Dinutuximab, Sargramostim, and Combination Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma Undergoing Stem Cell Transplant
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|ClinicalTrials.gov Identifier: NCT03786783|
Recruitment Status : Recruiting
First Posted : December 25, 2018
Last Update Posted : August 13, 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
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|