Phase I trial to compare the effectiveness of interleukin-12 with or without interleukin-2 in treating young patients who have refractory or recurrent neuroblastoma. Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Combining interleukin-2 with interleukin-12 may kill more tumor cells.
OBJECTIVES: I. Define the maximum tolerated dose and dose-limiting toxicity of interleukin-12 with or without interleukin-2 in patients with refractory or recurrent neuroblastoma. II. Determine, preliminarily, the antitumor effect of interleukin-12 with or without interleukin-2 in these patients. III. Evaluate the immunoregulatory activity of interleukin-12 with or without interleukin-2 in these patients. IV. Evaluate the antiangiogenic activity of interleukin-12 with or without interleukin-2 in these patients. OUTLINE: This is a dose-escalation, multicenter study. Patients are assigned to 1 of 2 treatment cohorts. COHORT A: Patients receive interleukin-12 (IL-12) IV over 5-15 seconds on days 1, 3, 5, 8, 10, and 12. COHORT B: Patients receive interleukin-2 (IL-2) IV over 15 minutes twice daily on days 1 and 8 and IL-12 IV as in cohort A. Treatment in both cohorts repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Some patients may receive additional courses at the discretion of the principal investigator. Cohorts of 3-6 patients in both cohorts receive escalating doses of IL-2 and IL-12 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, an additional cohort of 8 patients receives IL-12 and IL-2 at the MTD. Patients are followed at 3 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Given IV
Given IV
New Approaches to Neuroblastoma Treatment (NANT)
Los Angeles, California, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Maximum tolerated dose (MTD) assessed by Common Toxicity Criteria (CTC)
Time frame: 28 days
Overall response assessed by Response Evaluation Criteria for Solid Tumors (RECIST)
Time frame: Up to 3 weeks
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Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States
University of California at San Francisco - Comprehensive Cancer Center
San Francisco, California, United States
AFLAC Cancer Center and Blood Disorders Service
Atlanta, Georgia, United States
Childrens Memorial Hospital
Chicago, Illinois, United States
Riley Hospital for Children
Indianapolis, Indiana, United States
Children's Hospital Boston
Boston, Massachusetts, United States
University of Michigan University Hospital
Ann Arbor, Michigan, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
...and 4 more locations