Topotecan in Treating Children With Refractory Leukemia

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

Phase I trial to study the effectiveness of topotecan in treating children with refractory leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

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.

DISEASE CHARACTERISTICS:

-Histologically or cytologically confirmed leukemia refractory to conventional therapy or for which no effective curative therapy exists

PATIENT CHARACTERISTICS:

• Age: Under 21
• Performance status: ECOG 0-2
• Life expectancy: At least 8 weeks
• Adequate platelet count and hemoglobin required (transfusion allowed)
• Bilirubin no greater than 1.5 mg/dL
• AST or ALT no greater than 2 times normal
• Creatinine less than 1.5 mg/dL
• Adequate nutritional status, e.g. higher than third percentile weight for height
• Albumin at least 3 g/dL
• No severe uncontrolled infection
• No pregnant women
• Effective contraception required of fertile women

PRIOR CONCURRENT THERAPY:

• At least 3 weeks since systemic chemotherapy (6 weeks since nitrosoureas)
• Recovered at least 3 months since bone marrow transplant (at least 6 months since total-body irradiation)
• No concurrent anticancer therapy
• No concurrent treatment studies