A Phase I Study of JAK Inhibition (INCB018424) in Children With Relapsed or Refractory Solid Tumors, Leukemias, and Myeloproliferative Neoplasms
- To estimate the maximum-tolerated dose and/or recommended phase II dose of oral JAK
inhibitor INCB18424 administered continuously, twice daily to pediatric patients with
relapsed or refractory solid tumors.
- To define and describe the toxicities of this treatment administered on this schedule
in pediatric patients with relapsed or refractory solid tumors, leukemias, or
myeloproliferative neoplasms (MPNs).
- To characterize the pharmacokinetics of this treatment in pediatric patients with
relapsed or refractory solid tumors, leukemias, or MPNs.
- To preliminarily define the antitumor activity of this treatment within the confines of
a phase I study.
- To assess the biologic activity of oral JAK inhibitor INCB18424 upon JAK-STAT signaling
in pediatric patients with relapsed or refractory solid tumors, leukemias, or MPNs.
- To assess the cytotoxicity and biologic activity of oral JAK inhibitor INCB18424 upon
phosphosignaling and mutation burden in pediatric patients whose leukemias or MPNs have
known CRLF2 and/or JAK mutations.
OUTLINE: This is a multicenter, dose-escalation study.
Patients receive oral JAK inhibitor INCB18424 twice daily on days 1-28. Courses repeat every
28 days in the absence of disease progression or unacceptable toxicity.
Patients with relapsed or refractory leukemia may receive intrathecal chemotherapy in course
2 and subsequent courses at the discretion of the treating physician.
Plasma, bone marrow, and blood samples may be collected at baseline, during course 1, and
before subsequent courses for pharmacokinetic analysis and correlative biology studies.
After completion of study treatment, patients are followed up for 30 days.
Primary Purpose: Treatment
Maximum-tolerated dose and/or recommended phase II dose
Mignon Loh, MD
University of California, San Francisco
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|
|Children's Hospital of Orange County||Orange, California 92668|
|Children's National Medical Center||Washington, District of Columbia 20010-2970|
|Children's Hospital and Regional Medical Center - Seattle||Seattle, Washington 98105|
|Children's Memorial Hospital - Chicago||Chicago, Illinois 60614|
|St. Jude Children's Research Hospital||Memphis, Tennessee 38105-2794|
|Midwest Children's Cancer Center at Children's Hospital of Wisconsin||Milwaukee, Wisconsin 53226|
|Cincinnati Children's Hospital Medical Center||Cincinnati, Ohio 45229-3039|
|Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas||Dallas, Texas 75390|
|Baylor University Medical Center - Houston||Houston, Texas 77030-2399|
|UCSF Helen Diller Family Comprehensive Cancer Center||San Francisco, California 94115|
|AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus||Atlanta, Georgia 30322|
|Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|C.S. Mott Children's Hospital at University of Michigan Medical Center||Ann Arbor, Michigan 48109-0286|
|Masonic Cancer Center at University of Minnesota||Minneapolis, Minnesota 55455|
|Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis||St. Louis, Missouri 63110|
|Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center||New York, New York 10032|
|Knight Cancer Institute at Oregon Health and Science University||Portland, Oregon 97239-3098|
|Children's Hospital of Pittsburgh of UPMC||Pittsburgh, Pennsylvania 15213|
|Riley's Children Cancer Center at Riley Hospital for Children||Indianapolis, Indiana 46202-5225|
|UAB Comprehensive Cancer Center||Birmingham, Alabama 35294|
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office||Bethesda, Maryland 20892-1182|
|Children's Hospital Colorado Center for Cancer and Blood Disorders||Aurora, Colorado 80045|