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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.
First Received: November 1, 1999   Last Updated: February 6, 2009   History of Changes
Sponsor: Children's Oncology Group
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00003750
  Purpose

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.


Condition Intervention Phase
Melanoma (Skin)
Neuroblastoma
Sarcoma
Unspecified Childhood Solid Tumor, Protocol Specific
Biological: hu14.18-IL2 fusion protein
Phase I

Study Type: Interventional
Study Design: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment: 24
Study Start Date: May 2001
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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_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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00003750

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

Additional Information:
Publications:
Study ID Numbers: CDR0000066870, COG-ADVL0018
Study First Received: November 1, 1999
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00003750     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
metastatic osteosarcoma
recurrent neuroblastoma
recurrent osteosarcoma
recurrent melanoma
unspecified childhood solid tumor, protocol specific
metastatic childhood soft tissue sarcoma
recurrent childhood soft tissue sarcoma

Additional relevant MeSH terms:
Neuroectodermal Tumors, Primitive
Immunologic Factors
Antineoplastic Agents
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Neuroblastoma
Melanoma
Antibodies, Monoclonal
Neoplasms, Connective and Soft Tissue
Sensory System Agents
Neoplasms, Germ Cell and Embryonal
Therapeutic Uses
Nevi and Melanomas
Analgesics
Neoplasms by Histologic Type
Pharmacologic Actions
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms
Interleukin-2
Analgesics, Non-Narcotic
Sarcoma
Peripheral Nervous System Agents
Neoplasms, Neuroepithelial
Central Nervous System Agents
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 27, 2009