Phase II study of interleukin-4 in indolent B-cell non-Hodgkin lymphoma and B-cell chronic lymphocytic leukemia: a study of the Eastern Cooperative Oncology Group (E5Y92).

Recombinant interleukin (IL)-4, 5 µg/kg thrice weekly for 3 weeks followed by a 2-week rest period (1 cycle) was administered to 32 eligible previously treated B-cell chronic lymphocytic leukemia (7 patients) or low-grade B-cell lymphoma patients (25 patients). Two cycles were given before response was evaluated. IL-6 serum levels were evaluated before therapy in all patients and at 12 weeks on study in 7 patients. None of the chronic lymphocytic leukemia patients responded. A partial response was observed in 3 lymphoma patients of 1.2, 3.0, and 3.5 months' duration and stable disease (median 1.5 mo) was observed in another 7 lymphoma patients. The median survival from registration on study was 29.7 months with 7 patients alive at the time of analysis for a median follow-up of 72.8 months. Toxicity was generally mild with no grade 4 nonhematologic toxicity observed. Recombinant IL-4 treatment was well tolerated in this study but had minimal antitumor activity.

Induction of adaptive Anti-HER2/neu immune responses in a Phase 1B/2 trial of 2B1 bispecific murine monoclonal antibody in metastatic breast cancer (E3194): a trial coordinated by the Eastern Cooperative Oncology Group.

2B1 is a bispecific murine monoclonal antibody that binds to the extracellular domains of HER2/neu and FcgammaRIII. 2B1 efficiently promotes the lysis of tumor cells overexpressing HER2/neu by natural killer cells and mononuclear phagocytes that express the FcgammaRIII A isoform. Here, we report the results of E3194, a phase 1B/2 trial conducted by the Eastern Cooperative Oncology Group that employed 2B1 therapy in 20 women with metastatic breast cancer. The median age was 51 years. All but 1 patient had received prior chemotherapy. After the first dose, 3 of the initial 8 patients experienced dose-limiting toxicities that required dose-reduction. The nature of these dose-limiting toxicities resulted in a reduced dose from 2.5 mg/m/d to 1 mg/m/d in the remaining 12 patients. Objective antitumor responses were not seen. However, 2B1 therapy induced adaptive immune responses to both intracellular and extracellular domains of HER2/neu. Even though 2B1 antibody therapy did not show activity in metastatic breast cancer at the current administered doses, the ability of this antibody to induce detectable immune responses against an important tumor antigen has implications for understanding the mechanisms by which antibodies that mediate antibody-directed cellular cytotoxicity may exert their clinical antitumor effects.