Trial Information

TOPOTECAN FOR CHILDREN WITH REFRACTORY LEUKEMIA, A PEDIATRIC ONCOLOGY GROUP PHASE I COOPERATIVE AGREEMENT STUDY

OBJECTIVES:

I. Describe the qualitative and quantitative toxic effects, including acute and chronic
dose-limiting toxicity, cumulative toxicity, and time to recovery, in pediatric patients
with refractory leukemia who are treated with a 30-minute daily infusion of topotecan (TOPO)
for up to 12 consecutive days every 3 weeks.

II. Estimate the maximum tolerated dose of TOPO that results in tolerable, predictable, and
reversible toxicity.

III. Determine the precautions and supportive therapy that should be used and the clinical
and laboratory studies needed to monitor or alter therapy to prevent unacceptable toxicity
in these patients.

IV. Observe any antileukemic effects that may occur during this phase I study in which
duration of treatment is increased from 7 to 9 and then 12 days and TOPO doses are
escalated.

V. Determine the recommended phase II pediatric dose of TOPO. VI. Characterize the
pharmacokinetic parameters of TOPO and evaluate changes in these parameters with the first
and last doses to determine whether there is drug accumulation.

VII. Correlate, if possible, these pharmacokinetic parameters with clinical response and
toxicity.

OUTLINE:

Single-Agent Chemotherapy. Topotecan, TOPO, NSC-609699.