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Biological Therapy in Treating Children With Refractory or Recurrent Neuroblastoma or Other Tumors
This study is ongoing, but not recruiting participants.
Study NCT00003750   Information provided by National Cancer Institute (NCI)
First Received: November 1, 1999   Last Updated: February 6, 2009   History of Changes

November 1, 1999
February 6, 2009
May 2001
 
 
 
Complete list of historical versions of study NCT00003750 on ClinicalTrials.gov Archive Site
 
 
 
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

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.

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.

Phase I
Interventional
Treatment
  • Melanoma (Skin)
  • Neuroblastoma
  • Sarcoma
  • Unspecified Childhood Solid Tumor, Protocol Specific
Biological: hu14.18-IL2 fusion protein
 
Osenga KL, Hank JA, Albertini MR, Gan J, Sternberg AG, Eickhoff J, Seeger RC, Matthay KK, Reynolds CP, Twist C, Krailo M, Adamson PC, Reisfeld RA, Gillies SD, Sondel PM; Children's Oncology Group. 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. 2006 Mar 15;12(6):1750-9.

*   Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
 
Active, not recruiting
24
 
 

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
Both
up to 21 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada
 
NCT00003750
 
CDR0000066870, COG-ADVL0018
Children's Oncology Group
National Cancer Institute (NCI)
Study Chair: Paul M. Sondel, MD, PhD University of Wisconsin, Madison
National Cancer Institute (NCI)
April 2004

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP