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A Phase I/IB Intergroup Trial of the HU14.18-IL2 Fusion Protein in Children With Refractory Neuroblastoma and Other GD2 Positive Tumors

Phase 1
21 Years
Open (Enrolling)
Melanoma (Skin), Neuroblastoma, Sarcoma, Unspecified Childhood Solid Tumor, Protocol Specific

Thank you

Trial Information

A Phase I/IB Intergroup Trial of the HU14.18-IL2 Fusion Protein in Children With Refractory Neuroblastoma and Other GD2 Positive Tumors


- 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

- Quantitate the antifusion protein antibodies in patients treated with fusion protein.

- Evaluate antitumor responses resulting from this fusion protein regimen in these

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.

Inclusion Criteria


- 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

- 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

- Histologically confirmed recurrent osteogenic sarcoma after prior chemotherapy

- 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


- 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)

- 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

- 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

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Paul M. Sondel, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Wisconsin, Madison


United States: Federal Government

Study ID:




Start Date:

May 2001

Completion Date:

Related Keywords:

  • Melanoma (Skin)
  • Neuroblastoma
  • Sarcoma
  • Unspecified Childhood Solid Tumor, Protocol Specific
  • metastatic osteosarcoma
  • recurrent neuroblastoma
  • recurrent osteosarcoma
  • recurrent melanoma
  • unspecified childhood solid tumor, protocol specific
  • metastatic childhood soft tissue sarcoma
  • recurrent childhood soft tissue sarcoma
  • Melanoma
  • Neuroblastoma
  • Sarcoma



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University of Texas - MD Anderson Cancer Center Houston, Texas  77030-4009
University of Michigan Comprehensive Cancer Center Ann Arbor, Michigan  48109-0752
Children's Hospital of Philadelphia Philadelphia, Pennsylvania  19104
Mayo Clinic Cancer Center Rochester, Minnesota  55905
Jonsson Comprehensive Cancer Center, UCLA Los Angeles, California  90095-1781
Indiana University Cancer Center Indianapolis, Indiana  46202-5265
University of Minnesota Cancer Center Minneapolis, Minnesota  55455
University of Mississippi Medical Center Jackson, Mississippi  39216-4505
Duke Comprehensive Cancer Center Durham, North Carolina  27710
Children's Hospital of Michigan Detroit, Michigan  48201
University of Texas Health Science Center at San Antonio San Antonio, Texas  78284-7811
Midwest Children's Cancer Center Milwaukee, Wisconsin  53226
NYU School of Medicine's Kaplan Comprehensive Cancer Center New York, New York  10016
Huntsman Cancer Institute Salt Lake City, Utah  84112
University of Wisconsin Comprehensive Cancer Center Madison, Wisconsin  53792
CCOP - Columbia River Oncology Program Portland, Oregon  97225
Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center Nashville, Tennessee  37232-2516
CCOP - Scott and White Hospital Temple, Texas  76508
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland  21231-2410
University of Arkansas for Medical Sciences Little Rock, Arkansas  72205
MBCCOP - LSU Health Sciences Center New Orleans, Louisiana  70112
Children's Hospital Los Angeles Los Angeles, California  90027-0700
Children's Hospital of Orange County Orange, California  92668
Children's National Medical Center Washington, District of Columbia  20010-2970
Children's Mercy Hospital Kansas City, Missouri  64108
Children's Hospital of Columbus Columbus, Ohio  43205-2696
Children's Hospital of Pittsburgh Pittsburgh, Pennsylvania  15213
Children's Hospital and Regional Medical Center - Seattle Seattle, Washington  98105
Rebecca and John Moores UCSD Cancer Center La Jolla, California  92093-0658
Children's Memorial Hospital - Chicago Chicago, Illinois  60614
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute Boston, Massachusetts  02115
Floating Hospital for Children Boston, Massachusetts  02111
Cardinal Glennon Children's Hospital Saint Louis, Missouri  63104
Washington University Medical Center Saint Louis, Missouri  63105
St. Jude Children's Research Hospital Memphis, Tennessee  38105-2794
Cook Children's Medical Center - Fort Worth Fort Worth, Texas  76104
Texas Children's Cancer Center Houston, Texas  77030-2399
City of Hope Comprehensive Cancer Center Duarte, California  91010
UCSF Comprehensive Cancer Center San Francisco, California  94115
Herbert Irving Comprehensive Cancer Center at Columbia University New York, New York  10032
Stanford Cancer Center at Stanford University Medical Center Stanford, California  94305
Arkansas Children's Hospital Little Rock, Arkansas  72202-3591
Cincinnati Children's Hospital Medical Center Cincinnati, Ohio  45229-3039
Hollings Cancer Center at Medical University of South Carolina Charleston, South Carolina  29425
CCOP - Marshfield Clinic Research Foundation Marshfield, Wisconsin  54449
Robert Wood Johnson Medical School New Brunswick, New Jersey  08903
Shands Cancer Center at the University of Florida Health Science Center Gainesville, Florida  32610-0296
Cancer Center at Hackensack University Medical Center Hackensack, New Jersey  07601
University Hospital at State University of New York - Upstate Medical University Syracuse, New York  13210
Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas Dallas, Texas  75390-9063
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish RiteCampus Atlanta, Georgia  30342
Kansas Cancer Institute at the University of Kansas Medical Center Kansas City, Kansas  66160-7357
Oklahoma University Medical Center at University of Oklahoma Health Sciences Center Oklahoma City, Oklahoma  73126