A phase II pilot efficacy trial of the combination regimen peg asparaginase/peg liposomal doxorubicin/dexamethasone (ODD) in patients with refractory lymphoid malignancies (NCT00837200).

Abstract

e19502 Background: Asparaginase is a mainstay of the treatment for ALL depriving the malignant cells of asparagine leading to cell death. There are reports of asparaginase activity in non-ALL malignancies including CLL, NHL, and multiple myeloma. We developed a combination regimen with full dose PEG-Asparagase (O) together with low dose liposomal doxorubin (D) and dexamethasone (D) (ODD regimen) as a non-myelotoxic regimen for pts with advanced lymphoid malignancies and impaired bone marrow function, hoping this novel approach of inducing asparaginine deficiency would translate into benefit. Methods: A phase II trial of ODD with the O given D1 and D15 at 2500 IU/m2, D given D1 and D15 as 20 mg/m2 and the Dex given as 20 mg D1, D8, D15 and D22 of a 28 day cycle was initiated. Pts with any non-ALL lymphoid malignancy were eligible if they had failed at least one prior standard regimen. The study had a Simon 2-stage design with Response Rate as the primary endpoint. Secondary endpoints were safety and correlation of asparginase levels with response/toxicity. Results: 13 pts enrolled of 16 screened of whom 12 were evaluable for response. These included 7 MM pts and 6 with diffuse large B-cell lymphoma. The pts were heavily pre-treated with 3 (range 1 to 8) median prior regimens. 6 of the13 pts were over 70 yrs. One pt progressed before one complete cycle was given so was not evaluable for response. 2 pts (both MM) had a response which was defined as Stable Disease > 2 months; the other 10 had Progressive Disease. One responding pt was later taken off for O-related toxicities (DVT/PE, elevated enzyme levels). Effective Asparaginase levels were obtained in the serum of most tested pts. In general, the regimen was well tolerated considering the advanced nature of these cases, but typical O related toxicities were observed. Conclusions: We conclude that the ODD regimen, although well tolerated, had little appreciable activity in this heavily pre-treated group of pts with refractory DLBCL and MM. Whether it would have meaningful activity in less advanced states of these diseases or other lymphoid neoplasms remains an open question. Clinical trial information: NCT00837200.