Know Cancer

forgot password

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



Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
University of Texas - MD Anderson Cancer CenterHouston, Texas  77030-4009
University of Michigan Comprehensive Cancer CenterAnn Arbor, Michigan  48109-0752
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
Mayo Clinic Cancer CenterRochester, Minnesota  55905
Jonsson Comprehensive Cancer Center, UCLALos Angeles, California  90095-1781
Indiana University Cancer CenterIndianapolis, Indiana  46202-5265
University of Minnesota Cancer CenterMinneapolis, Minnesota  55455
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
Duke Comprehensive Cancer CenterDurham, North Carolina  27710
Children's Hospital of MichiganDetroit, Michigan  48201
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
Midwest Children's Cancer CenterMilwaukee, Wisconsin  53226
NYU School of Medicine's Kaplan Comprehensive Cancer CenterNew York, New York  10016
Huntsman Cancer InstituteSalt Lake City, Utah  84112
University of Wisconsin Comprehensive Cancer CenterMadison, Wisconsin  53792
CCOP - Columbia River Oncology ProgramPortland, Oregon  97225
Vanderbilt-Ingram Cancer Center at Vanderbilt Medical CenterNashville, Tennessee  37232-2516
CCOP - Scott and White HospitalTemple, Texas  76508
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410
University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
MBCCOP - LSU Health Sciences CenterNew Orleans, Louisiana  70112
Children's Hospital Los AngelesLos Angeles, California  90027-0700
Children's Hospital of Orange CountyOrange, California  92668
Children's National Medical CenterWashington, District of Columbia  20010-2970
Children's Mercy HospitalKansas City, Missouri  64108
Children's Hospital of ColumbusColumbus, Ohio  43205-2696
Children's Hospital of PittsburghPittsburgh, Pennsylvania  15213
Children's Hospital and Regional Medical Center - SeattleSeattle, Washington  98105
Rebecca and John Moores UCSD Cancer CenterLa Jolla, California  92093-0658
Children's Memorial Hospital - ChicagoChicago, Illinois  60614
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer InstituteBoston, Massachusetts  02115
Floating Hospital for ChildrenBoston, Massachusetts  02111
Cardinal Glennon Children's HospitalSaint Louis, Missouri  63104
Washington University Medical CenterSaint Louis, Missouri  63105
St. Jude Children's Research HospitalMemphis, Tennessee  38105-2794
Cook Children's Medical Center - Fort WorthFort Worth, Texas  76104
Texas Children's Cancer CenterHouston, Texas  77030-2399
City of Hope Comprehensive Cancer CenterDuarte, California  91010
UCSF Comprehensive Cancer CenterSan Francisco, California  94115
Herbert Irving Comprehensive Cancer Center at Columbia UniversityNew York, New York  10032
Stanford Cancer Center at Stanford University Medical CenterStanford, California  94305
Arkansas Children's HospitalLittle Rock, Arkansas  72202-3591
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Hollings Cancer Center at Medical University of South CarolinaCharleston, South Carolina  29425
CCOP - Marshfield Clinic Research FoundationMarshfield, Wisconsin  54449
Robert Wood Johnson Medical SchoolNew Brunswick, New Jersey  08903
Shands Cancer Center at the University of Florida Health Science CenterGainesville, Florida  32610-0296
Cancer Center at Hackensack University Medical CenterHackensack, New Jersey  07601
University Hospital at State University of New York - Upstate Medical UniversitySyracuse, New York  13210
Simmons Cancer Center at University of Texas Southwestern Medical Center - DallasDallas, Texas  75390-9063
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish RiteCampusAtlanta, Georgia  30342
Kansas Cancer Institute at the University of Kansas Medical CenterKansas City, Kansas  66160-7357
Oklahoma University Medical Center at University of Oklahoma Health Sciences CenterOklahoma City, Oklahoma  73126