Dasatinib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia That Did Not Respond to Imatinib Mesylate
Condition: Accelerated Phase Chronic Myelogenous Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Childhood Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Meningeal Chronic Myelogenous Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Relapsing Chronic Myelogenous Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Blast Crisis; Leukemia, Myeloid, Accelerated Phase; Recurrence
Study type: Interventional
Phase: Phase 1

Summary: 
      This phase I trial is studying the side effects and best dose of dasatinib in treating young
      patients with recurrent or refractory solid tumors or Philadelphia chromosome-positive acute
      lymphoblastic leukemia or chronic myelogenous leukemia that did not respond to imatinib
      mesylate. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes
      needed for cell growth
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. Determine the toxicities and estimate the maximum tolerated dose or the recommended phase
      2 dose of dasatinib in pediatric patients with refractory solid tumors.

      II. Determine the toxicities of dasatinib in pediatric patients with imatinib
      mesylate-resistant Philadelphia chromosome-positive (Ph+) leukemia.

      III. Characterize the pharmacokinetics of dasatinib in pediatric patients with refractory
      solid tumors or imatinib-resistant Ph+ leukemia.

      SECONDARY OBJECTIVES:

      I. Preliminarily define the antitumor activity of dasatinib in pediatric patients with
      refractory solid tumors within the confines of a phase I study.

      II. Obtain pilot data on the activity of dasatinib administered in pediatric patients with
      Ph+ leukemia.

      III. Assess the biologic activity of dasatinib on tumor cells when available. IV. Determine
      the phosphotyrosine state of SRC and ABL substrates and correlate this with dasatinib dosage
      and antitumor activity (pharmacodynamics study).

      OUTLINE: This is a multicenter, dose-escalation study. Patients are stratified according to
      disease (solid tumors vs leukemia).

      Stratum 1 (solid tumors): Patients receive oral dasatinib twice daily on days 1-28. Treatment
      repeats every 28 days for up to 24 courses in the absence of disease progression or
      unacceptable toxicity.

      Cohorts of 3-6 patients receive escalating doses of dasatinib until the maximum tolerated
      dose (MTD) is determined. The MTD is defined as the dose preceding that at which ≥ 2 of 6
      patients experience dose-limiting toxicity (DLT).

      Stratum 2 (leukemia): Patients receive dasatinib as in stratum 1. Cohorts of 3-12 patients
      receive escalating or de-escalating doses of dasatinib. The MTD is defined as the dose
      preceding that at which 7 of 12 patients experience DLT.

      After completing study treatment, patients are followed for 1 month.
    

Intervention name(s): dasatinib; pharmacological study; laboratory biomarker analysis
Intervention type(s): Drug; Other; Other
Intervention description(s): Given orally; Correlative studies; Correlative studies
Other intervention name(s): BMS-354825; Sprycel; pharmacological studies
Intervention MeSH terms: Dasatinib
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment