Phase 3
N=665
Comparing Two Different Myeloablation Therapies in Treating Young Patients Who Are Undergoing a Stem Cell Transplant for High-Risk Neuroblastoma
Localized Resectable Neuroblastoma · Localized Unresectable Neuroblastoma · Recurrent Neuroblastoma · Regional Neuroblastoma · Stage 4 Neuroblastoma
Bottom Line
View on ClinicalTrials.gov: NCT00567567 ↗Enrolled (actual)
665
Serious AEs
6.6%
Results posted
Jun 2017
Primary outcome: Primary: Event-free Survival Rate — 48.8; 61.8 percent probability — p=0.0082
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Autologous Hematopoietic Stem Cell Transplantation (Procedure); Carboplatin (Drug); Cisplatin (Drug); Cyclophosphamide (Drug); Doxorubicin Hydrochloride (Drug); Etoposide (Drug); External Beam Radiation Therapy (Radiation); Filgrastim (Biological); Isotretinoin (Drug); Laboratory Biomarker Analysis (Other); Melphalan (Drug); Peripheral Blood Stem Cell Transplantation (Procedure); Pharmacological Study (Other); Thiotepa (Drug); Topotecan Hydrochloride (Drug); Vincristine Sulfate Liposome (Drug)
- Age
- Pediatric, Adult
- Sex
- All
- Sponsor
- Children's Oncology Group
- Primary completion
- Feb 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Event-free Survival Rate |
48.8; 61.8 | 0.0082 sig |
| PRIMARY Response After Induction Therapy |
0.54; 0.48; 0.35 | 0.0034 sig |
| PRIMARY Incidence Rate of Local Recurrence |
15.7 | 0.5615 |
| SECONDARY Duration of Greater Than or Equal to Grade 3 Neutropenia |
7; 7; 7 | 0.0939 |
| SECONDARY Duration of Greater Than or Equal to Grade 3 Thrombocytopenia |
4; 4; 4 | 0.3277 |
| SECONDARY Proportion of Patients With a Polymorphism |
0.96; 0.96; 0.97 | 0.7598 |
| SECONDARY Surgical Response |
83.98; 84.09; 58.89 | — |
| SECONDARY Type of Surgical or Radiotherapy Complication |
13.11; 12.50; 11.85 | — |
| SECONDARY Intraspinal Extension |
8.25; 9.66; 7.78 | — |
| SECONDARY Peak Serum Concentration of Isotretinoin in Patients Enrolled on Either A3973, ANBL0032, ANBL0931, ANBL0532 and Future High Risk Studies |
1.00; 1.36; 1.26 | 0.6853 |
| SECONDARY Pharmacogenetic Variants in Patients Enrolled on Either A3973, ANBL0032, ANBL0931, ANBL0532 and Future High Risk Studies |
— | — |
| SECONDARY Topotecan Systemic Clearance |
28.1; 28.1; 28.5 | — |
| SECONDARY Presence and Function of T Cells Capable of Recognizing Neuroblastoma |
— | — |
| SECONDARY Enumeration of Peripheral Blood Cluster of Differentiation (CD)3, CD4, and CD8 Cells |
200; 255.5; 73; 81; 104; 151 | — |
| SECONDARY Proportion of Patients With Neuroblastoma Detected in Bone Marrow and Peripheral Blood Using RT-PCR Technique |
— | — |
| SECONDARY EFS Pts Non-randomly Assigned to Single CEM (12-18 Mths, Stg. 4, MYCN Nonamplified Tumor/Unfavorable or Indeterminant Histopathology/Diploid DNA Content & Pts>547 Days, Stg.3, MYCN Nonamplified Tumor AND Unfavorable or Indeterminant Histopathology). |
73.1 | — |
| SECONDARY OS in Patients 12-18 Months, Stage 4, MYCN Nonamplified Tumor/Unfavorable Histopathology/Diploid DNA Content/Indeterminant Histology/Ploidy and Patients > 547 Days, Stage 3, MYCN Nonamplified Tumor AND Unfavorable Histopathology/Indeterminant Histology |
81.0 | — |
Summary
This randomized phase III trial compares two different high-dose chemotherapy regimens followed by a stem cell transplant in treating younger patients with high-risk neuroblastoma. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments before a peripheral blood stem cell transplant helps kill any tumor cells that are in the body and helps make room in the patient?s bone marrow for new blood-forming cells (stem cells) to grow. After treatment, stem cells are collected from the patient's blood and stored. High-dose chemotherapy and radiation therapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the high- chemotherapy. It is not yet known which regimen of high-dose chemotherapy is more effective for patients with high-risk neuroblastoma undergoing a peripheral blood stem cell transplant.
Eligibility Criteria
Inclusion Criteria
- Diagnosis of neuroblastoma or ganglioneuroblastoma by histology or as evidenced by the presence of clumps of tumor cells in bone marrow and elevated catecholamine metabolites in urine meeting any of the following criteria:
- Patients with newly diagnosed neuroblastoma with International Neuroblastoma Staging System (INSS) stage 4 disease are eligible with the following:
- MYCN amplification (i.e., greater than four-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features
- Age > 18 months (i.e., > 547 days) regardless of biologic features
- Age 12-18 months (i.e., 365-547 days) with none of the following three favorable biologic features (i.e., non-amplified MYCN, favorable pathology, and deoxyribonucleic acid [DNA] index > 1)
- Patients with newly diagnosed neuroblastoma with INSS stage 3 are eligible with the following:
- MYCN amplification (i.e., greater than four-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features
- Age > 18 months (i.e., > 547 days) with unfavorable pathology, regardless of MYCN status
- Patients with newly diagnosed INSS stage 2a or 2b with MYCN amplification (i.e., greater than four-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features
- Patients with newly diagnosed INSS stage 4s with MYCN amplification (i.e., greater than four-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features
- Patients >= 365 days initially diagnosed with INSS stage 1, 2, or 4S and who progressed to a stage 4 without interval chemotherapy
- Must have been enrolled on COG-ANBL00B1
- Creatinine clearance or radioisotope glomerular filtration rate ? 70mL/min OR serum creatinine based on age/gender as follows:
- 1 month to = 16 years: 1.7 mg/dL (male), 1.4 mg/dL (female)
- Total bilirubin ? 1.5 times upper limit of normal (ULN) for age
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) = 27% by echocardiogram (ECHO) OR left ventricular ejection fraction (LVEF) >= 50% by radionuclide angiogram
- No known contraindication (e.g., size, weight or physical condition) to peripheral blood stem cell collection
- No prior systemic therapy except for localized emergency radiation to sites of life-threatening or function-threatening disease
- No more than one course of chemotherapy per low- or intermediate-risk neuroblastoma therapy prior to determination of MYCN amplification and histology
Data sourced from ClinicalTrials.gov (NCT00567567). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.