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

January 10, 2024 updated by: Incyte Corporation

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

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.

Study Overview

Study Type

Interventional

Enrollment (Actual)

171

Phase

  • Phase 2

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

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

Study Contact

  • Name: Incyte Corporation Call Center
  • Phone Number: 1.855.463.3463

Study Locations

      • Hamilton, Canada, L8V 5C2
        • McMaster University Medical Centre
    • Alberta
      • Calgary, Alberta, Canada, T3B 6A8
        • Alberta'S Children Hospital
    • British Columbia
      • Vancouver, British Columbia, Canada, V6G1R8
        • BC Children's Hospital
    • Ontario
      • Toronto, Ontario, Canada, 94611
        • The Hospital for Sick Children
    • Quebec
      • Montreal, Quebec, Canada, H3T 1C5
        • CHU Sainte-Justine
      • Montreal, Quebec, Canada, H4A 3J1
        • McGill University Health Centre/Glen Site/Cedars Cancer Centre
      • San Juan, Puerto Rico, 00912
        • San Jorge Childrens Hospital
      • San Juan, Puerto Rico, 00930
        • University Pediatric Hospital
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • The Childrens Hospital of Alabama
    • Arizona
      • Phoenix, Arizona, United States, 85016-7710
        • Phoenix CHildren's Hospital
    • Arkansas
      • Little Rock, Arkansas, United States, 72202
        • Arkansas Childrens Hospital
    • California
      • Fontana, California, United States, 92335
        • Kaiser Permanente
      • Loma Linda, California, United States, 92350
        • Loma Linda University Cancer Center
      • Long Beach, California, United States, 90806
        • Miller Childrens Hospital Pharmacy
      • Los Angeles, California, United States, 90027
        • Children's Hospital Los Angeles
      • Los Angeles, California, United States, 90027
        • Southern California Permanente Medical Group
      • Los Angeles, California, United States, 90027
        • Kaiser Foundation Health Plan
      • Madera, California, United States, 93636-8762
        • Valley Childrens Hospital
      • Orange, California, United States, 92868
        • Choc Children Hospital
      • Palo Alto, California, United States, 94304
        • Lucille Packard Childrens Hospital
      • San Diego, California, United States, 92123
        • Rady Children's Hospital - San Diego
      • San Diego, California, United States, 92111
        • Kaiser Permanente
      • San Francisco, California, United States, 94158
        • Ucsf Pediatric Oncology
      • Santa Fe Springs, California, United States, 90670
        • Kaiser Permanente Downey
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado
    • Connecticut
      • Hartford, Connecticut, United States, 06106
        • Connecticut Children'S Medical Ctr
      • New Haven, Connecticut, United States, 06510
        • Smilow Cancer Center - Yale
    • Delaware
      • Wilmington, Delaware, United States, 19803
        • Alfred I. DuPont Hospital for Children
    • Florida
      • Fort Myers, Florida, United States, 33908
        • Childrens Hospital of Southwest Florida
      • Hollywood, Florida, United States, 33021
        • Joe Dimaggio Children Hospital
      • Jacksonville, Florida, United States, 32207
        • Nemours Childrens Clinic
      • Jacksonville, Florida, United States, 32209
        • University of Florida Health Shands Hospital
      • Orlando, Florida, United States, 32803
        • Florida Hospital Orlando
      • Orlando, Florida, United States, 32806
        • Arnold Palmer Hospital for Children
      • Pensacola, Florida, United States, 32504
        • Nemours Childrens Clinic
      • Saint Petersburg, Florida, United States, 33701
        • All Childrens Hospital
      • Tampa, Florida, United States, 33607
        • St Josephs Childrens Hospital Tampa
      • West Palm Beach, Florida, United States, 33407
        • Saint Marys Medical Center
    • Georgia
      • Atlanta, Georgia, United States, 30322-1060
        • Egleston Children'S Health
    • Hawaii
      • Honolulu, Hawaii, United States, 96826
        • Kapiolani Medical Center for Women and Children
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Ann & Robert H. Lurie Children's Hospital
      • Maywood, Illinois, United States, 60153-3328
        • Loyola University Medical Center
      • Springfield, Illinois, United States, 62702
        • Southern Illinois University School of Medicine
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Riley Hospital for Children
      • Indianapolis, Indiana, United States, 46260
        • St Vincent Hospital
    • Iowa
      • Des Moines, Iowa, United States, 50309
        • Blank Childrens Hospital
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospital and Clinics
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky
      • Louisville, Kentucky, United States, 40202
        • Kosair Childrens Hospital
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Clinic
    • Maine
      • Scarborough, Maine, United States, 04074
        • Maine Center for Cancer Medicine
    • Maryland
      • Baltimore, Maryland, United States, 21215
        • Sinai Hospital of Baltimore
      • Baltimore, Maryland, United States, 21287-7049
        • Johns Hopkins University
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Boston Children'S
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Cs Mott Childrens Hospital
      • Grand Rapids, Michigan, United States, 49503
        • Helen Devos Childrens Hosp
      • Lansing, Michigan, United States, 48912
        • Michigan State University
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Children's Hospitals and Clinics of Minnesota
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • The Children'S Mercy Hospital Outpatient
      • Saint Louis, Missouri, United States, 63130
        • Washington University
    • Nebraska
      • Omaha, Nebraska, United States, 68114
        • Children's Hospital & Medical Center
    • Nevada
      • Las Vegas, Nevada, United States, 89109
        • Alliance for Childhood Diseases
      • Las Vegas, Nevada, United States, 89109
        • Children'S Center For Cancer & Blood Dis
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
      • Morristown, New Jersey, United States, 07962
        • Morristown Medical Center
      • New Brunswick, New Jersey, United States, 08901
        • Rutgers Cancer Institute of NJ
      • Newark, New Jersey, United States, 07112
        • Newark Beth Israel Medical Center
      • Paterson, New Jersey, United States, 07503
        • St Josephs Regional Medical Center
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • University of New Mexico Hospital
    • New York
      • Albany, New York, United States, 12208
        • Albany Medical College
      • Buffalo, New York, United States, 14263
        • Roswell Park Comprehensive Cancer Center
      • New Hyde Park, New York, United States, 11040
        • Cohen Children's Medical Center
      • New York, New York, United States, 10021
        • Weill Cornell Medical College
      • New York, New York, United States, 10032
        • Nyu Clinical Cancer Center
      • Rochester, New York, United States, 14642
        • University of Rochester Medical Center
      • Syracuse, New York, United States, 13210
        • SUNY Upstate Medical University
      • Valhalla, New York, United States, 10595
        • New York Medical College
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
        • University of North Carolina at Chapel Hill
      • Charlotte, North Carolina, United States, 28203
        • Carolinas Medical Center
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University
    • Ohio
      • Akron, Ohio, United States, 44308
        • Akron Children's Hospital
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Childrens Hospital Medical Center
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
      • Cleveland, Ohio, United States, 44106
        • Rainbow Babies & Children Hosp
      • Columbus, Ohio, United States, 43205
        • Nationwide Children's Hospital
      • Dayton, Ohio, United States, 45404
        • Dayton Children's Hospital
      • Toledo, Ohio, United States, 43606
        • Toledo Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Oregon
      • Portland, Oregon, United States, 97227
        • Legacy Emanuel Hospital and Health Center
      • Portland, Oregon, United States, 97239
        • Doernbecher Childrens Hospital
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033-2360
        • Penn State Hershey Medical Center
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15224
        • Childrens Hospital of Pittsburgh
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Hasbro Childrens Hospital
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center
    • Texas
      • Austin, Texas, United States, 78723
        • Dell Childrens Medical Center of Central Texas
      • Corpus Christi, Texas, United States, 78411
        • Driscoll Children's Hospital
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center
      • Dallas, Texas, United States, 75230
        • Medical City Dallas Hospital
      • El Paso, Texas, United States, 79905
        • El Paso Children'S Hospital Corporation
      • Houston, Texas, United States, 77030
        • Texas Childrens Hospital
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Science Cente
    • Utah
      • Salt Lake City, Utah, United States, 84113
        • Primary Children's Hospital
    • Virginia
      • Norfolk, Virginia, United States, 23507
        • Children'S Hospital of the
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital
      • Spokane, Washington, United States, 99204
        • Providence Sacred Heart Medical Center & Children's Hospital
    • Wisconsin
      • Green Bay, Wisconsin, United States, 54301
        • St Vincent Hospital
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College Of Wisconsin

Participation Criteria

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

Eligibility Criteria

Ages Eligible for Study

1 year to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Eligible for study when participant is 1 year to 21 years at the time of diagnosis
  • Eligible Ages in 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

Study Plan

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

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ruxolitinib in combination with chemotherapy
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Part 1: Safety/tolerability of ruxolitinib in combination with chemotherapy as measured by adverse events (AEs), vital signs, clinical laboratory tests, and echocardiograms
Time Frame: 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)
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)
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
Time Frame: Part 2: assessed at 3 years
Part 2: assessed at 3 years

Secondary Outcome Measures

Outcome Measure
Time Frame
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
Time Frame: 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)
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)

Collaborators and Investigators

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

Investigators

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

Study record dates

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

Study Major Dates

Study Start (Actual)

September 30, 2016

Primary Completion (Estimated)

February 1, 2026

Study Completion (Estimated)

February 1, 2026

Study Registration Dates

First Submitted

March 9, 2016

First Submitted That Met QC Criteria

March 24, 2016

First Posted (Estimated)

March 31, 2016

Study Record Updates

Last Update Posted (Actual)

January 12, 2024

Last Update Submitted That Met QC Criteria

January 10, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Other Study ID Numbers

  • INCB 18424-269
  • AALL1521 (Other Identifier: Children's Oncology Group)

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

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