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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00003750
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : August 8, 2014
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

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.

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

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : October 2001
Actual Primary Completion Date : January 2005
Actual Study Completion Date : September 2005

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Determine the MTD and pharmacokinetics of hu14.18-IL2 fusion protein
    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 :
  1. Assess immunological changes associated with fusion protein therapy

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00003750

Show Show 59 study locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
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Study Chair: Paul M. Sondel, MD, PhD University of Wisconsin, Madison

Publications of Results:
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Responsible Party: Children's Oncology Group Identifier: NCT00003750    
Other Study ID Numbers: ADVL0018
COG-ADVL0018 ( Other Identifier: Children's Oncology Group )
CDR0000066870 ( Other Identifier: Clinical )
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: August 8, 2014
Last Verified: August 2014
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:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms, Connective and Soft Tissue
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neoplasms, Glandular and Epithelial
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents