Pediatric Phase I Trial of LMB-2 for Refractory CD25-Positive Leukemias and Lymphomas
- 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.
- 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
Primary Purpose: Treatment
Alan S. Wayne, MD
National Cancer Institute (NCI)
United States: Food and Drug Administration
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|
|St. Jude Children's Research Hospital||Memphis, Tennessee 38105-2794|
|Winship Cancer Institute of Emory University||Atlanta, Georgia 30322|
|Doernbecher Children's Hospital at Oregon Health & Science University||Portland, Oregon 97239-3098|
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office||Bethesda, Maryland 20892-1182|