Methods And Patients For Testing Bl22 In

BL22 was administered to 16 patients with HCL as part of a phase I trial in patients with B-cell malignancies.84 Like LMB-2, patients were dosed by 30-min infusion q.o.d. X 3. Patients without progressive disease or neutralizing antibodies to the toxin could be retreated at 3-week intervals. Disease was staged by blood counts with flow cytometry, bone marrow biopsy with immunohistochemistry, and computerized tomography. Neutralizing antibody and pharmacokinetic assays were performed by cytotoxicity assay as with LMB-2. Of 16 patients,84 13 had classic HCL and 3 had HCLv. As shown in Table 33.3, the median age was 54

years and the male-to-female ratio was 3/1, similar to what is reported for HCL.85 86 All patients were pre-treated with cladribine. Patients 5, 8, 9, 11, 13, and 14 were pretreated with one course, patients 4, 6, 10, 12, and 15 with two courses, patients 3, 7, and 16 with three courses, patient 1 with five courses, and patient 2 with six prior courses of cladribine. Patients often had one or several courses of prior interferon, pentostatin, and rituximab as well. About half the patients had prior splenectomy. Circulating HCL counts were typically high in patients after splenectomy but were highest (132,000/^L) in patient 4, who had a large spleen. All three HCLv patients (14, 18, and 26) had high circulating malignant counts. Dose levels included 3, 6, 10, 20, 30, 40, and 50 ^g/kg q.o.d. X 3, and patients often were retreated with a variety of different dose levels.

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