bl22 immunotoxin in treating young patients with relapsed or refractory acute lymphoblastic leukemia or non-hodgkin's lymphoma

Conditions: Leukemia; Lymphoma

Summary: rationale: bl22 immunotoxin can locate tumor cells and kill them without harming normal cells. bl22 immunotoxin may be effective in treating relapsed or refractory acute lymphoblastic leukemia and non-hodgkin's lymphoma. purpose: this phase i trial is studying the side effects and best dose of bl22 immunotoxin in treating young patients with relapsed or refractory acute lymphoblastic leukemia or non-hodgkin's lymphoma.

objectives: primary * determine the toxic effects of bl22 immunotoxin in pediatric patients with relapsed or refractory cd22-positive acute lymphoblastic leukemia or non-hodgkin's lymphoma. * determine the maximum tolerated dose of this drug in these patients. * determine the immunogenicity of this drug in these patients. * determine the pharmacokinetics of this drug in these patients. secondary * determine the in vitro cytotoxicity of this drug against lymphoblasts from patients with acute lymphoblastic leukemia. * determine the therapeutic efficacy of this drug in inducing remissions in these patients. * determine changes in lymphocyte subsets, immunoglobulin levels, serum cytokines, and soluble cytokine receptor levels in patients treated with this drug. outline: this is a non-randomized, dose-escalation study. patients receive bl22 immunotoxin iv over 30 minutes on days 1, 3, and 5 or on days 1, 3, 5, 7, 9, and 11. treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. patients who achieve a complete response (cr) or unconfirmed cr (cru) receive 2 additional courses beyond cr or cru for a maximum of 6 courses. cohorts of 3-6 patients receive escalating doses of bl22 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, the cohort is expanded and a total of 12 patients are treated at that dose. patients are followed weekly for at least 1 month and then every 1-3 months thereafter. projected accrual: a total of 95 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed acute lymphoblastic leukemia (all) or non-hodgkin's lymphoma (including lymphoblastic lymphoma, burkitt's lymphoma, and large cell lymphoma) * not amenable to available curative therapies * relapsed or refractory disease after at least 1 standard chemotherapy and 1 salvage regimen * cd22 positive according to at least 1 of the following criteria: * more than 15% cd22-positive malignant cells by immunohistochemistry * more than 30% cd22-positive malignant cells by fluorescent-activated cell sorter analysis * measurable or evaluable disease * prior cns involvement allowed provided there is no current evidence of cns malignancy * no cns leukemia or lymphoma as manifested by any of the following: * cerebrospinal fluid (csf) wbc ≥ 5/mm\^3 and confirmation of csf blasts * cranial neuropathies secondary to underlying malignancy * radiologically detected cns lymphoma * no isolated testicular all * ineligible for or refused hematopoietic stem cell transplantation or has disease activity that prohibits the time required to identify a suitable stem cell donor patient characteristics: age * 6 months to 24 years performance status * ecog 0-3 (12 to 24 years of age) * lansky 40-100% (under 12 years of age) life expectancy * not specified hematopoietic * see disease characteristics * absolute neutrophil count \> 1,000/mm\^3 \* * platelet count \> 50,000/mm\^3 \* note: \*non-leukemic patients only hepatic * bilirubin ≤ 2.0 mg/dl * ast and alt ≤ 5 times upper limit of normal * no active hepatitis b or c infection renal * creatinine normal for age or * creatinine clearance ≥ 60 ml/min immunologic * no serum neutralization of more than 75% of the activity of 1 µg/ml of study drug * hiv negative other * 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 other significant organ dysfunction that would preclude study participation * no psychiatric illness or social situation that would preclude study compliance prior concurrent therapy: biologic therapy * see disease characteristics * at least 1 week since prior colony-stimulating factors (e.g., filgrastim \[g-csf\], sargramostim \[gm-csf\], or epoetin alfa) * prior autologous or allogeneic hematopoietic stem cell transplantation (hsct) allowed * more than 100 days since prior allogeneic hsct chemotherapy * see disease characteristics * at least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas) endocrine therapy * concurrent corticosteroids allowed provided there has been no increase in the dose 1 week prior to and after study entry * steroid taper allowed radiotherapy * at least 3 weeks since prior radiotherapy * allowed in the past 3 weeks provided the volume of the bone marrow treated is \< 10% and the patients has measurable disease outside of the radiation port surgery * not specified other * recovered from prior therapy * at least 30 days since prior investigational drugs * no other concurrent investigational drugs

Keywords: recurrent childhood acute lymphoblastic leukemia burkitt lymphoma recurrent childhood large cell lymphoma recurrent childhood lymphoblastic lymphoma childhood non-hodgkin lymphoma