INCB18424 in Treating Young Patients With Relapsed or Refractory Solid Tumor, Leukemia, or Myeloproliferative Disease
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.
Chronic Myeloproliferative Disorders
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: ruxolitinib phosphate
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of JAK Inhibition (INCB018424) in Children With Relapsed or Refractory Solid Tumors, Leukemias, and Myeloproliferative Neoplasms|
- Maximum-tolerated dose and/or recommended phase II dose [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
- Toxicity [ Time Frame: 30 days post treatment ] [ Designated as safety issue: Yes ]
- Pharmacokinetics [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
- Antitumor activity [ Time Frame: Up to 30 days post treatment ] [ Designated as safety issue: No ]
- Toxicity and biologic activity [ Time Frame: Day 1 and Day 15 ] [ Designated as safety issue: No ]
|Study Start Date:||September 2010|
|Estimated Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
|Experimental: Treatment (Ruxolitinib)||Drug: ruxolitinib phosphate Other: laboratory biomarker analysis Other: pharmacological study|
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01164163
Hide Study Locations
|United States, Alabama|
|UAB Comprehensive Cancer Center|
|Birmingham, Alabama, United States, 35294|
|United States, California|
|Children's Hospital of Orange County|
|Orange, California, United States, 92868|
|UCSF Helen Diller Family Comprehensive Cancer Center|
|San Francisco, California, United States, 94115|
|United States, Colorado|
|Children's Hospital Colorado Center for Cancer and Blood Disorders|
|Aurora, Colorado, United States, 80045|
|United States, District of Columbia|
|Children's National Medical Center|
|Washington, District of Columbia, United States, 20010-2970|
|United States, Georgia|
|AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus|
|Atlanta, Georgia, United States, 30322|
|United States, Illinois|
|Children's Memorial Hospital - Chicago|
|Chicago, Illinois, United States, 60611|
|United States, Indiana|
|Riley's Children Cancer Center at Riley Hospital for Children|
|Indianapolis, Indiana, United States, 46202|
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231-2410|
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office|
|Bethesda, Maryland, United States, 20892-1182|
|United States, Massachusetts|
|Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, Michigan|
|C.S. Mott Children's Hospital at University of Michigan Medical Center|
|Ann Arbor, Michigan, United States, 48109-0286|
|United States, Minnesota|
|Masonic Cancer Center at University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|United States, Missouri|
|Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis|
|St. Louis, Missouri, United States, 63110|
|United States, New York|
|Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center|
|New York, New York, United States, 10032|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229-3039|
|United States, Oregon|
|Knight Cancer Institute at Oregon Health and Science University|
|Portland, Oregon, United States, 97239-3098|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104|
|Children's Hospital of Pittsburgh of UPMC|
|Pittsburgh, Pennsylvania, United States, 15213|
|United States, Tennessee|
|St. Jude Children's Research Hospital|
|Memphis, Tennessee, United States, 38105|
|United States, Texas|
|Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas|
|Dallas, Texas, United States, 75390|
|Baylor University Medical Center - Houston|
|Houston, Texas, United States, 77030-2399|
|United States, Washington|
|Children's Hospital and Regional Medical Center - Seattle|
|Seattle, Washington, United States, 98105|
|United States, Wisconsin|
|Midwest Children's Cancer Center at Children's Hospital of Wisconsin|
|Milwaukee, Wisconsin, United States, 53226|
|Principal Investigator:||Mignon Loh, MD||University of California, San Francisco|