Monoclonal Antibody Ch14.18, Sargramostim, Aldesleukin, and Isotretinoin After Autologous Stem Cell Transplant in Treating Patients With Neuroblastoma
Localized Resectable Neuroblastoma
Localized Unresectable Neuroblastoma
Stage 4S Neuroblastoma
Biological: monoclonal antibody Ch14.18
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Comprehensive Safety Trial of Chimeric Antibody 14.18 (Ch14.18) With GM-CSF, IL-2 and Isotretinoin in High-Risk Neuroblastoma Patients Following Myeloablative Therapy|
- Percentage of Patients Who Experienced a Significant (CTC Grade 3-5) Nonhematologic Toxicity of Interest (Pain, Hypotension, Allergic Reactions, Capillary Leak Syndrome, or Fever). [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]Designed to collect comprehensive safety/toxicity data, as well as additional efficacy data for the immunotherapy. To address the primary objective, descriptive analyses summarizing the number and type of AEs will be performed. The percentage of patients reporting each unacceptable (Grade 3 or higher) CTC toxicity code, tabulated by course, are reported.
- Event-free Survival [ Time Frame: From enrollment until the first occurrence of relapse, progressive disease, secondary malignancy, or death, or until last contact if no event occurred, up to 5 years ] [ Designated as safety issue: No ]Estimated using Kaplan-Meier curves.
- Overall Survival [ Time Frame: From enrollment until death, or until last contact with the patient, up to 5 years ] [ Designated as safety issue: No ]Estimated using Kaplan-Meier curves.
|Study Start Date:||December 2009|
|Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Experimental: Chimeric Antibody 14.18 with GM-CSF, IL-2 and Isotretinoin
Patients receive sargramostim subcutaneously or IV over 2 hours on days 0-13 of courses 1, 3, and 5 (dose: 250 micrograms/m²/dose); monoclonal antibody Ch14.18 IV over 10 hours on days 3-6 of courses 1, 3, and 5 and on days 7-10 of courses 2 and 4 (dose: 25 mg/m2/dose); and oral isotretinoin twice daily on days 11-24 of course 1, on days 14-27 of courses 2, 4, and 6, and on days 10-23 of courses 3 and 5 (Weight based dosage: > 12 kg: 80 mg/m2/dose BID; total daily dose 160 mg/m2/day, divided BID. ≤ 12 kg: 2.67 mg/kg/dose BID; total daily dose is 5.33 mg/kg/day, divided BID. Round dose up to the nearest 10 mg). Patients also receive aldesleukin IV continuously on days 0-3 and on days 7-10 of courses 2 and 4 (actual dosage is body surface area based and varies by course). Treatment repeats every 24-32 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Given IV - Doses and days vary by week of course:
Week 1 of Each Course: Dose: 3 Million International Units/m2/dose. Days: 0-3. Week 2 of Each Course: Dose: 4.5 Million International Units/m2/dose. Days: 7-10. Actual dosage is Body Surface Area calculated.
Other Names:Biological: sargramostim
Given IV or SC
Other Names:Biological: monoclonal antibody Ch14.18
Other Names:Drug: isotretinoin
I. To comprehensively define the safety profile of monoclonal antibody Ch14.18 when administered with sargramostim, aldesleukin, and isotretinoin after autologous stem cell transplantation (ASCT) in patients with high-risk neuroblastoma.
I. To further describe and refine the event-free survival and overall survival estimates in patients treated with this regimen.
II. To further describe the baseline characteristics of patients treated with these regimen.
III. To further describe the safety and toxicity of this regimen, in terms of number of courses delivered per patient, number of dose reductions or stoppage, and number of toxic deaths, in these patients.
IV. To further describe the immune reconstitution following ASCT based on laboratory data obtained just before, during, and after treatment with this regimen.
V. To obtain correlative laboratory data to evaluate and describe mechanisms related to response, toxicity of immune activation, and allergic phenomena.
OUTLINE: This is a multicenter study.
Patients receive sargramostim subcutaneously or IV over 2 hours on days 0-13 of courses 1, 3, and 5; monoclonal antibody Ch14.18 IV over 10 hours on days 3-6 of courses 1, 3, and 5 and on days 7-10 of courses 2 and 4; and oral isotretinoin twice daily on days 11-24 of course 1, on days 14-27 of courses 2, 4, and 6, and on days 10-23 of courses 3 and 5. Patients also receive aldesleukin IV continuously on days 0-3 and on days 7-10 of courses 2 and 4. Treatment repeats every 24-32 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Patients may undergo blood and bone marrow sample collection periodically for correlative laboratory studies.
After completion of study therapy, patients are followed up every 3 months for 1 year, every 6 months for 4 years, and then annually thereafter.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01041638
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|Principal Investigator:||Mehmet Ozkaynak, MD||Children's Oncology Group|