Monoclonal Antibody Therapy With Sargramostim and Interleukin-2 in Treating Children With Neuroblastoma

Condition(s) targeted: Neuroblastoma

Intervention: aldesleukin (Drug); isotretinoin (Drug); monoclonal antibody Ch14.18 (Drug); sargramostim (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Children's Oncology Group

Official(s) and/or principal investigator(s):
Andrew L. Gilman, MD, Study Chair, Affiliation: Children's Mercy Hospital

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.

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

Study design: Treatment

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.

Minimum age: N/A. Maximum age: 21 Years. Gender(s): Both.

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

University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, United States

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

Children's National Medical Center, Washington, District of Columbia 20010-2970, United States

Emory University Hospital - Atlanta, Atlanta, Georgia 30322, United States

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 University Cancer Center, Indianapolis, Indiana 46202-5289, United States

University of Kansas Medical Center, Kansas City, Kansas 66160-7357, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231-2410, United States

Boston Floating Hospital Infants and Children, Boston, Massachusetts 02111, United States

Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States

Children's Hospital of Michigan, Detroit, Michigan 48201, United States

University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109-0752, United States

Mayo Clinic Cancer Center, Rochester, Minnesota 55905, United States

University of Minnesota Cancer Center, Minneapolis, Minnesota 55455, United States

University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, United States

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

Cancer Institute of New Jersey, New Brunswick, New Jersey 08901, United States

Hackensack University Medical Center, Hackensack, New Jersey 07601, United States

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

Duke Comprehensive Cancer Center, Durham, North Carolina 27710, United States

Children's Hospital Medical Center - Cincinnati, Cincinnati, Ohio 45229-3039, United States

Children's Hospital of Columbus, Columbus, Ohio 43205-2696, United States

University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190, United States

Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States

Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States

Hopital Sainte Justine, Montreal, Quebec H3T 1C5, Canada

McGill University Health Center - Montreal Children's Hospital, Montreal, Quebec H3H 1P3, Canada

Medical University of South Carolina, Charleston, South Carolina 29425-0721, United States

Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232-6838, United States

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

Primary Children's Medical Center, Salt Lake City, Utah 84113, United States

Royal Children's Hospital, Parkville, Victoria 3052, Australia

Children's Hospital and Regional Medical Center - Seattle, Seattle, Washington 98105, United States

Princess Margaret Hospital for Children, Perth, Western Australia 6001, Australia

Midwest Children's Cancer Center, Milwaukee, Wisconsin 53226, United States

University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin 53792-6164, United States

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: January 2001
Last updated: May 23, 2008