A PHASE-I TRIAL OF A SINGLE HIGH-DOSE OF IDARUBICIN COMBINED WITH HIGH-DOSE CYTARABINE AS INDUCTION THERAPY IN RELAPSED OR REFRACTORY ADULTPATIENTS WITH ACUTE LYMPHOBLASTIC-LEUKEMIA

Relapsed or refractory adult acute lymphoblastic leukemia (ALL) carrie s a grave prognosis. The most promising strategy for curing these pati ents is through re-induction chemotherapy followed by successful allog eneic transplant. We studied a new high-dose induction regimen in orde r to improve the outcome for these patients. Eighteen adult patients w ith relapsed/ refractory ALL were treated on a phase I study of high-d ose cytarabine combined with a single escalating dose of idarubicin. F ive patients had primary refractory disease and 13 were treated in ref ractory relapse. Nine patients (50%) had Ph+ ALL. The induction regime n was cytarabine 3 g/m(2)/day intravenously days 1-5 and idarubicin as a single intravenous dose on day 3. G-CSF 5 mu g/kg subcutaneously ev ery 12 h was started on day 7. The initial idarubicin dose was 20 mg/m (2) with dose escalations of 10 mg m(2). Cohorts of three patients wer e treated at each idarubicin dose level. Unacceptable toxicity was enc ountered at 50 mg/m(2) with one death from infection and one death fro m cardiotoxicity in a patient with significant prior anthracycline exp osure. There were no instances of grade 4 non-hematologic toxicity enc ountered at idarubicin doses of 20 mg/m(2), 30 mg/m(2), or 40 mg/m(2). The data suggest a dose-response relationship for increasing doses of idarubicin with 0/3 complete responses (CR) at 20 mg/m(2), 1/3 CR at 30 mg/m(2), and 7/12 (58%) CR at idarubicin doses greater than or equa l to 40 mg/m(2). We conclude that concomitant administration of cytara bine 3 g/m(2)/day x 5 and high-dose idarubicin at 40 mg/m(2) as a sing le dose on day 3 can be administered safely to patients with refractor y and relapsed ALL.