Clinical trial · Interventional
Comparing Two Different Myeloablation Therapies in Treating Young Patients Who Are Undergoing a Stem Cell Transplant for High-Risk Neuroblastoma
Phase III Randomized Trial of Single vs. Tandem Myeloablative Consolidation Therapy for High-Risk Neuroblastoma
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (6)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Localized Resectable Neuroblastoma | Neuroblastoma | CURATED_BROADER | 0.78 |
| Localized Unresectable Neuroblastoma | Neuroblastoma | CURATED_BROADER | 0.78 |
| Recurrent Neuroblastoma | Neuroblastoma | CURATED_BROADER | 0.78 |
| Regional Neuroblastoma | Regional Neuroblastoma | ONTOLOGY_EXACT | 0.98 |
| Stage 4 Neuroblastoma | — | UNRESOLVED | — |
| Stage 4S Neuroblastoma | — | UNRESOLVED | — |
Interventions
Interventions (16)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Autologous Hematopoietic Stem Cell Transplantation | Procedure | — | UNRESOLVED |
| Carboplatin | Drug | Carboplatin | ALIAS |
| Cisplatin | Drug | Cisplatin | ALIAS |
| Cyclophosphamide | Drug | Cyclophosphamide | ALIAS |
| Doxorubicin Hydrochloride | Drug | Doxorubicin | ALIAS |
| Etoposide | Drug | Etoposide | ALIAS |
| External Beam Radiation Therapy | Radiation | — | UNRESOLVED |
| Filgrastim | Biological | Filgrastim | ALIAS |
Design
Arms and outcomes
Arms (2)
- type
- ACTIVE_COMPARATOR
- label
- Consolidation Arm A: single myeloablative consolidation
- description
- Patients receive melphalan IV over 15-30 minutes on days -7 to -5, etoposide IV over 24 hours and carboplatin IV over 24 hours on days -7 to -4, and G-CSF SC or IV beginning on day 0 and continuing until blood counts recover. Patients undergo autologous PBSCT on day 0.
- interventionNames
- Procedure: Autologous Hematopoietic Stem Cell Transplantation
- Drug: Carboplatin
- Drug: Cisplatin
- Drug: Cyclophosphamide
- Drug: Doxorubicin Hydrochloride
- Drug: Etoposide
- Radiation: External Beam Radiation Therapy
- Biological: Filgrastim
- Drug: Isotretinoin
- Other: Laboratory Biomarker Analysis
- Drug: Melphalan
- Procedure: Peripheral Blood Stem Cell Transplantation
- Other: Pharmacological Study
- Drug: Topotecan Hydrochloride
- Drug: Vincristine Sulfate Liposome
- type
- EXPERIMENTAL
- label
Eligibility
Eligibility (as posted)
- Sex
- All
- Maximum age
- 30 Years
Show eligibility criteria text
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 \< 6 months: 0.4 mg/dL
* 6 months to \< 1 year: 0.5 mg/dL
* 1 to \< 2 years: 0.6 mg/dL
* 2 to \< 6 years: 0.8 mg/dL
* 6 to \< 10 years: 1 mg/dL
* 10 to \< 13 years: 1.2 mg/dL
* 10 to \< 16 years: 1.5 mg/dL (male), 1.4 mg/dL (female)
* \>= 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) \< 10 times ULN for age
* Not pregnant or nursing
* Negative pregnancy test
* Shortening fraction \>= 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 histologyReferences
Publications (3)
- DERIVEDBerko ER, Naranjo A, Daniels AA, McNulty SN, Krytska K, Druley T, Zelley K, Koneru B, Chen L, Polkosnik G, Irwin MS, Bagatell R, Maris JM, Reynolds CP, DuBois SG, Park JR, Mosse YP. Frequency and Clinical Significance of Clonal and Subclonal Driver Mutations in High-Risk Neuroblastoma at Diagnosis: A Children's Oncology Group Study. J Clin Oncol. 2025 May 10;43(14):1673-1684. doi: 10.1200/JCO-24-02407. Epub 2025 Mar 4. PMID 40036726
- DERIVEDLiu KX, Naranjo A, Zhang FF, DuBois SG, Braunstein SE, Voss SD, Khanna G, London WB, Doski JJ, Geiger JD, Kreissman SG, Grupp SA, Diller LR, Park JR, Haas-Kogan DA. Prospective Evaluation of Radiation Dose Escalation in Patients With High-Risk Neuroblastoma and Gross Residual Disease After Surgery: A Report From the Children's Oncology Group ANBL0532 Study. J Clin Oncol. 2020 Aug 20;38(24):2741-2752. doi: 10.1200/JCO.19.03316. Epub 2020 Jun 12. PMID 32530765
- DERIVEDPark JR, Kreissman SG, London WB, Naranjo A, Cohn SL, Hogarty MD, Tenney SC, Haas-Kogan D, Shaw PJ, Kraveka JM, Roberts SS, Geiger JD, Doski JJ, Voss SD, Maris JM, Grupp SA, Diller L. Effect of Tandem Autologous Stem Cell Transplant vs Single Transplant on Event-Free Survival in Patients With High-Risk Neuroblastoma: A Randomized Clinical Trial. JAMA. 2019 Aug 27;322(8):746-755. doi: 10.1001/jama.2019.11642. PMID 31454045