Busulfan, Melphalan, and Stem Cell Transplant After Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma
|ClinicalTrials.gov Identifier: NCT01798004|
Recruitment Status : Suspended (CRM: 31684 - CTEP PIO requested)
First Posted : February 25, 2013
Results First Posted : February 9, 2017
Last Update Posted : March 17, 2017
|Condition or disease||Intervention/treatment||Phase|
|Disseminated Neuroblastoma Localized Resectable Neuroblastoma Localized Unresectable Neuroblastoma Regional Neuroblastoma Stage 4S Neuroblastoma||Drug: cyclophosphamide Drug: topotecan hydrochloride Drug: cisplatin Drug: etoposide Drug: vincristine sulfate Drug: doxorubicin hydrochloride Radiation: external beam radiation therapy Drug: busulfan Drug: melphalan Procedure: autologous hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Other: pharmacological study Other: laboratory biomarker analysis Biological: filgrastim Drug: mesna||Not Applicable|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||150 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pilot Study Using Myeloablative Busulfan/Melphalan (BuMel) Consolidation Following Induction Chemotherapy for Patients With Newly Diagnosed High-Risk Neuroblastoma|
|Study Start Date :||April 2013|
|Actual Primary Completion Date :||July 2015|
|Estimated Study Completion Date :||October 2018|
U.S. FDA Resources
Experimental: Treatment (induction therapy, consolidation therapy, ASCT)
COURSES 1-2: Patients receive cyclophosphamide IV over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Treatment repeats every 3 weeks for 2 courses.
COURSES 3 AND 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide IV over 1-2 hours on days 1-3. Treatment repeats every 3 weeks for 2 courses.
COURSE 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2, vincristine sulfate IV over 1 minute on days 1-3, and doxorubicin hydrochloride IV over 24 hours on days 1-3. Treatment repeats every 3 weeks for 1 course.
Treatment continues in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Beginning 4-8 weeks following the 5th course of induction therapy, patients receive busulfan IV over 3 hours on days -6 to -3 and melphalan IV on day -1. Patients undergo ASCT on day 0.
Some patients also undergo EBRT after induction and consolidation.
Other Names:Drug: topotecan hydrochloride
Other Names:Drug: cisplatin
Other Names:Drug: etoposide
Other Names:Drug: vincristine sulfate
Other Names:Drug: doxorubicin hydrochloride
Other Names:Radiation: external beam radiation therapy
Other Name: EBRTDrug: busulfan
Other Names:Drug: melphalan
Other Names:Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous peripheral blood stem cell transplantProcedure: peripheral blood stem cell transplantation
Undergo autologous peripheral blood stem cell transplant
Other Names:Other: pharmacological study
Other Name: pharmacological studiesOther: laboratory biomarker analysis
Optional correlative studiesBiological: filgrastim
Given SC or IV
Other Names:Drug: mesna
- The Tolerability of BuMel Regimen [ Time Frame: Up to 28 days post-consolidation therapy, up to 1 year ]Number of patients who experience one or more unacceptable toxicities (severe sinusoidal obstruction syndrome [SOS] or Grade 4-5 pulmonary toxicity per Common Toxicity Criteria [CTC] v.4.0) during the Consolidation phase of therapy.
- Incidence of Non-hematologic Organ Toxicity (Grade 3 and Higher) and All Cause Mortality Graded According to CTC v4.0 [ Time Frame: Up to 180 days ]Assessed by a descriptive analysis of the incidence of grade 3-5 non-hematologic toxicities (CTC v4.0) and all-cause mortality during consolidation therapy. In addition, a descriptive analysis of "late" onset grade 4-5 pulmonary and hepatic complications that occur within 180 days of the start of consolidation therapy will be examined, regardless if the patient has proceeded to other therapy (including chimeric antibody) during that 180 day period.
- Response Rate Determined Using the International Response Criteria [ Time Frame: Up to 5 years ]
- EFS [ Time Frame: Up to 5 years ]
- Overall Survival [ Time Frame: Up to 5 years ]
- First Dose Area Under the Curve (AUC) and Average Daily AUC for Busulfan [ Time Frame: Within 28 days following consolidation ]Relationship with occurrence of non-hematologic toxicities assessed by a descriptive analysis. Association between busulfan exposure levels as measured by the area under the curve (AUC) and event-free survival and overall survival will be examined using Cox proportional hazards models.
- Percentage of Centrally Reviewed Post-course 4 MIBG Scans Reporting a Curie Score Considered to Have Been Determined in "Real Time" [ Time Frame: Up to week 12 (course 4 of induction therapy) ]
- Percentage of MIBG Scans Receiving Institutionally and Centrally Reviewed and Automated Advanced Assisted Scoring Platform Curie Scores Within 1 Unit of Each Other [ Time Frame: Up to week 12 (course 4 of induction therapy) ]Cohen's kappa will be calculated to evaluate the concordance in Curie scores between each of the scoring methods at each time point. Up to 160 MIBG scans are expected at diagnosis and up to 144 MIBG scans from the 90% of patients estimated to be MIBG avid are projected post-course 4 of induction therapy, for a total of up to 304 MIBG scans.
- Proportion of High-risk Neuroblastoma Patients for Whom ALK Status Can be Obtained [ Time Frame: Within 6 weeks of diagnosis ]
- Proportion of High-risk Neuroblastoma Patients With MYCN Non-amplified Tumors for Whom Molecular Profiling Results Can be Obtained [ Time Frame: Within 8 weeks of diagnosis ]
- Melphalan Pharmacokinetics and the Combination of Busulfan and Melphalan AUC (Optional) [ Time Frame: Within 28 days post-consolidation ]A descriptive analysis of the relationship between melphalan pharmacokinetics and the combination of busulfan and melphalan AUC with the occurrence of non-hematologic toxicities within 28 days following completion of consolidation will be assessed. In addition, the association between melphalan exposure levels as measured by the AUC and event-free survival and overall survival will be examined using Cox proportional hazards models.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01798004
Show 121 Study Locations
|Principal Investigator:||Mary Meaghan Granger, MD||Children's Oncology Group|