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

This study has been completed.
Information provided by (Responsible Party):
Children's Oncology Group Identifier:
First received: November 1, 1999
Last updated: August 6, 2014
Last verified: August 2014

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.

Condition Intervention Phase
Melanoma (Skin)
Unspecified Childhood Solid Tumor, Protocol Specific
Biological: hu14.18-IL2 fusion protein
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/IB Intergroup Trial of the HU14.18-IL2 Fusion Protein in Children With Refractory Neuroblastoma and Other GD2 Positive Tumors

Resource links provided by NLM:

Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Determine the MTD and pharmacokinetics of hu14.18-IL2 fusion protein [ Designated as safety issue: No ]
    Determine the MTD of hu14.18-IL2 fusion protein and determine the pharmacokinetics of the fusion protein when given as I.V. injections

Secondary Outcome Measures:
  • Assess immunological changes associated with fusion protein therapy [ Designated as safety issue: No ]

Enrollment: 28
Study Start Date: October 2001
Study Completion Date: September 2005
Primary Completion Date: January 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DG2 positive relapsed or refractory solid tumors
The initial hu14.18-IL2 fusion protein (FP) dose will be 2 mg/m2 given intravenously over 4 hours, daily for 3 days. Five separate dose levels are scheduled: 2 mg/m²/dose (IV over 4 hours) x 3 days, 4 mg/m²/dose (IV over 4 hours) x 3 days, 6 mg/m²/dose (IV over 4 hours) x 3 days, 8 mg/m²/dose (IV over 4 hours) x 3 days, 10 mg/m²/dose (IV over 4 hours) x 3 days.
Biological: hu14.18-IL2 fusion protein

Detailed Description:


  • 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.


Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • 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



  • 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


  • 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)


  • Bilirubin less than 1.5 mg/dL
  • ALT or AST no greater than 2.5 times normal
  • Hepatitis B surface antigen negative


  • Creatinine no greater than 1.5 mg/dL OR
  • Creatinine clearance or radioisotope glomerular filtration rate at least 60 mL/min


  • 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


  • 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


  • No seizure disorders requiring antiseizure medications
  • No significant neurologic deficit or grade 2 or greater objective peripheral neuropathy


  • 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


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


  • 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


  • See Disease Characteristics
  • At least 3 weeks since prior radiotherapy
  • No concurrent palliative radiotherapy


  • See Disease Characteristics
  • At least 2 weeks since prior major surgery (e.g., laparotomy or thoracotomy)
  • No prior organ allografts
  • No concurrent palliative surgery


  • Recovered from prior therapy
  • At least 1 week since prior tretinoin
  • At least 3 weeks since prior immunosuppressive therapy
  • No other concurrent immunosuppressive drugs
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00003750

  Show 59 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Study Chair: Paul M. Sondel, MD, PhD University of Wisconsin, Madison
  More Information

Additional Information:
Responsible Party: Children's Oncology Group Identifier: NCT00003750     History of Changes
Other Study ID Numbers: ADVL0018, COG-ADVL0018, CDR0000066870
Study First Received: November 1, 1999
Last Updated: August 6, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
metastatic osteosarcoma
recurrent neuroblastoma
recurrent osteosarcoma
recurrent melanoma
unspecified childhood solid tumor, protocol specific
metastatic childhood soft tissue sarcoma
recurrent childhood soft tissue sarcoma

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Neuroendocrine Tumors
Nevi and Melanomas
Antibodies, Monoclonal
Analgesics, Non-Narcotic
Antineoplastic Agents
Central Nervous System Agents
Immunologic Factors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses processed this record on November 25, 2014