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Sponsors and Collaborators: |
Children's Oncology Group National Cancer Institute (NCI) |
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Information provided by: | National Cancer Institute (NCI) |
ClinicalTrials.gov Identifier: | NCT00005576 |
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 |
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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 |
Estimated Enrollment: | 16 |
Study Start Date: | January 2001 |
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.
Ages Eligible for Study: | up to 21 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
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
Study Chair: | Andrew L. Gilman, MD | Children's Mercy Hospital |
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 |
regional neuroblastoma disseminated neuroblastoma recurrent neuroblastoma |
Anti-HIV Agents Neuroectodermal Tumors, Primitive Immunologic Factors Antiviral Agents Neuroblastoma Recurrence Antibodies, Monoclonal Neuroectodermal Tumors Antibodies |
Aldesleukin Anti-Retroviral Agents Interleukin-2 Neoplasms, Germ Cell and Embryonal Isotretinoin Neuroepithelioma Neuroectodermal Tumors, Primitive, Peripheral Neoplasms, Glandular and Epithelial Immunoglobulins |
Anti-Infective Agents Anti-HIV Agents Neuroectodermal Tumors, Primitive Neoplasms by Histologic Type Immunologic Factors Antineoplastic Agents Physiological Effects of Drugs Neoplasms, Nerve Tissue Antiviral Agents Pharmacologic Actions Neuroblastoma Antibodies, Monoclonal |
Neuroectodermal Tumors Neoplasms Antibodies Aldesleukin Anti-Retroviral Agents Therapeutic Uses Neoplasms, Germ Cell and Embryonal Isotretinoin Neoplasms, Neuroepithelial Dermatologic Agents Neuroectodermal Tumors, Primitive, Peripheral Neoplasms, Glandular and Epithelial |