Dinutuximab, Sargramostim, and Combination Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma Undergoing Stem Cell Transplant
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03786783|
Recruitment Status : Active, not recruiting
First Posted : December 26, 2018
Last Update Posted : September 16, 2020
|Condition or disease||Intervention/treatment||Phase|
|Ganglioneuroblastoma High Risk Neuroblastoma||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|
|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 :||June 30, 2021|
|Estimated Study Completion Date :||June 30, 2021|
Experimental: Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT)
See Detailed Description
Procedure: Autologous Hematopoietic Stem Cell Transplantation
Radiation: External Beam Radiation Therapy
- Incidence of unacceptable toxicity [ Time Frame: Up to the first 5 cycles of treatment ]Assessed with National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Will be assessed by estimation of the combined toxic death and unacceptable toxicity rate during Induction cycles 3-5 together with a 95% confidence interval.
- Proportion of patients who are feasibility "failure" [ Time Frame: Up to the first 5 cycles of treatment ]Feasibility "failures" are defined as patients that do not receive >= 75% of the planned dinutuximab doses during Induction cycles 3-5. Will be assessed by estimation of the feasibility "failure" rate together with a 95% confidence interval.
- Response rate [ Time Frame: Up to the first 5 cycles of treatment ]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. Will be calculated, including placement of a 95% confidence interval on the response rate.
- Event-free survival [ Time Frame: Up to 5 years ]Kaplan-Meier method will be used to estimate event-free survival (EFS). EFS is defined as the time from study enrollment to the occurrence of disease relapse or progression, secondary malignancy, or death.
- Overall survival [ Time Frame: Up to 5 years ]Kaplan-Meier method will be used to estimate overall survival (OS). OS is defined as the time from study enrollment to death.
- 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|
|Los Angeles, California, United States, 90027|
|United States, District of Columbia|
|Children's National Medical Center|
|Washington, District of Columbia, United States, 20010|
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|United States, New York|
|NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center|
|New York, New York, United States, 10032|
|United States, Pennsylvania|
|Children's Hospital of Pittsburgh of UPMC|
|Pittsburgh, Pennsylvania, United States, 15224|
|United States, Tennessee|
|Saint Jude Children's Research Hospital|
|Memphis, Tennessee, United States, 38105|
|United States, Utah|
|Primary Children's Hospital|
|Salt Lake City, Utah, United States, 84113|
|Australia, New South Wales|
|The Children's Hospital at Westmead|
|Westmead, New South Wales, Australia, 2145|
|Royal Children's Hospital|
|Parkville, Victoria, Australia, 3052|
|Starship Children's Hospital|
|Grafton, Auckland, New Zealand, 1145|
|Principal Investigator:||Sara M Federico||Children's Oncology Group|