NCCTG trial of gemcitabine for relapsed B-cell chronic lymphocytic leukemia

Abstract

6726 Background: Gemcitabine demonstrates in vitro activity against lymphoid cell lines, and has shown clinical responses in patients with non-Hodgkin's lymphoma. This study was performed to determine the efficacy and toxicity of gemcitabine in B-CLL patients with relapsed disease. Methods: Patients with relapsed B-CLL and prior treatment with both a purine nucleoside (fludarabine or cladribine) and an alkylating agent were enrolled. Treatment was with gemcitabine (1,000mg/m2) on days 1 and 8 of a 28-day cycle. A two-stage phase II trial design was used to assess the proportion of confirmed responses and toxicities. Results: 22 patients were enrolled. One patient withdrew prior to treatment and two were deemed ineligible, leaving 19 eligible patients. The median age was 63 years and median prior treatments were 3. The study was terminated at the interim analysis due to lack of efficacy, with only one patient having a partial response. Only 6 patients completed the protocol due to: disease progression (8), adverse reaction (3), alternative treatment (2), refusal (1), and death on study (1). Thirteen patients (68%) had stable disease as their best response. The median time to progression was 72 days. The most common hematologic toxicity was thrombocytopenia. The most common non-hematologic toxicity was infection. The death on study occurred in a patient with known heart disease who died of a myocardial infarction. Correlative laboratory studies indicated a high risk group of CLL patients entered this protocol. Fluorescent in situ hybridization detected the following chromosome abnormalities: 17p-(3), 11q-(5), +12(4), 13q-(5), polyploid (1), and normal (1). IgVH mutation status was able to be obtained in 9 patients, it was non-mutated in 7 and mutated in 2. Nine of the nineteen patients were CD38 positive. Conclusions: As a single agent gemcitabine did not show sufficient efficacy in a fludarabine or cladribine pretreated patient cohort of relapsed B cell CLL patients, who also expressed both adverse FISH anomalies and IgVH status. Whether it has a role in more chemotherapy naïve CLL patients, or in combination with other agents, remains to be determined. No significant financial relationships to disclose.