Immunotoxin in Treating Patients With Leukemia or Lymphoma

NCT ID: NCT00002765

RATIONALE: Immunotoxins can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. PURPOSE: Phase I trial to study the effectiveness of LMB-2 immunotoxin in treating patients who have leukemia or lymphoma.
OBJECTIVES: - Assess the therapeutic efficacy and toxicity of the recombinant immunotoxin LMB-2, an anti-Tac murine monoclonal antibody fragment conjugated to a truncated portion of Pseudomonas exotoxin, in patients with Tac-expressing leukemias and lymphomas. - Define the pharmacokinetics of LMB-2, including the terminal elimination serum half-life, area under the curve, and volume of distribution. - Evaluate, in a preliminary manner, the immunogenicity of LMB-2 in these patients. - Determine the effect of LMB-2 on various components of the circulating cellular immune system. OUTLINE: This is a dose escalation study. Patients receive LMB-2 immunotoxin IV over 30 minutes on days 1, 3, and 5. Treatment repeats every 15-21 days for up to 10 courses in the absence of disease progression, neutralizing antibodies, or unacceptable toxicity. Cohorts of 3-6 patients each receive escalating doses of LMB-2 immunotoxin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 patient experiences dose limiting toxicity. PROJECTED ACCRUAL: A maximum of 40 patients will be accrued for this study.
Leukemia, Lymphoma
recurrent adult Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, Waldenström macroglobulinemia, recurrent adult acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, relapsing chronic myelogenous leukemia, refractory chronic lymphocytic leukemia, refractory hairy cell leukemia, recurrent small lymphocytic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult Burkitt lymphoma, stage I adult T-cell leukemia/lymphoma, stage II adult T-cell leukemia/lymphoma, stage III adult T-cell leukemia/lymphoma, stage IV adult T-cell leukemia/lymphoma, recurrent adult T-cell leukemia/lymphoma, prolymphocytic leukemia, recurrent mantle cell lymphoma, stage IV mycosis fungoides/Sezary syndrome, recurrent mycosis fungoides/Sezary syndrome, recurrent marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Last Updated
27 Apr 2015
Official Link
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Kreitman RJ, Margulies I, Stetler-Stevenson M, Wang QC, FitzGerald DJ, Pastan I. Cytotoxic activity of disulfide-stabilized recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) toward fresh malignant cells from patients with B-cell leukemias. Clin Cancer Res. 2000 Apr;6(4):1476-87.

Robbins DH, Margulies I, Stetler-Stevenson M, Kreitman RJ. Hairy cell leukemia, a B-cell neoplasm that is particularly sensitive to the cytotoxic effect of anti-Tac(Fv)-PE38 (LMB-2). Clin Cancer Res. 2000 Feb;6(2):693-700.

Kreitman RJ, Wilson WH, White JD, Stetler-Stevenson M, Jaffe ES, Giardina S, Waldmann TA, Pastan I. Phase I trial of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) in patients with hematologic malignancies. J Clin Oncol. 2000 Apr;18(8):1622-36.

Kreitman RJ, Wilson WH, Robbins D, Margulies I, Stetler-Stevenson M, Waldmann TA, Pastan I. Responses in refractory hairy cell leukemia to a recombinant immunotoxin. Blood. 1999 Nov 15;94(10):3340-8.

United States