RATIONALE: INCB18424 (Ruxolitinib) may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase 1 clinical trial is studying the side effects and best dose of INCB18424 in treating young patients with relapsed or refractory solid tumor, leukemia, or myeloproliferative disease.
OBJECTIVES: Primary * 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. Secondary * 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
49
UAB Comprehensive Cancer Center
Birmingham, Alabama, United States
Children's Hospital of Orange County
Orange, California, United States
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States
Children's Hospital Colorado Center for Cancer and Blood Disorders
Aurora, Colorado, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Maximum-tolerated dose and/or recommended phase II dose
Time frame: 28 days
Toxicity
Time frame: 30 days post treatment
Pharmacokinetics
Time frame: Up to 28 days
Antitumor activity
Time frame: Up to 30 days post treatment
Toxicity and biologic activity
Time frame: Day 1 and Day 15
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AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
Atlanta, Georgia, United States
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States
Riley's Children Cancer Center at Riley Hospital for Children
Indianapolis, Indiana, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States
...and 14 more locations