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.
Study Type
INTERVENTIONAL
Purpose
TREATMENT
Enrollment
40
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States
Doernbecher Children's Hospital at Oregon Health & Science University
Portland, Oregon, United States
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St. Jude Children's Research Hospital
Memphis, Tennessee, United States