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	Treatment or Intervention	Phase
disseminated neuroblastoma regional neuroblastoma recurrent neuroblastoma	Procedure: chemotherapy  Procedure: biological response modifier therapy  Procedure: monoclonal antibody therapy  Procedure: colony-stimulating factor therapy  Procedure: antibody therapy  Procedure: cytokine therapy  Procedure: interleukin therapy  Drug: interleukin-2  Drug: interleukin-2/monoclonal antibody Ch14.18  Drug: isotretinoin  Drug: monoclonal antibody Ch14.18  Drug: monoclonal antibody Ch14.18/sargramostim  Drug: sargramostim	Phase I

Further Study Details: 

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.

PROTOCOL 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.

Ages Eligible for Study:  up to  21 Years

Criteria

PROTOCOL ENTRY 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

--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
• her: 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

--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

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

Study chairs or principal investigators

Andrew L. Gilman,  Study Chair,  Children's Oncology Group   

Study ID Numbers:  CDR0000063533; COG-A0935A; CCG-0935; CCG-0935A
Record last reviewed:  November 2003
Last Updated:  October 13, 2004
Record first received:  May 2, 2000
ClinicalTrials.gov Identifier:  NCT00005576
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08