Dinutuximab, Sargramostim, and Combination Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma Undergoing Stem Cell Transplant
|ClinicalTrials.gov Identifier: NCT03786783|
Recruitment Status : Recruiting
First Posted : December 25, 2018
Last Update Posted : September 10, 2019
|Condition or disease||Intervention/treatment||Phase|
|Ganglioneuroblastoma High-Risk Neuroblastoma NMYC Gene Amplification||Biological: Aldesleukin Procedure: Autologous Hematopoietic Stem Cell Transplantation Drug: Carboplatin Drug: Cisplatin Drug: Cyclophosphamide Drug: Dexrazoxane Biological: Dinutuximab Drug: Doxorubicin Drug: Etoposide Radiation: External Beam Radiation Therapy Drug: Isotretinoin Drug: Melphalan Biological: Sargramostim Drug: Thiotepa Drug: Topotecan Drug: Vincristine||Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||45 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Induction Regimen Incorporating Chimeric 14.18 Antibody (ch14.18, Dinutuximab) (NSC# 764038) and Sargramostim (GM-CSF) for the Treatment of Newly Diagnosed High-Risk Neuroblastoma|
|Actual Study Start Date :||January 14, 2019|
|Estimated Primary Completion Date :||July 31, 2021|
|Estimated Study Completion Date :||July 31, 2021|
Experimental: Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
See Detailed Description
Procedure: Autologous Hematopoietic Stem Cell Transplantation
Radiation: External Beam Radiation Therapy
- Incidence of adverse events [ Time Frame: Up to 63 days ]Assessed with National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. A one-sided Pocock group-sequential boundary with a sample size of 42 will be used to monitor the number of patients who experience at least one unacceptable toxicity during cycle 3-5 of induction. Will be assessed by the unacceptable toxicity monitoring rule and by the estimation of the combined toxic death and unacceptable toxicity rate together with a 95% confidence interval (CI).
- Proportion of patients who are classified as a "failure" [ Time Frame: Up to 5 years ]Feasibility "failures" are defined as patients that do not receive >= 75% of the planned dinutuximab doses during Induction. A one-sided Pocock group-sequential boundary with a sample size of 42 will be used to monitor the number of patients deemed feasibility "failures" during cycle 3-5 of induction. Will be assessed by the monitoring rule and, in addition, by estimation of the feasibility "failure" rate together with a 95% CI. The therapy will be deemed feasible at the specified dose level if the feasibility monitoring rule is not triggered.
- Response rate [ Time Frame: Up to 5 years ]Response will be determined using the revised International Neuroblastoma Response Criteria. Response rate will be calculated as the percentage of eligible patients with at least a partial response (PR) or better at the end of Induction and will also be considered in determining whether the regimen is worth further study. Will be calculated, including placement of a 95% CI on the response rate.
- Event-free survival [ Time Frame: From study enrollment to the occurrence of disease relapse or progression, secondary malignancy, or death, assessed from baseline up to 5 years ]Kaplan-Meier curves will be generated.
- Overall survival [ Time Frame: From study enrollment to death, assessed from baseline up to 5 years ]Kaplan-Meier curves will be generated.
- Incidence of naturally occurring anti-glycan antibodies [ Time Frame: Up to 5 years ]Will be calculated, including placement of a 95% CI on the incidence. In addition, anti-glycan levels prior to the start of Induction therapy and prior to the start of post-Consolidation therapy will be compared with Wilcoxon's signed-rank test for paired data.
- Incidence of natural killer (NK) receptor NKp30 isoforms [ Time Frame: Up to 5 years ]Will be assessed by calculating the incidence of NK receptor NKp30 isoforms, including placement of a 95% CI on the incidence.
- Response of host factors, including naturally occurring anti-glycan antibodies, KIR/KIR-L genotyping, Fc receptor genotyping, human anti-chimeric antibodies (HACA) [ Time Frame: Up to 5 years ]Will be explored with Fisher's exact test for categorical and Wilcoxon rank-sum test for continuous host factors. Both the presence/absence and level of naturally occurring anti-glycan antibodies will be considered. For the KIR/KIR-L analysis, patients will be categorized as either matched or mismatched. Patients will be grouped into one of the three genotype subgroups of Fc receptor genotyping for that analysis. The presence/absence of HACA, anti-idiotype, and pretreatment anti-therapeutic antibodies (PATA)/anti-allotype antibody will be considered for the HACA analysis.
- Immune environment (gene expression; immune effector cells, activities and signaling molecules; immune target expression) [ Time Frame: Up to 5 years ]The incidence of NK receptor NKp30 isoforms will be calculated, including placement of a 95% CI on each incidence rate. Summary statistics will also be generated for serum cytokine (IL6, CXCL9) levels and gene expression of circulating immune function cells.
- Levels of circulating GD2 and tumor cell GD2 expression [ Time Frame: Up to 5 years ]Will be assessed by exploring the relationship between response to treatment with > PR (response vs. non- response) with circulating GD2 levels, and GD2 tumor cell expression following therapy with a Wilcoxon rank-sum test. Changes from baseline will also be analyzed.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03786783
|United States, California|
|Children's Hospital Los Angeles||Recruiting|
|Los Angeles, California, United States, 90027|
|Contact: Site Public Contact 323-361-4110|
|Principal Investigator: Leo Mascarenhas|
|United States, District of Columbia|
|Children's National Medical Center||Recruiting|
|Washington, District of Columbia, United States, 20010|
|Contact: Site Public Contact 202-884-2549|
|Principal Investigator: Jeffrey S. Dome|
|United States, Massachusetts|
|Dana-Farber Cancer Institute||Recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: Site Public Contact 877-442-3324|
|Principal Investigator: Suzanne Shusterman|
|United States, Pennsylvania|
|Children's Hospital of Pittsburgh of UPMC||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15224|
|Contact: Site Public Contact 412-692-8570 firstname.lastname@example.org|
|Principal Investigator: Jean M. Tersak|
|United States, Tennessee|
|St. Jude Children's Research Hospital||Recruiting|
|Memphis, Tennessee, United States, 38105|
|Contact: Site Public Contact 866-278-5833 email@example.com|
|Principal Investigator: Sara M. Federico|
|United States, Utah|
|Primary Children's Hospital||Recruiting|
|Salt Lake City, Utah, United States, 84113|
|Contact: Site Public Contact 801-585-5270|
|Principal Investigator: Phillip E. Barnette|
|Australia, New South Wales|
|The Children's Hospital at Westmead||Recruiting|
|Westmead, New South Wales, Australia, 2145|
|Contact: Site Public Contact 61-2-9845 1400|
|Principal Investigator: Bhavna Padhye|
|Royal Children's Hospital||Recruiting|
|Parkville, Victoria, Australia, 3052|
|Contact: Site Public Contact 61 3 9345 5656 Jordan.Hansford@rch.org.au|
|Principal Investigator: Bhavna Padhye|
|Starship Children's Hospital||Recruiting|
|Grafton, Auckland, New Zealand, 1145|
|Contact: Site Public Contact 0800 728 436|
|Principal Investigator: Andrew C. Wood|
|Principal Investigator:||Sara M Federico||Children's Oncology Group|