Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	21 and under	NCI	COG-ADVL0018 NCT00003750

Objectives

1. Determine the maximum tolerated dose of hu14.18-interleukin-2 fusion protein in children with refractory or recurrent neuroblastoma or other GD2-positive tumors.
2. Determine the toxicity and pharmacokinetics of the fusion protein in these patients.
3. Determine the effect of the fusion protein on systemic immune modulation in these patients.
4. Quantitate the antifusion protein antibodies in patients treated with fusion protein.
5. Evaluate antitumor responses resulting from this fusion protein regimen in these patients.

Entry 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

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

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/mm³
• Platelet count at least 75,000/mm³ (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:

• FEV₁ 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

Expected Enrollment

A total of 18-24 patients will be accrued for this study within 1 year.

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.

Osenga KL, Hank JA, Albertini MR, et al.: A phase I clinical trial of the hu14.18-IL2 (EMD 273063) as a treatment for children with refractory or recurrent neuroblastoma and melanoma: a study of the Children's Oncology Group. Clin Cancer Res 12 (6): 1750-9, 2006.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Paul Sondel, MD, PhD, Protocol chair		Ph: 608-263-9069; 800-622-8922 Email: pmsondel@facstaff.wisc.edu

Registry Information
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
Trial Start Date		2001-05-04
Registered in ClinicalTrials.gov		NCT00003750
Date Submitted to PDQ		1999-01-13
Information Last Verified		2004-04-27
NCI Grant/Contract Number		CA57746

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