Phase II study of cladribine (2-chlorodeoxyadenosine) in relapsed or refractory adult T-cell leukemia-lymphoma.

Abstract

Adult T-cell leukemia-lymphoma (ATL) is a retrovirus-associated T-cell malignancy with an extremely poor prognosis; the median survival time of ATL patients with the acute or lymphoma type is less than 1 year with various combination chemotherapies. Cladribine (2-chlorodeoxyadenosine; 2-CdA), a purine analog resistant to degradation by adenosine deaminase, has shown definitive clinical activity against various lymphoid malignancies, including hairy cell leukemia, indolent lymphoma, and cutaneous T-cell lymphoma. An in vitro study showed the sensitivity of T-lymphoblastoid cell lines to cladribine, and a preceding Japanese phase I study of cladribine showed that 1 refractory patient with ATL achieved an objective response. To evaluate the therapeutic efficacy of cladribine in treating ATL, we conducted a multicenter phase II study. The plan was to administer cladribine to 30 ATL patients as 0.09 mg/kg per day by 7-day continuous intravenous infusion every 4 weeks for up to 3 courses. Before the planned interim analysis, 16 patients with relapsed or refractory ATL were enrolled, 15 of whom were eligible. Only 1 of the 15 eligible patients showed an objective response (overall response rate, 7%; 90% confidence interval, 0% to 28%), and 11 patients (73%) showed progressive disease, mostly during the first course of treatment. Because the upper limit of the 90% confidence interval of the overall response rate did not reach 30% in the interim analysis, the Independent Monitoring Committee advised us to discontinue patient enrollment. In conclusion, cladribine is not worthy of further investigation for the treatment of ATL.

• Authors: Kensei Tobinai, Naokuni Uike, Yoshio Saburi, Takaaki Chou, Tetsuya Etoh, Masato Masuda, Fumio Kawano, Masao Matsuoka, Hirokuni Taguchi, Torahiko Makino, Yoshinobu Asano, Kazuo Tamura, Yasuo Ohashi, Cladribine/ATL Study Group, Japan
• Journal: International journal of hematology (Int J Hematol) Vol. 77 Issue 5 Pg. 512-7 (Jun 2003) ISSN: 0925-5710 [Print] Japan
• PMID: 12841391 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Cladribine

Topics

• Adult
• Aged
• Antineoplastic Agents (administration & dosage, toxicity)
• Cladribine (administration & dosage, toxicity)
• Disease Progression
• Female
• Humans
• Leukemia-Lymphoma, Adult T-Cell (complications, drug therapy)
• Male
• Middle Aged
• Remission Induction
• Salvage Therapy (methods)
• Treatment Failure