A phase I dose-escalation study of clofarabine in combination with fractionated gemtuzumab ozogamicin in patients with refractory or relapsed acute myeloid leukemia.

Clofarabine and gemtuzumab ozogamicin (GO) are active agents against acute myeloid leukemia (AML), but have not previously been tested in combination. We conducted a phase I study to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of clofarabine when combined with GO in adult patients with relapsed or refractory AML. Twenty patients received clofarabine (10, 20 or 30 mg/m(2)) on days 1-5, with GO 3 mg/m(2)/day on days 1, 4 and 7. Common dose-limiting toxicities were prolonged myelosuppression and hepatotoxicity. Clofarabine 20 mg/m(2) was the MTD, but with a DLT rate of 0.38 (5/13) - a rate that is prohibitively high to recommend for phase II study. The overall response rate (complete response [CR] + complete response with incomplete hematologic recovery [CRi]) was 42% among all patients. Thus, this combination demonstrated activity in relapsed and refractory patients, but further testing of the combination using lower doses of GO may identify more favorable rates of toxicity while maintaining efficacy.