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 recurrentneuroblastoma or other tumors.

Condition	Treatment or Intervention	Phase
childhood soft tissue sarcoma childhood solid tumor Melanoma Neuroblastoma Osteosarcoma	Drug: hu14.18-interleukin-2 fusion protein  Procedure: biological response modifier therapy  Procedure: targeted fusion protein therapy	Phase I

Further Study Details: 

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.

Ages Eligible for Study:  up to  21 Years,  Genders Eligible for Study:  Both

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
• 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

Arkansas
      Arkansas Children's Hospital, Little Rock,  Arkansas,  72202-3591,  United States
      University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States
California
      Children's Hospital Los Angeles, Los Angeles,  California,  90027-0700,  United States
      Children's Hospital of Orange County, Orange,  California,  92868,  United States
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States
      Rebecca and John Moores UCSD Cancer Center, La Jolla,  California,  92093-0658,  United States
      Stanford Cancer Center at Stanford University Medical Center, Stanford,  California,  94305-5208,  United States
      UCSF Comprehensive Cancer Center, San Francisco,  California,  94115,  United States
District of Columbia
      Children's National Medical Center, Washington,  District of Columbia,  20010-2970,  United States
Florida
      Shands Cancer Center at the University of Florida Health Science Center, Gainesville,  Florida,  32610-0296,  United States
Georgia
      AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish RiteCampus, Atlanta,  Georgia,  30342,  United States
Illinois
      Children's Memorial Hospital - Chicago, Chicago,  Illinois,  60614,  United States
Indiana
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5289,  United States
Kansas
      Kansas Cancer Institute at the University of Kansas Medical Center, Kansas City,  Kansas,  66160-7357,  United States
Louisiana
      MBCCOP - LSU Health Sciences Center, New Orleans,  Louisiana,  70112,  United States
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231-2410,  United States
Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States
      Floating Hospital for Children, Boston,  Massachusetts,  02111,  United States
Michigan
      Children's Hospital of Michigan, Detroit,  Michigan,  48201,  United States
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0914,  United States
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States
Mississippi
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States
Missouri
      Cardinal Glennon Children's Hospital, Saint Louis,  Missouri,  63104,  United States
      Children's Mercy Hospital, Kansas City,  Missouri,  64108,  United States
      Washington University Medical Center, Saint Louis,  Missouri,  63105,  United States
New Jersey
      Cancer Center at Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States
      Robert Wood Johnson Medical School, New Brunswick,  New Jersey,  08901,  United States
New York
      Herbert Irving Comprehensive Cancer Center at Columbia University, New York,  New York,  10032,  United States
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States
      NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York,  New York,  10016,  United States
      University Hospital at State University of New York - Upstate Medical University, Syracuse,  New York,  13210,  United States
North Carolina
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States
Ohio
      Children's Hospital of Columbus, Columbus,  Ohio,  43205-2696,  United States
      Cincinnati Children's Hospital Medical Center, Cincinnati,  Ohio,  45229-3039,  United States
Oklahoma
      Oklahoma University Medical Center at University of Oklahoma Health Sciences Center, Oklahoma City,  Oklahoma,  73126,  United States
Oregon
      CCOP - Columbia River Oncology Program, Portland,  Oregon,  97225,  United States
Pennsylvania
      Children's Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States
      Children's Hospital of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States
South Carolina
      Hollings Cancer Center at Medical University of South Carolina, Charleston,  South Carolina,  29425-0721,  United States
Tennessee
      St. Jude Children's Research Hospital, Memphis,  Tennessee,  38105-2794,  United States
      Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center, Nashville,  Tennessee,  37232-6838,  United States
Texas
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States
      Cook Children's Medical Center - Fort Worth, Fort Worth,  Texas,  76104,  United States
      Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas,  Texas,  75390-9063,  United States
      Texas Children's Cancer Center, Houston,  Texas,  77030-2399,  United States
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030-4009,  United States
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78207,  United States
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84112,  United States
Washington
      Children's Hospital and Regional Medical Center - Seattle, Seattle,  Washington,  98105,  United States
Wisconsin
      CCOP - Marshfield Clinic Research Foundation, Marshfield,  Wisconsin,  54449,  United States
      Midwest Children's Cancer Center, Milwaukee,  Wisconsin,  53226,  United States
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-6164,  United States
Australia, Victoria
      Royal Children's Hospital, Parkville,  Victoria,  3052,  Australia
Australia, Western Australia
      Princess Margaret Hospital for Children, Perth,  Western Australia,  6001,  Australia
Canada, Ontario
      Hospital for Sick Children, Toronto,  Ontario,  M5G 1X8,  Canada
Canada, Quebec
      Hopital Sainte Justine, Montreal,  Quebec,  H3T 1C5,  Canada
      McGill University Health Center - Montreal Children's Hospital, Montreal,  Quebec,  H3G 1A4,  Canada

Study chairs or principal investigators

Paul M. Sondel, MD, PhD,  Study Chair,  University of Wisconsin Comprehensive Cancer Center   

Study ID Numbers:  CDR0000066870; COG-ADVL0018
Record last reviewed:  June 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003750
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08