lmb-2 immunotoxin in treating young patients with relapsed or refractory leukemia or lymphoma

Conditions: Leukemia; Lymphoma

Summary: rationale: lmb-2 immunotoxin can locate cancer cells and kill them without harming normal cells. purpose: this phase i trial is studying the side effects and best dose of lmb-2 immunotoxin in treating young patients with relapsed or refractory leukemia or lymphoma.

objectives: primary * determine the maximum tolerated dose of lmb-2 immunotoxin in pediatric patients with cd-25 positive relapsed or refractory leukemia or lymphoma. * determine the toxic effects of this drug in these patients. * determine the pharmacokinetics of this drug, including the terminal elimination serum half-life, area under the curve, volume of distribution, and relationship to disease burden, in these patients. secondary * evaluate the immonogenicity of this drug in these patients. * determine response in patients treated with this drug. * determine changes in lymphocyte subsets, immunoglobulin levels, serum cytokines, and soluble cytokine receptor levels in patients treated with this drug. outline: this is a dose-escalation, multicenter study. patients receive lmb-2 immunotoxin iv over 30 minutes on days 1, 3, and 5. treatment repeats every 28 days for up to 6 courses in the absence of disease progression, neutralizing antibodies (i.e., \> 75% of the activity of 1 µg/ml of lmb-2 immunotoxin), or unacceptable toxicity. patients achieving complete remission (cr) receive 2 additional courses beyond cr. patients with acute lymphoblastic leukemia also receive cytarabine and hydrocortisone intrathecally once monthly concurrent with restaging lumbar punctures. cohorts of 3-6 patients receive escalating doses of lmb-2 immunotoxin until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. once the mtd is determined, a total of 12 patients are treated at that dose level. patients are followed weekly for 1 month and then monthly thereafter. projected accrual: a total of 20-40 patients will be accrued for this study within 2-4 years.

Eligibility criteria:
disease characteristics: * histologically confirmed diagnosis of 1 of the following: * non-hodgkin's lymphoma, including the following subtypes: * lymphoblastic lymphoma * burkitt's lymphoma * large cell lymphoma * adult t-cell leukemia/lymphoma * cutaneous t-cell lymphoma * peripheral t-cell lymphoma * hodgkin's disease * acute myeloid leukemia * chronic myelogenous leukemia * acute lymphoblastic leukemia (all) * more than 5% blasts in the bone marrow (i.e., m2 marrow classification) * acute hybrid leukemia, including the following subtypes: * mixed lineage leukemia * biphenotypic leukemia * undifferentiated leukemia * cd25-positive (cd25+) disease, meeting 1 of the following criteria: * more than 15% of malignant cells are cd25+ by immunohistochemistry with anti-cd25 antibody * more than 30% of malignant cells from a site are cd25+ by fluorescence-activated cell sorting analysis * measurable or evaluable disease * relapsed or refractory disease after at least 1 standard chemotherapy regimen and 1 salvage regimen * no available alternative curative therapies * ineligible for or refused hematopoietic stem cell transplantation or disease activity that prohibits the required time to identify a suitable stem cell donor * no cns leukemia or lymphoma, as evidenced by any of the following criteria: * cerebrospinal fluid (csf) wbc \> 5/µl and confirmation of csf blasts * cranial neuropathies secondary to underlying malignancy * cns lymphoma detected by radiological imaging * prior cns involvement with no current evidence of cns malignancy allowed * no isolated testicular all patient characteristics: age * 6 months to 21 years performance status * ecog 0-3 (≥ 12 years of age) * lansky 40-100% (\< 12 years of age) life expectancy * not specified hematopoietic * pancytopenia due to disease allowed * for patients without bone marrow involvement: * absolute neutrophil count \> 1,000/mm\^3 * platelet count \> 50,000/mm\^3 (transfusion independent) hepatic * bilirubin ≤ 2.0 mg/dl * ast and alt ≤ 5 times upper limit of normal * hepatitis b surface antigen negative * hepatitis c antibody negative renal * creatinine clearance ≥ 60 ml/min or * creatinine, meeting the following age-related criteria: * ≤ 0.8 mg/dl (≤ 5 years of age) * ≤ 1.0 mg/dl (6 to 10 years of age) * ≤ 1.2 mg/dl (11 to 15 years of age) * ≤ 1.5 mg/dl (\> 15 years of age) * calcium 2.0-2.9 mmol/l cardiovascular * ejection fraction ≥ 45% by muga or * shortening fraction ≥ 28% by echocardiogram pulmonary * oxygen saturation ≥ 90% other * sodium 130-150 mmol/l * potassium 3.0-5.5 mmol/l * magnesium 0.5-1.23 mmol/l * hiv negative * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no clinically significant unrelated systemic illness that would preclude study participation * no conditions that would preclude study compliance * no serum that neutralizes \> 75% of the activity of 1 μg/ml of lmb-2 immunotoxin in tissue culture (due to either anti-toxin or anti-mouse immunoglobulin g antibodies) * no active graft-vs-host disease (i.e., off immunosuppression) prior concurrent therapy: biologic therapy * prior autologous bone marrow transplantation (bmt) allowed * at least 100 days since prior allogeneic bmt * at least 1 week since prior colony-stimulating factors (e.g., filgrastim \[g-csf\], sargramostim \[gm-csf\], or epoetin alfa) chemotherapy * at least 2 weeks since prior chemotherapy (4 weeks for nitrosoureas) except intrathecal chemotherapy * no other concurrent chemotherapy endocrine therapy * concurrent corticosteroids allowed provided the dose has been stable for the past week and does not increase during study treatment * tapering or discontinuation of steroids allowed radiotherapy * at least 3 weeks since prior radiotherapy unless \< 10% of marrow is irradiated and measurable disease exists outside the radiation port surgery * not specified other * recovered from all prior therapy * at least 30 days since prior investigational agents * concurrent oral supplementation to maintain normal electrolyte levels allowed * no concurrent anticoagulation therapy for disease-related conditions * no other concurrent investigational agents

Keywords: recurrent adult t-cell leukemia/lymphoma recurrent childhood acute lymphoblastic leukemia childhood burkitt lymphoma recurrent childhood acute myeloid leukemia recurrent childhood large cell lymphoma recurrent childhood lymphoblastic lymphoma recurrent mycosis fungoides/sezary syndrome recurrent cutaneous t-cell non-hodgkin lymphoma recurrent/refractory childhood hodgkin lymphoma relapsing chronic myelogenous leukemia acute undifferentiated leukemia