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Monoclonal Antibody Therapy With Sargramostim and Interleukin-2 in Treating Children With Neuroblastoma
This study has been completed.
First Received: May 2, 2000   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: NCT00005576
  Purpose

RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood. Interleukin-2 may stimulate a person's white blood cells to kill cancer cells. Combining monoclonal antibody therapy with sargramostim or interleukin-2 may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of monoclonal antibody therapy given with sargramostim and interleukin-2 in treating children with neuroblastoma who have just completed bone marrow or peripheral stem cell transplantation.


Condition Intervention Phase
Neuroblastoma
Biological: aldesleukin
Biological: monoclonal antibody Ch14.18
Biological: sargramostim
Drug: isotretinoin
Phase I

Study Type: Interventional
Study Design: Treatment
Official Title: A PHASE I STUDY OF CHIMERIC HUMAN/MURINE ANTI-GD2 MONOCLONAL ANTIBODY (ch14.18) WITH GM-CSF IN CHILDREN WITH NEUROBLASTOMA AND OTHER GD2 POSITIVE MALIGNANCIES IMMEDIATELY POST AUTOLOGOUS BMT

Resource links provided by NLM:


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

Estimated Enrollment: 16
Study Start Date: January 2001
Detailed Description:

OBJECTIVES: I. Determine the maximum tolerated dose of monoclonal antibody (MOAB) Ch14.18 when combined with sargramostim (GM-CSF) and interleukin-2 (IL-2) after autologous bone marrow or peripheral blood stem cell rescue in children with neuroblastoma. II. Determine the toxic effects of this regimen in these patients. III. Determine the pharmacokinetics, including antibody level, antibody-binding activity, and presence of human anti-chimeric antibodies, of this regimen in these patients. IV. Determine the activity of IL-2 and MOAB Ch14.18 against tumor cells in terms of response using standard clinical measurements such as bone marrow immunocytology in these patients. V. Determine the extent of coating of tumor cells (bone marrow metastases) by MOAB Ch14.18 in these patients. VI. Determine the feasibility of isotretinoin administered between courses beginning after course 2 in these patients.

OUTLINE: This is a multicenter, dose-escalation study of monoclonal antibody (MOAB) Ch14.18. Patients receive MOAB Ch14.18 IV over 5 hours on days 7-10 during courses 2 and 4 and on days 3-6 during courses 1, 3, and 5; sargramostim (GM-CSF) IV over 2 hours or subcutaneously daily on days 0-13 during courses 1, 3, and 5; interleukin-2 IV continuously on days 0-3 and 7-10 during courses 2 and 4; and oral isotretinoin twice daily on days 14-27 during courses 2 and 4 and on days 10-23 during courses 3 and 5. Treatment repeats every 24-32 days for 5 courses in the absence of unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of MOAB Ch14.18 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A minimum of 6 additional patients are treated at the MTD. Patients are followed every other week for 2 months and then every 3 months for 6 months.

PROJECTED ACCRUAL: Approximately 6-16 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: Diagnosis of neuroblastoma based on tumor histology or bone marrow metastasis with elevated urine catecholamine metabolites Confirmation of GD2-positivity not required Must have recently completed a course of myeloablative therapy followed by autologous bone marrow or peripheral blood stem cell (PBSC) rescue May be eligible: After completion of the third course of high-dose chemotherapy with PBSC rescue on protocol CCG-3951 After completion of 1 or more courses of high-dose chemotherapy with PBSC rescue on an institutional (local) protocol Previous treatment on phase I studies (e.g., CCG-3951) allowed Ineligible if evaluable for response on a Phase II/III protocol (e.g., CCG-6921, CCG-3891) Patients who are no longer evaluable for response on a Phase II/III protocol (i.e., disease progression after therapy) are allowed

PATIENT CHARACTERISTICS: Age: 21 and under Performance status: 0-2 Life expectancy: At least 2 months Hematopoietic: Absolute phagocyte count (neutrophils and monocytes) greater than 1,000/mm3 Hepatic: Bilirubin no greater than 1.5 times normal SGOT or SGPT no greater than 5.0 times normal Concurrent veno-occlusive disease allowed if stable or improving Renal: Creatinine no greater than 1.5 times normal OR Creatinine clearance or radioisotope glomerular filtration rate at least 60 mL/min Cardiovascular: Shortening fraction at least 27% by echocardiogram OR Ejection fraction greater than 50% by MUGA scan Pulmonary: FEV1 and FVC greater than 60% predicted OR For children who cannot perform pulmonary function tests: No evidence of dyspnea at rest No exercise intolerance Oxygen saturation greater than 94% on room air by pulse oximetry Other: No CNS toxicity greater than grade 1 Concurrent seizure disorder allowed if on anticonvulsants and well controlled

PRIOR CONCURRENT THERAPY: Biologic Therapy: See Disease Characteristics No prior monoclonal antibody (MOAB) 14G2A or MOAB Ch14.18 No other concurrent cytokines or growth factors (e.g., interferon or filgrastim (G-CSF)) Chemotherapy: See Disease Characteristics At least 2 weeks since prior myelosuppressive chemotherapy No other concurrent anticancer chemotherapy Endocrine therapy: At least 2 weeks since prior corticosteroids No concurrent corticosteroids Radiotherapy: At least 7 days since prior radiotherapy No concurrent radiotherapy except for localized painful lesions Surgery: Not specified Other: At least 2 weeks since prior immunosuppressive drugs At least 2 weeks since prior tretinoin No concurrent immunosuppressive drugs (e.g., cyclosporine) No concurrent pentoxifylline

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005576

  Hide Study Locations
Locations
United States, Arkansas
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
Children's Hospital of Orange County
Orange, California, United States, 92868
Stanford University Medical Center
Stanford, California, United States, 94305-5408
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, California, United States, 90095-1781
City of Hope National Medical Center
Duarte, California, United States, 91010
UCSF Cancer Center and Cancer Research Institute
San Francisco, California, United States, 94143-0128
University of California San Diego Cancer Center
La Jolla, California, United States, 92093-0658
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Georgia
Emory University Hospital - Atlanta
Atlanta, Georgia, United States, 30322
United States, Illinois
Children's Memorial Hospital, Chicago
Chicago, Illinois, United States, 60614
Robert H. Lurie Comprehensive Cancer Center, Northwestern University
Chicago, Illinois, United States, 60611-3013
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202-5289
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160-7357
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Massachusetts
Boston Floating Hospital Infants and Children
Boston, Massachusetts, United States, 02111
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
Children's Hospital of Michigan
Detroit, Michigan, United States, 48201
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0752
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 School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New Jersey
Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08901
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Columbia Presbyterian Hospital
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
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
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 Medical Center - Cincinnati
Cincinnati, Ohio, United States, 45229-3039
Children's Hospital of Columbus
Columbus, Ohio, United States, 43205-2696
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73190
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
Medical University of South Carolina
Charleston, South Carolina, United States, 29425-0721
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838
United States, Texas
Cook Children's Medical Center - Fort Worth
Fort Worth, Texas, United States, 76104
Simmons Cancer Center - Dallas
Dallas, Texas, United States, 75235-9154
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, 78284-7811
United States, Utah
Primary Children's Medical Center
Salt Lake City, Utah, United States, 84113
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
United States, Wisconsin
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, H3H 1P3
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Andrew L. Gilman, MD Children's Mercy Hospital
  More Information

Additional Information:
Publications:
Study ID Numbers: CDR0000063533, COG-A0935A, CCG-0935, CCG-0935A
Study First Received: May 2, 2000
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00005576     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
regional neuroblastoma
disseminated neuroblastoma
recurrent neuroblastoma

Additional relevant MeSH terms:
Anti-Infective Agents
Neuroectodermal Tumors, Primitive
Immunologic Factors
Antineoplastic Agents
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Neuroblastoma
Antibodies, Monoclonal
Anti-Retroviral Agents
Neoplasms, Germ Cell and Embryonal
Therapeutic Uses
Isotretinoin
Dermatologic Agents
Immunoglobulins
Neoplasms by Histologic Type
Anti-HIV Agents
Antiviral Agents
Pharmacologic Actions
Neuroectodermal Tumors
Antibodies
Neoplasms
Aldesleukin
Neoplasms, Neuroepithelial
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 25, 2009