 (5.6%)
    Pneumonitis0/5 (0%) 2/18 (11.1%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/TitleClinical Research Coordinator, Consortia
    OrganizationTherapeutic Advancements of Childhood Leukemia and Lymphoma
    Phone323-361-5312
    Emailrleong@chla.usc.edu
    Responsible Party:
    Therapeutic Advances in Childhood Leukemia Consortium
    ClinicalTrials.gov Identifier:
    NCT01483690
    Other Study ID Numbers:
    • T2009-003
    First Posted:
    Dec 1, 2011
    Last Update Posted:
    Oct 27, 2020
    Last Verified:
    Oct 1, 2020