This phase III trial is studying the side effects of giving monoclonal antibody Ch14.18 together with sargramostim, aldesleukin, and isotretinoin after autologous stem cell transplant in treating patients with neuroblastoma. Monoclonal antibodies, such as Ch14.18, may find tumor cells and help kill them. Colony-stimulating factors, such as sargramostim, may increase the number of immune cells found in bone marrow or peripheral blood. Aldesleukin may stimulate the white blood cells to kill tumor cells. Isotretinoin may help neuroblastoma cells become more like normal cells, and to grow and spread more slowly. Giving monoclonal antibody Ch14.18 with sargramostim, aldesleukin, and isotretinoin after autologous stem cell transplant may be an effective treatment for neuroblastoma.
PRIMARY OBJECTIVES: I. To comprehensively define the safety profile of ch14.18 when administered with cytokines and isotretinoin in high-risk neuroblastoma patients after autologous stem cell transplant (ASCT). SECONDARY OBJECTIVES: I. To further describe and refine the event-free survival (EFS) and overall survival (OS) estimates and baseline characteristics for subjects receiving chl4.18 + cytokines + isotretinoin. II. To further describe the safety and toxicity of chl4.18 + cytokines + isotretinoin with focus on: a) number of courses delivered per patient; b) number of dose reductions or stoppage (ch14.18 and/or interleukin \[IL\]-2 \[aldesleukin\]); and c) number of toxic deaths. III. To further describe the immune reconstitution of patients following ASCT, based on laboratory data obtained just prior to, during, and after treatment with this regimen. IV. To obtain correlative laboratory data to evaluate and describe mechanisms related to response, toxicity of immune activation, and allergic phenomena. OUTLINE: Patients receive sargramostim subcutaneously (SC) or intravenously (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 isotretinoin orally (PO) twice daily (BID) 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. 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
105
Given IV
Correlative studies
Given IV
Given PO
Given IV or SC
Loma Linda University Medical Center
Loma Linda, California, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Children's Hospital of Orange County
Orange, California, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States
Rady Children's Hospital - San Diego
San Diego, California, United States
Percentage of Patients Who Experienced a Significant (CTC Grade 3-5) Nonhematologic Toxicity of Interest (Pain, Hypotension, Allergic Reactions, Capillary Leak Syndrome, or Fever).
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.
Time frame: Up to 6 courses of therapy
Event-free Survival (EFS)
Event-free Survival (EFS) for all eligible patients enrolled on the study
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 3 years
Overall Survival (OS)
Overall Survival (OS) for all eligible patients enrolled on the study
Time frame: From enrollment until death, or until last contact with the patient, up to 3 years
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