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Keywords:

  • XL119;
  • rebeccamycin analog;
  • leukemia;
  • phase 1

Abstract

BACKGROUND.

XL119 is a water-soluble derivative of rebeccamycin with dose-dependent myelosuppression as dose-limiting toxicity in phase 1 studies of solid tumors. A phase 1 study was conducted to determine the maximum tolerated dose and toxicities of XL119 in patients with advanced myelodysplastic syndrome and relapsed or refractory acute leukemias.

METHODS.

Thirty-one patients were treated at 7 dose levels ranging from 140 to 260 mg/m2/daily times 5 in a 21-day cycle. Consenting patients had correlative biologic parameters studied.

RESULTS.

Dose-limiting toxicity was grade 3/4 mucositis. The recommended phase 2 dose in hematologic malignancies is 240 mg/m2/daily times 5 in a 21-day cycle. Clinically significant reduction in bone marrow blasts were seen in 5 patients and additional patients had reductions in peripheral blood blasts. However, the responses were transient. Changes of plasma vascular endothelial growth factor levels from Day 1 to Day 7 correlated negatively with changes in peripheral blood blasts from Day 1 to Day 7.

CONCLUSIONS.

Further assessment of XL119 in combination with other agents in patients with acute leukemias and high-risk myelodysplastic syndrome is warranted. Cancer 2008. Published 2008 by the American Cancer Society.