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Biological Therapy in Treating Children With Refractory or Recurrent Neuroblastoma or Other Tumors

A Phase I/IB Intergroup Trial of the HU14.18-IL2 Fusion Protein in Children With Refractory Neuroblastoma and Other GD2 Positive Tumors

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00003750
Enrollment
28
Registered
2003-01-27
Start date
2001-10-31
Completion date
2005-09-30
Last updated
2014-08-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Melanoma (Skin), Neuroblastoma, Sarcoma, Unspecified Childhood Solid Tumor, Protocol Specific

Keywords

metastatic osteosarcoma, recurrent neuroblastoma, recurrent osteosarcoma, recurrent melanoma, unspecified childhood solid tumor, protocol specific, metastatic childhood soft tissue sarcoma, recurrent childhood soft tissue sarcoma

Brief summary

RATIONALE: Biological therapies such as hu14.18-interleukin-2 fusion protein use different ways to stimulate the immune system and stop cancer cells from growing. PURPOSE: Phase I trial to study the effectiveness of hu14.18-interleukin-2 fusion protein in treating children who have refractory or recurrent neuroblastoma or other tumors.

Detailed description

OBJECTIVES: * Determine the maximum tolerated dose of hu14.18-interleukin-2 fusion protein in children with refractory or recurrent neuroblastoma or other GD2-positive tumors. * Determine the toxicity and pharmacokinetics of the fusion protein in these patients. * Determine the effect of the fusion protein on systemic immune modulation in these patients. * Quantitate the antifusion protein antibodies in patients treated with fusion protein. * Evaluate antitumor responses resulting from this fusion protein regimen in these patients. OUTLINE: This is a dose-escalation study. Patients receive hu14.18-interleukin-2 (hu14.18-IL2) fusion protein IV over 4 hours once daily on days 1-3. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of hu14.18-IL2 fusion protein until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients are followed every 2 months for 1 year, every 6 months for 3 years, and then annually for 5 years. PROJECTED ACCRUAL: A total of 18-24 patients will be accrued for this study within 1 year.

Interventions

Sponsors

National Cancer Institute (NCI)
CollaboratorNIH
Children's Oncology Group
Lead SponsorNETWORK

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
No minimum to 21 Years
Healthy volunteers
No

Inclusion criteria

DISEASE CHARACTERISTICS: * Histologically confirmed neuroblastoma or melanoma at original diagnosis * Refractory to chemotherapy or recurrence after prior multiagent chemotherapy * Measurable or evaluable (detectable by bone scan) metastatic disease OR * No evidence of disease if complete response to prior surgical resection, radiotherapy, and/or chemotherapy OR * Histologically confirmed tumor expressing GD2 antigen at original diagnosis or relapse * Refractory to standard treatment * Measurable or evaluable disease by clinical assessments or laboratory markers OR * No evidence of disease after prior surgical resection of metastatic, recurrent disease * Histologically confirmed recurrent osteogenic sarcoma after prior chemotherapy allowed * Soft tissue sarcoma allowed * No primary CNS tumors * Prior CNS metastases allowed, provided: * Disease previously treated * Disease clinically stable for 4 weeks before study * At least 4 weeks since prior steroids for CNS metastases * No clinically detectable pleural effusions or ascites PATIENT CHARACTERISTICS: Age: * 21 and under Performance status: * Karnofsky 60-100% for children over age 10 * Lansky 60-100% for children age 10 and under Life expectancy: * At least 12 weeks Hematopoietic: * Absolute neutrophil count greater than 1,000/mm\^3 * Platelet count at least 75,000/mm\^3 (transfusion allowed) * Hemoglobin at least 9.0 g/dL (transfusion allowed) Hepatic: * Bilirubin less than 1.5 mg/dL * ALT or AST no greater than 2.5 times normal * Hepatitis B surface antigen negative Renal: * Creatinine no greater than 1.5 mg/dL OR * Creatinine clearance or radioisotope glomerular filtration rate at least 60 mL/min Cardiovascular: * Shortening fraction at least 27% by echocardiogram OR * Ejection fraction more than 50% by MUGA scan * No congestive heart failure * No uncontrolled cardiac rhythm disturbance Pulmonary: * FEV\_1 and FVC more than 60% of predicted OR * No dyspnea at rest * No exercise intolerance * Oxygen saturation more than 94% by pulse oximetry on room air Neurologic: * No seizure disorders requiring antiseizure medications * No significant neurologic deficit or grade 2 or greater objective peripheral neuropathy Other: * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * HIV negative * No significant concurrent illnesses unrelated to cancer or its treatment * No significant psychiatric disabilities * No uncontrolled active infections * No uncontrolled active peptic ulcer PRIOR CONCURRENT THERAPY: Biologic therapy: * At least 1 week since prior growth factors * At least 1 week since prior immunomodulatory therapy * Prior monoclonal antibodies allowed if no detectable antibody to hu14.18 * Prior autologous bone marrow transplantation (BMT) or stem cell transplantation (SCT) allowed * Prior autologous BMT or SCT with monoclonal antibody-purged specimens allowed * No concurrent growth factors * No concurrent interferon Chemotherapy: * See Disease Characteristics * At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas, mitomycin, or melphalan) * No concurrent palliative chemotherapy Endocrine therapy: * See Disease Characteristics * At least 2 weeks since prior glucocorticoids, except for life-threatening symptoms * No concurrent corticosteroids * No concurrent glucocorticoids, except for life-threatening symptoms Radiotherapy: * See Disease Characteristics * At least 3 weeks since prior radiotherapy * No concurrent palliative radiotherapy Surgery: * See Disease Characteristics * At least 2 weeks since prior major surgery (e.g., laparotomy or thoracotomy) * No prior organ allografts * No concurrent palliative surgery Other: * Recovered from prior therapy * At least 1 week since prior tretinoin * At least 3 weeks since prior immunosuppressive therapy * No other concurrent immunosuppressive drugs

Design outcomes

Primary

MeasureTime frameDescription
Determine the MTD and pharmacokinetics of hu14.18-IL2 fusion proteinDetermine the MTD of hu14.18-IL2 fusion protein and determine the pharmacokinetics of the fusion protein when given as I.V. injections

Secondary

MeasureTime frame
Assess immunological changes associated with fusion protein therapy

Countries

Australia, Canada, United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026