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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
110
Locations
1
Arm
108
Anticipated Duration (Months)
1.5
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 Disease Intervention/Treatment Phase
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 :
Sep 29, 2025
Anticipated Study Completion Date :
Sep 29, 2025

Arms and Interventions

Arm Intervention/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

    Site City State Country Postal Code
    1 The Childrens Hospital of Alabama Birmingham Alabama United States 35233
    2 Phoenix Children'S Hospital Phoenix Arizona United States 85016
    3 Arkansas Childrens Hospital Little Rock Arkansas United States 72202
    4 Kaiser Permanente Fontana California United States 92335
    5 Loma Linda University Cancer Center Loma Linda California United States 92350
    6 Miller Childrens Hospital Pharmacy Long Beach California United States 90806
    7 Children'S Hospital Los Angeles Los Angeles California United States 90027
    8 Kaiser Foundation Health Plan Los Angeles California United States 90027
    9 Southern California Permanente Medical Group Los Angeles California United States 90027
    10 Valley Childrens Hospital Madera California United States 93636
    11 Choc Children Hospital Orange California United States 92868
    12 Lucille Packard Childrens Hospital Palo Alto California United States 94304
    13 Kaiser Permanente San Diego California United States 92111
    14 Rady Children'S Hospital - San Diego San Diego California United States 92123
    15 Ucsf Pediatric Oncology San Francisco California United States 94158
    16 Kaiser Permanente Downey Santa Fe Springs California United States 90670
    17 Children'S Hospital Colorado Aurora Colorado United States 80045
    18 Connecticut Children'S Medical Ctr Hartford Connecticut United States 06106
    19 Yale New Haven Hospital New Haven Connecticut United States 06510
    20 Alfred I Dupont Hospital For Wilmington Delaware United States 19803
    21 Childrens Hospital of Southwest Florida Fort Myers Florida United States 33908
    22 University of Florida Health Shands Hospital Gainesville Florida United States 32610
    23 Joe Dimaggio Children Hospital Hollywood Florida United States 33021
    24 Nemours Childrens Clinic Jacksonville Florida United States 32207
    25 Florida Hospital Orlando Orlando Florida United States 32803
    26 Arnold Palmer Hospital For Children Orlando Florida United States 32806
    27 Nemours Childrens Clinic Pensacola Florida United States 32504
    28 All Childrens Hospital Saint Petersburg Florida United States 33701
    29 Healthpoint Medical Group-Hematology Tampa Florida United States 33607
    30 Saint Marys Medical Center West Palm Beach Florida United States 33407
    31 Egleston Children'S Health Atlanta Georgia United States 30322
    32 Hawaii Pacific Health Research Insititution Honolulu Hawaii United States 96813
    33 Ann & Robert H. Lurie Children'S Hospital Chicago Illinois United States 60611
    34 Loyola University Medical Center Maywood Illinois United States 60153
    35 Southern Illinois University School of Medicine Springfield Illinois United States 62702
    36 Riley Hospital For Children Indianapolis Indiana United States 46202
    37 St Vincent Hospital Indianapolis Indiana United States 46260
    38 Blank Childrens Hospital Des Moines Iowa United States 50309
    39 University of Iowa Iowa City Iowa United States 52242
    40 University of Kentucky Department of Neurology Lexington Kentucky United States 40536
    41 Norton Cancer Institute Louisville Kentucky United States 40202
    42 Ochsner Clinic New Orleans Louisiana United States 70121
    43 Maine Center For Cancer Medicine Scarborough Maine United States 04074
    44 Sinai Hospital Cancer Institute Baltimore Maryland United States 21215
    45 Johns Hopkins University Baltimore Maryland United States 21287-7049
    46 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
    47 University of Michigan Cancer Center Ann Arbor Michigan United States 48109
    48 Grand Rapids Clinical Oncology Program Grand Rapids Michigan United States 49503
    49 Sparrow Cancer Center Grand Rounds Lansing Michigan United States 48912
    50 Children'S Hlth Care Mnpls Minneapolis Minnesota United States 55404
    51 University of Minnesota Minneapolis Minnesota United States 55454
    52 University of Mississippi Medical Center Jackson Mississippi United States 39216
    53 The Children'S Mercy Hospital Outpatient Kansas City Missouri United States 64108
    54 Washington University Saint Louis Missouri United States 63110
    55 Children'S Hospital & Medical Center Omaha Nebraska United States 68114
    56 Children'S Center For Cancer & Blood Dis Las Vegas Nevada United States 89109
    57 Hackensack University Medical Center Hackensack New Jersey United States 07601
    58 Regional Cancer Care Associates Llc (Rcca)- Morristown/Summit Medical Group Morristown New Jersey United States 07962
    59 Rutgers Cancer Institute of Nj New Brunswick New Jersey United States 08901
    60 Newark Beth Israel Medical Center Newark New Jersey United States 07112
    61 St Josephs Regional Medical Center Paterson New Jersey United States 07503
    62 University of New Mexico Hospital Albuquerque New Mexico United States 87131
    63 Albany Medical College Albany New York United States 12208
    64 Roswell Park Cancer Institute Buffalo New York United States 14263
    65 Steven & Alexandra Cohen Children'S Medi New Hyde Park New York United States 11040
    66 Columbia University Medical Center New York New York United States 10032
    67 Weill Medical College of Cornell University New York New York United States 10065
    68 University of Rochester Medical Center Rochester New York United States 14642
    69 Suny Upstate Medical University Syracuse New York United States 13210
    70 New York Medical College Valhalla New York United States 10595
    71 Lineberger Comprehensive Cancer Center At University of North Carolina Chapel Hill Chapel Hill North Carolina United States 27514
    72 Carolina Neurological Clinic Charlotte North Carolina United States 28203
    73 Wake Forest University Winston-Salem North Carolina United States 27157
    74 Akron Children'S Hospital Akron Ohio United States 44308
    75 Cincinnati Childrens Hospital Medical Center Cincinnati Ohio United States 45229
    76 Rainbow Babies & Children Hosp Cleveland Ohio United States 44106
    77 Cleveland Clinic Foundation Cleveland Ohio United States 44195
    78 Nationwide Children'S Hospital Columbus Ohio United States 43205
    79 Dayton Clinical Oncology Program Dayton Ohio United States 45420
    80 Toledo Hospital Toledo Ohio United States 43606
    81 University of Oklahoma Health Sciences Center Oklahoma City Oklahoma United States 73104
    82 Emanuel Hosp & Health Center Portland Oregon United States 97227
    83 Oregon Health & Science University Portland Oregon United States 97239
    84 Penn State Hershey Melanoma and Skin Cancer Center Hershey Pennsylvania United States 17033
    85 Children'S Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    86 Childrens Hospital of Pittsburgh Pittsburgh Pennsylvania United States 15224
    87 Rhode Island Hospital Providence Rhode Island United States 02903
    88 Medical University of South Carolina Charleston South Carolina United States 29425
    89 Vanderbilt University Medical Center Nashville Tennessee United States 37232
    90 Dell Childrens Medical Center of Central Texas Austin Texas United States 78723
    91 Driscoll Children'S Hospital Corpus Christi Texas United States 78411
    92 Medical City Dallas Hospital Dallas Texas United States 75230
    93 University of Texas Southwestern Medical Center Dallas Texas United States 75390
    94 El Paso Children'S Hospital Corporation El Paso Texas United States 79905
    95 Texas Childrens Hospital Houston Texas United States 77030
    96 University of Texas Health Science Cente San Antonio Texas United States 78229
    97 Primary Children'S Hospital Salt Lake City Utah United States 84113
    98 Children'S Hospital of the Norfolk Virginia United States 23507
    99 Seattle Children'S Hospital Seattle Washington United States 98105
    100 Providence Sacred Heart Medical Center & Children'S Hospital Spokane Washington United States 99204
    101 St Vincent Hospital Green Bay Wisconsin United States 54301
    102 Medical College of Wisconsin Milwaukee Wisconsin United States 53226
    103 Alberta'S Children Hospital Calgary Alberta Canada T3B 6A8
    104 Bc Children'S Hospital Vancouver British Columbia Canada V6G1R8
    105 The Hospital For Sick Children Toronto Ontario Canada 94611
    106 Chu Sainte-Justine Montreal Quebec Canada H3T 1C5
    107 McGill University Health Centre/Glen Site/Cedars Cancer Centre Montreal Quebec Canada H4A 3J1
    108 McMaster University Medical Centre Hamilton Canada L8V 5C2
    109 San Jorge Childrens Hospital San Juan Puerto Rico 00912
    110 University Pediatric Hospital San Juan Puerto Rico 00921

    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:
    Aug 15, 2022
    Last Verified:
    Aug 1, 2022
    Keywords provided by Incyte Corporation
    B-cell acute lymphoblastic leukemia (ALL)
    pediatric
    multi-agent chemotherapy
    JAK inhibitor
    Additional relevant MeSH terms:
    Leukemia
    Precursor Cell Lymphoblastic Leukemia-Lymphoma
    Leukemia, Lymphoid
    Leucovorin
    Cytarabine
    Dexamethasone
    Prednisone
    Cyclophosphamide
    Doxorubicin
    Methotrexate
    Vincristine
    Asparaginase
    Mercaptopurine
    Pegaspargase
    Thioguanine
    Levoleucovorin

    Study Results

    No Results Posted as of Aug 15, 2022