INCB18424 in Treating Young Patients With Relapsed or Refractory Solid Tumor, Leukemia, or Myeloproliferative Disease
Condition: Chronic Myeloproliferative Disorders; Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Unspecified Childhood Solid Tumor, Protocol Specific
MeSH terms: Neoplasms; Leukemia; Preleukemia; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): ruxolitinib phosphate; laboratory biomarker analysis; pharmacological study
Intervention type(s): Drug; Other; Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: unspecified childhood solid tumor, protocol specific; recurrent childhood acute lymphoblastic leukemia; recurrent childhood acute myeloid leukemia; refractory chronic lymphocytic leukemia; relapsing chronic myelogenous leukemia; childhood myelodysplastic syndromes; previously treated myelodysplastic syndromes; atypical chronic myeloid leukemia, BCR-ABL1 negative; chronic myelomonocytic leukemia; juvenile myelomonocytic leukemia; myelodysplastic/myeloproliferative neoplasm, unclassifiable; polycythemia vera; essential thrombocythemia; childhood acute promyelocytic leukemia (M3); acute myeloid leukemia/transient myeloproliferative disorder; primary myelofibrosis