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

Unspecified Childhood Solid Tumor, Protocol Specific Clinical Trial

Official title: A Phase I Study of BMS-354825 (Dasatinib) in Children With Recurrent/Refractory Solid Tumors or Imatinib Resistant Ph+ Leukemia (BMS Trial CA180038)

Status Completed

Clinical Trial 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

Clinical Trial 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. ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Accelerated Phase Chronic Myelogenous Leukemia
• Blast Crisis
• Blastic Phase Chronic Myelogenous Leukemia
• Childhood Chronic Myelogenous Leukemia
• Chronic Myelogenous Leukemia, BCR-ABL1 Positive
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Meningeal Chronic Myelogenous Leukemia
• Philadelphia Chromosome
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Recurrent Childhood Acute Lymphoblastic Leukemia
• Relapsing Chronic Myelogenous Leukemia
• Unspecified Childhood Solid Tumor, Protocol Specific

• NCT number: NCT00316953
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Completed
• Phase: Phase 1
• Start date: March 2006