A Phase 2 Study of Ruxolitinib With Chemotherapy in Children With Acute Lymphoblastic Leukemia

Sponsor
Incyte Corporation (Industry)
Overall Status
Recruiting
CT.gov ID
NCT02723994
Collaborator
Children's Oncology Group (Other)
170
Enrollment
108
Locations
1
Arm
99
Anticipated Duration (Months)
1.6
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a nonrandomized study of ruxolitinib in combination with a standard multi-agent chemotherapy regimen for the treatment of B-cell acute lymphoblastic leukemia. Part 1 of the study will optimize the dose of study drug (ruxolitinib) in combination with the chemotherapy regimen. Part 2 will evaluate the efficacy of combination chemotherapy and ruxolitinib at the recommended dose determined in Part 1.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
170 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2 Study of the JAK1/JAK2 Inhibitor Ruxolitinib With Chemotherapy in Children With De Novo High-Risk CRLF2-Rearranged and/or JAK Pathway-Mutant Acute Lymphoblastic Leukemia
Actual Study Start Date :
Sep 30, 2016
Anticipated Primary Completion Date :
Dec 30, 2024
Anticipated Study Completion Date :
Dec 30, 2024

Arms and Interventions

ArmIntervention/Treatment
Experimental: Ruxolitinib in combination with chemotherapy

Drug: Ruxolitinib
In Part 1, ruxolitinib will be administered at a protocol-defined starting dose in combination with chemotherapy, with dose escalation and de-escalation following the rolling 6 study design. The established recommended starting dose will be taken forward into Part 2.
Other Names:
  • INCB018424
  • Drug: Asparaginase Erwinia Chrysanthemi

    Drug: Cyclophosphamide

    Drug: Cytarabine

    Drug: Dexamethasone

    Drug: Doxorubicin

    Drug: Leucovorin Calcium

    Drug: Mercaptopurine

    Drug: Methotrexate

    Drug: Pegaspargase

    Drug: Prednisone

    Drug: Thioguanine

    Drug: Vincristine Sulfate

    Outcome Measures

    Primary Outcome Measures

    1. Part 1: Safety/tolerability of ruxolitinib in combination with chemotherapy as measured by adverse events (AEs), vital signs, clinical laboratory tests, and echocardiograms [Part 1: AEs assessed from screening through up to 30 days after the last dose of study drug, expected to be 26 months (females) or 38 months (males)]

    2. Part 2: Efficacy of ruxolitinib in combination with chemotherapy as measured by Event-free survival, defined as the percentage of patients alive without relapse, progression, or death at 3 years from study Day 1 [Part 2: assessed at 3 years]

    Secondary Outcome Measures

    1. Safety and tolerability of the combination treatment for subjects beginning treatment at the recommended dose for Part 2, as assessed by AEs, vital signs, clinical laboratory tests, and echocardiograms [AEs assessed from screening through up to 30 days after the last dose of study treatment, expected to be 26 months (females) or 38 months (males)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    1 Year to 21 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Eligible for study when participant is 1 year to 21 years at the time of diagnosis

    • Eligible Ages in Australia and Canada; 2 years to 21 years

    • De novo high-risk (HR) Ph-like B-ALL for which any of following criteria are present at diagnosis:

    • Age ≥ 10 years

    • White blood cell (WBC) ≥ 50 × 10^3/μL

    • CNS3 leukemia at diagnosis

    • Systemic steroid pretreatment without presteroid WBC documentation

    • Diagnostic bone marrow or peripheral blood sample must have gene expression profiling and downstream genetic testing performed by submitting diagnostic specimens under the COG AALL08B1 or APEC14B1 biology studies, or AALL1131 or its successor study. Specimens must demonstrate a Ph-like expression profile (ie, LDA-positive) as tested by low density microarray testing at the COG ALL reference laboratory or TriCore laboratory at the University of New Mexico AND must contain 1 of the following genetic lesions: (determined at COG ALL reference laboratories, or equivalent

    CAP/CLIA-certified laboratories approved by the medical monitor:
    1. CRLF2 rearrangement* with confirmed JAK1 or JAK2 mutation (JAK+)

    2. CRLF2 rearrangement* without JAK mutation

    3. Other JAK pathway alterations (eg, JAK2 fusions, EPOR fusions, SH2B3 deletions, IL7RA mutations) with or without CRLF2-R, or CRLF2-R with unknown JAK status*† as determined by a COG ALL Reference Laboratory

    • Completed a 4-drug Induction therapy regimen (modified aBFM regimen or equivalent) in Study AALL1131 or its successor study, or as per the institutional standard of care for HR B-ALL and have had end-Induction minimal residual disease (MRD) assessed

    • Male and female subjects of reproductive non childbearing potential or willing to take appropriate precautions to avoid pregnancy or fathering a child for the duration of study participation

    Exclusion Criteria:
    • Receipt of any other cytotoxic chemotherapy before Induction therapy, with exception of hydroxyurea or steroid pretreatment

    • Trisomy 21 (Down syndrome)

    • BCR-ABL1-rearranged (Ph+) ALL

    • Calculated creatinine clearance or radioisotope glomerular filtration rate < 70 mL/min/1.73 m^2

    • Alanine aminotransferase ≥ 5 × upper limit of normal (ULN) for age

    • Direct bilirubin ≥ 1.5 × ULN (may be assumed if total bilirubin is below ULN)

    • History or evidence of cirrhosis

    • Platelet count < 75 × 10^3/μL

    • Absolute neutrophil count (ANC) < 750/μL

    • Positive screen for hepatitis B or C

    • Known human immunodeficiency virus infection

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Uab Dept of PediatricsBirminghamAlabamaUnited States35233
    2Phoenix Children'S HospitalPhoenixArizonaUnited States85016
    3Arkansas Childrens HospitalLittle RockArkansasUnited States72202
    4Kaiser PermanenteFontanaCaliforniaUnited States92335
    5Loma Linda University Cancer CenterLoma LindaCaliforniaUnited States92350
    6Miller Childrens Hospital PharmacyLong BeachCaliforniaUnited States90806
    7Kaiser Foundation Health PlanLos AngelesCaliforniaUnited States90027
    8Valley Childrens HospitalMaderaCaliforniaUnited States93636
    9Choc Children HospitalOrangeCaliforniaUnited States92868
    10Lucille Packard Childrens HospitalPalo AltoCaliforniaUnited States94304
    11Kaiser PermanenteSan DiegoCaliforniaUnited States92111
    12Rady Children'S Hospital - San DiegoSan DiegoCaliforniaUnited States92123
    13Ucsf Medical Center BenioffSan FranciscoCaliforniaUnited States94158
    14Kaiser Permanente DowneySanta Fe SpringsCaliforniaUnited States90670
    15Children'S Hospital ColoradoAuroraColoradoUnited States80045
    16Connecticut Children'S Medical CtrHartfordConnecticutUnited States06106
    17Yale New Haven HospitalNew HavenConnecticutUnited States06510
    18Alfred I Dupont Hospital ForWilmingtonDelawareUnited States19803
    19Childrens Hospital of Southwest FloridaFort MyersFloridaUnited States33908
    20University of Florida Health Shands HospitalGainesvilleFloridaUnited States32610
    21Joe Dimaggio Children HospitalHollywoodFloridaUnited States33021
    22Nemours Childrens ClinicJacksonvilleFloridaUnited States32207
    23Florida Hospital OrlandoOrlandoFloridaUnited States32803
    24Arnold Palmer Hospital For ChildrenOrlandoFloridaUnited States32806
    25Nemours Childrens ClinicPensacolaFloridaUnited States32504
    26All Childrens HospitalSaint PetersburgFloridaUnited States33701
    27Healthpoint Medical Group-HematologyTampaFloridaUnited States33607
    28St Marys Medical CenterWest Palm BeachFloridaUnited States33407
    29Egleston Children'S HealthAtlantaGeorgiaUnited States30322
    30Hawaii Pacific Health Research InsititutionHonoluluHawaiiUnited States96813
    31Ann & Robert H. Lurie Children'S HospitaChicagoIllinoisUnited States60611
    32Loyola University Medical CenterMaywoodIllinoisUnited States60153
    33Southern Illinois University School of MedicineSpringfieldIllinoisUnited States62702
    34Riley Hospital For Children At Iu HealthIndianapolisIndianaUnited States46202
    35St Vincent HospitalIndianapolisIndianaUnited States46260
    36Blank Childrens HospitalDes MoinesIowaUnited States50309
    37University of IowaIowa CityIowaUnited States52242
    38University of Kentucky Department of NeurologyLexingtonKentuckyUnited States40536
    39Norton Cancer InstituteLouisvilleKentuckyUnited States40202
    40Ochsner ClinicNew OrleansLouisianaUnited States70121
    41Maine Center For Cancer MedicineScarboroughMaineUnited States04074
    42Sinai Hospital Cancer InstituteBaltimoreMarylandUnited States21215
    43Johns Hopkins Medicine - the Sidney Kimmel Comprehensive Cancer CenterBaltimoreMarylandUnited States21287
    44Dana-Farber Cancer InstituteBostonMassachusettsUnited States02215
    45University of Michigan Cancer CenterAnn ArborMichiganUnited States48109
    46Grand Rapids Clinical Oncology ProgramGrand RapidsMichiganUnited States49503
    47Sparrow Cancer Center Grand RoundsLansingMichiganUnited States48912
    48Children'S Hlth Care MnplsMinneapolisMinnesotaUnited States55404
    49University of Minnesota, Masonic Cancer CenterMinneapolisMinnesotaUnited States55455
    50University of Mississippi Medical CenterJacksonMississippiUnited States39216
    51The Children'S Mercy Hospital OutpatientKansas CityMissouriUnited States64108
    52Washington University School of MedicineSaint LouisMissouriUnited States63130
    53Children'S Hospital & Medical CenterOmahaNebraskaUnited States68114
    54Children'S Center For Cancer & Blood DisLas VegasNevadaUnited States89109
    55Hackensack University Medical CenterHackensackNew JerseyUnited States07601
    56Regional Cancer Care Associates Llc (Rcca)- Morristown/Summit Medical GroupMorristownNew JerseyUnited States07962
    57Rutgers Cancer Institute of NjNew BrunswickNew JerseyUnited States08901
    58Newark Beth Israel Medical CenterNewarkNew JerseyUnited States07112
    59St Josephs Regional Medical CenterPatersonNew JerseyUnited States07503
    60University of New Mexico HospitalAlbuquerqueNew MexicoUnited States87131
    61Albany Medical CollegeAlbanyNew YorkUnited States12208
    62Roswell Park Cancer InstituteBuffaloNew YorkUnited States14263
    63Steven & Alexandra Cohen Children'S MediNew Hyde ParkNew YorkUnited States11040
    64Columbia University Medical CenterNew YorkNew YorkUnited States10032
    65Weill Medical College of Cornell UniversityNew YorkNew YorkUnited States10065
    66University of Rochester Medical CenterRochesterNew YorkUnited States14642
    67Suny Upstate Medical UniversitySyracuseNew YorkUnited States13210
    68New York Medical CollegeValhallaNew YorkUnited States10595
    69Lineberger Comprehensive Cancer Center At University of North Carolina Chapel HillChapel HillNorth CarolinaUnited States27514
    70Carolina Neurological ClinicCharlotteNorth CarolinaUnited States28203
    71Wake Forest UniversityWinston-SalemNorth CarolinaUnited States27157
    72Akron Children'S HospitalAkronOhioUnited States44308
    73Cincinnati Childrens Hospital Medical CenterCincinnatiOhioUnited States45229
    74Rainbow Babies & Children HospClevelandOhioUnited States44106
    75Cleveland Clinic Cancer Ctr R40ClevelandOhioUnited States44195
    76Nationwide Children'S HospitalColumbusOhioUnited States43205
    77Dayton Clinical Oncology ProgramDaytonOhioUnited States45420
    78Toledo HospitalToledoOhioUnited States43606
    79University of Oklahoma Health Sciences CenterOklahoma CityOklahomaUnited States73104
    80Emanuel Hosp & Health CenterPortlandOregonUnited States97227
    81Oregon Health & Science UniversityPortlandOregonUnited States97239
    82Penn State Hershey Melanoma and Skin Cancer CenterHersheyPennsylvaniaUnited States17033
    83Children'S Hospital of PhiladelphiaPhiladelphiaPennsylvaniaUnited States19104
    84Childrens Hospital of PittsburghPittsburghPennsylvaniaUnited States15224
    85Rhode Island HospitalProvidenceRhode IslandUnited States02903
    86Medical University of South CarolinaCharlestonSouth CarolinaUnited States29425
    87Vanderbilt-Ingram Cancer CenterNashvilleTennesseeUnited States37232
    88Dell Childrens Medical Center of Central TexasAustinTexasUnited States78723
    89Driscoll Children'S HospitalCorpus ChristiTexasUnited States78411
    90Texas Oncology - Medical City DallasDallasTexasUnited States75230
    91University of Texas Southwestern Medical CenterDallasTexasUnited States75390
    92El Paso Children'S Hospital CorporationEl PasoTexasUnited States79905
    93Texas Childrens HospitalHoustonTexasUnited States77030
    94University of Texas Health Science CenteSan AntonioTexasUnited States78229
    95Primary Children'S HospitalSalt Lake CityUtahUnited States84113
    96Children'S Hospital of theNorfolkVirginiaUnited States23507
    97Seattle Children'S HospitalSeattleWashingtonUnited States98105
    98Providence Sacred Heart Medical Center & Children'S HospitalSpokaneWashingtonUnited States99204
    99St Vincent HospitalGreen BayWisconsinUnited States54301
    100Medical College of WisconsinMilwaukeeWisconsinUnited States53226
    101Alberta'S Children HospitalCalgaryAlbertaCanadaT3B 6A8
    102Bc Children'S HospitalVancouverBritish ColumbiaCanadaV6G1R8
    103The Hospital For Sick ChildrenTorontoOntarioCanada94611
    104Chu Sainte-JustineMontrealQuebecCanadaH3T 1C5
    105McGill University Health Centre/Glen Site/Cedars Cancer CentreMontrealQuebecCanadaH4A 3J1
    106McMaster University Medical CentreHamiltonCanadaL8V 5C2
    107San Jorge Childrens HospitalSan JuanPuerto Rico00912
    108University Pediatric HospitalSan JuanPuerto Rico00921

    Sponsors and Collaborators

    • Incyte Corporation
    • Children's Oncology Group

    Investigators

    • Study Director: Albert Assad, MD, Incyte Corporation
    • Study Chair: Sarah Tasian, MD, Children's Hospital of Philadelphia, Philadelphia, PA

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Incyte Corporation
    ClinicalTrials.gov Identifier:
    NCT02723994
    Other Study ID Numbers:
    • INCB 18424-269
    • AALL1521
    First Posted:
    Mar 31, 2016
    Last Update Posted:
    Feb 24, 2022
    Last Verified:
    Feb 1, 2022

    Study Results

    No Results Posted as of Feb 24, 2022