Topotecan in Treating Children With Refractory Leukemia

National Cancer Institute (NCI)

Status and phase

Completed

Phase 1

Conditions

Leukemia

Treatments

Drug: topotecan hydrochloride

Study type

Interventional

Funder types

NIH

Identifiers

NCT00002705

POG-9575

CDR0000064511 (Registry Identifier)

NCI-2012-01833

Details and patient eligibility

About

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.

Full description

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.

Enrollment

3 patients

Sex

All

Ages

Under 20 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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