Autologous Transplant Followed by Allogeneic Transplant for High Risk Neuroblastoma

• Status: Terminated
• Trial end date: 2010-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Neuroblastoma is a malignant tumor of the sympathetic nervous system. It is the second most common malignant tumor of childhood. Although modest advances have been made over the past 20 years children with high-risk neuroblastoma continue to have an unsatisfactory long-term survival. This study will administer induction chemotherapy followed by high-dose (myeloablative) chemotherapy with autologous stem cell transplantation, followed by radiation therapy, then immunotherapy with a non myeloablative allogeneic stem cell transplant for treatment of neuroblastoma. The purpose of this clinical research trial is to study the feasibility of giving immunotherapy with a non-myeloablative allogeneic transplant (NAT/AlloSCT), following myeloablative therapy and autologous stem cell transplant (MAT/AutoSCT). This study will also determine the side effects as well as the response rate for each group of patients (treatment arm).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Columbia University
• Treatments: Busulfan; Fludarabine; Fludarabine phosphate; Thymoglobulin; Vidarabine

Criteria

Inclusion Criteria:

• Age be < 30 years of age at the time of initial diagnosis.

• Patients must have a diagnosis of neuroblastoma (ICD-O morphology 9500/3) verified by histology and/or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites. Patients with the following disease stages at diagnosis are eligible, if they meet the other specified criteria. The revised International Neuroblastoma Staging System (INSS) will be used to stage all patients

58. (See 14.3 for risk assignment).

• Patients with newly diagnosed neuroblastoma and age > 547 days with the following:

• INSS Stage 4 neuroblastoma regardless of biologic factors

• INSS Stage 2A/2B with MYCN amplification (> 10)

• INSS Stage 3 with MYCN amplification (> 10) OR Unfavorable histology

• Patients with newly diagnosed neuroblastoma and age < 365 days with the following:

• INSS Stage 3, 4, OR 4S neuroblastoma AND MYCN amplification (> 10).

• Patients with newly diagnosed Neuroblastoma and age 365 - <547 days with the following:

• INSS Stage 3 with MYCN amplification (> 10)

• INSS Stage 4 with MYCN amplification (> 10) OR with deoxyribonucleic acid (DNA) Index (ploidy) = 1 OR with Unfavorable histology

• Patients > 365 days with INSS Stage 1, 2, and 4S who have progressed to Stage 4.

• Newly Diagnosed patients should be entered on this study within 4 weeks of diagnosis, or after receiving only one cycle of intermediate dose chemotherapy for patients initially treated on/according to the low or intermediate risk Children's Oncology Group (COG) neuroblastoma studies, or within 4 weeks of progression to Stage 4 for INSS Stage 1, 2, 4S.

• Patients treated with alternative induction regimens and/or consolidation regimens (AutoSCT) who were not enrolled at diagnosis but who achieve a complete response (CR), very good partial response (VGPR), partial response (PR), or minimal response (MR) and meet all other criteria will be eligible for either the consolidation MAT/AutoSCT and NAT/AlloSCT immunotherapy or NAT/AlloSCT, which ever is clinically appropriate after discussion with the Principal Investigators.

• Liver Function: alanine aminotransferase (ALT) and bilirubin < 3x normal

• Cardiac Function: Shortening fraction > 27%, or ejection fraction > 47%, no clinical congestive heart failure.

• Renal Function: Creatinine clearance and/or glomerular filtration rate (GFR) > 60 ml/min/1.73m2.

• Hematologic Function: Patients must have adequate hematopoietic function (absolute neutrophil count (ANC) > 1000/mm3 and platelets > 100,000/mm3) unless inadequate hematopoiesis documented to be due to bone marrow involvement with tumor (> 10% tumor infiltration).

Exclusion Criteria:

• Patients who are pregnant. Patients of childbearing potential must practice an effective method of birth control while participating on this study.