A Phase II Study of Oral Topotecan in Children With Relapsed Acute Leukemia
A Phase II Study of Oral Topotecan in Children With Relapsed Acute Leukemia
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.
PURPOSE: Phase II trial to study the effectiveness of topotecan in treating children who have relapsed acute leukemia, acute myeloid leukemia, or blast phase chronic myelogenous leukemia.
OBJECTIVES: I. Determine the response rate of patients with relapsed acute lymphocytic leukemia, acute myeloid leukemia, or blastic phase chronic myelogenous leukemia treated with oral topotecan. II. Determine the toxic effects and pharmacokinetics of this regimen in these patients.
OUTLINE: Patients are stratified by disease type (acute lymphocytic leukemia vs acute myeloid leukemia). Patients receive oral topotecan once daily on days 1-21. Courses repeat every 28 days in the absence of blasts in the blood, M3 bone marrow, or unacceptable toxicity. Patients are followed every 6 months until death.
PROJECTED ACCRUAL: A total of 50 patients (25 per stratum) will be accrued for this study within 2 years.
DISEASE CHARACTERISTICS: Histologically proven relapsed acute lymphocytic leukemia, acute myeloid leukemia, or blastic phase chronic myelogenous leukemia Refractory to conventional therapy and other therapies of higher priority May have concurrent extramedullary relapse except for testicular relapse or other extramedullary sites that may require concurrent radiotherapy
PATIENT CHARACTERISTICS: Age: 21 and under Performance status: ECOG 0-2 Life expectancy: At least 2 months Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2.0 times normal SGOT or SGPT less than 5 times normal Renal: Creatinine no greater than 1.5 times normal Other: Able to take oral liquid medication No GI neuropathy No other condition that may affect absorption of drug No diabetes mellitus Not pregnant or nursing Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY: Biologic therapy: Prior bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT) allowed and recovered At least 2 weeks since prior cytokine therapy and recovered No concurrent immune modulator therapy No concurrent cytokines including interleukin-11, interleukin-2, and epoetin alfa Chemotherapy: At least 2 weeks since prior chemotherapy (4 weeks for nitrosoureas) and recovered No more than 3 prior chemotherapy regimens No other concurrent chemotherapy Endocrine therapy: No concurrent steroids Radiotherapy: No prior craniospinal radiotherapy Prior total body irradiation allowed as part of BMT or PBSCT and recovered Concurrent radiotherapy for localized painful lesions allowed Surgery: Not specified Other: No concurrent metoclopramide or cisapride to maintain motility or gastric emptying No concurrent H2 antagonists No concurrent proton pump inhibitors No concurrent antacids for gastritis, gastroesophageal reflux, or ulcers (gastric or duodenal) No antacid therapy for 6 hours before and for 90 minutes after topotecan administration