Ignite Creation Date:
2024-05-05 @ 11:23 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00026312
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-07-15
First Post:
2001-11-09
Brief Title:
Isotretinoin With or Without Dinutuximab Aldesleukin and Sargramostim Following Stem Cell Transplant in Treating Patients With Neuroblastoma
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
Phase III Randomized Study of Chimeric Antibody 1418 Ch1418 in High Risk Neuroblastoma Following Myeloablative Therapy and Autologous Stem Cell Rescue
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This partially randomized phase III trial studies isotretinoin with dinutuximab aldesleukin and sargramostim to see how well it works compared to isotretinoin alone following stem cell transplant in treating patients with neuroblastoma Drugs used in chemotherapy such as isotretinoin work in different ways to stop the growth of tumor cells either by killing the cells by stopping them from dividing or by stopping them from spreading Monoclonal antibodies such as dinutuximab may block tumor growth in different ways by targeting certain cells Aldesleukin and sargramostim may stimulate a persons white blood cells to kill cancer cells It is not yet known if chemotherapy is more effective with or without dinutuximab aldesleukin and sargramostim following stem cell transplant in treating neuroblastoma
Detailed Description:
PRIMARY OBJECTIVES
I Determine if monoclonal antibody Ch1418 dinutuximab cytokines isotretinoin 13-cis-retinoic acid or RA improves event free survival after myeloablative therapy and stem cell rescue as compared to RA alone in high risk neuroblastoma patients who have achieved a pre-autologous stem cell transplant ASCT response of complete response CR very good partial response VGPR or partial response PR
SECONDARY OBJECTIVES
I Determine if monoclonal antibody Ch1418 cytokines isotretinoin 13-cis-retinoic acid or RA improves overall survival after myeloablative therapy and stem cell rescue as compared to RA alone in high risk neuroblastoma patients who have achieved a pre-ASCT response of CR VGPR or PR
II Determine if immunotherapy RA improves event free survival and overall survival as compared to RA alone in the subgroup of high risk International Neuroblastoma Staging System INSS stage 4 neuroblastoma patients who have achieved a pre-ASCT response of CR VGPR or PR
III Determine the toxicities of the combination of monoclonal antibody Ch1418 with cytokines
IV To compare the outcome data of the patients with persistent disease documented by biopsy Stratum 07 to the historical data for the analogous patients from Childrens Cancer Group CCG-3981
V To further describe and refine the event free survival EFS and overall survival OS estimates and baseline characteristics for subjects receiving Ch1418 cytokines RA following cessation of the randomized portion of the study
VI To further describe the safety and toxicity of Ch1418 cytokines RA under the new administration guidelines implemented following cessation of the randomized portion of the study with focus on a number of courses delivered per subject b number of dose reductions or stoppage ch1418 andor interleukin IL-2 and c number of toxic deaths
TERTIARY OBJECTIVES
I In the subgroup of neuroblastoma patients who have achieved a pre-ASCT response of CR VGPR or PR determine if there is a difference between the two randomized regimens in reducing the minimal residual disease MRD burden as detected by the following parameters meta-iodobenylguanidine MIBG scan immunocytology IC of blood and bone marrow samples reverse transcriptase-polymerase chain reaction RT-PCR for tyrosine hydroxylase phosphoglycolate phosphatase PGP 95 and melanoma antigen family A 1 MAGE-1 in blood and bone marrow
II Determine if change from baseline of MRD is associated with event free and overall survival
III Determine whether tumor biology at diagnosis correlates with event-free and overall survival for either of the randomized regimens
IV To explore the relationship between antibody-dependent cellular cytoxicity ADCC and EFS
V To determine a descriptive profile of human anti-chimeric antibody HACA during immunotherapy
VI To determine the variability of 13-cis-retinoic-acid pharmacokinetics and relationship to pharmacogenomic parameters and determine if these levels andor genetic variations correlate with EFS or systemic toxicity
VII To determine the potential effect of ch1418 on cardiac repolarization and to evaluate ch1418 plasma levels
VIII To determine if the presence of naturally occurring anti-glycan antibodies correlates with allergic reactions and blood levels of ch1418
IX To determine if the genotype of Fc receptor FcR and killer cell immunoglobulin-like receptor KirKir-ligand correlate with EFS
X To determine if natural killer cell p30-related protein NKp30 isoform expression and single nucleotide polymorphism SNP and circulating ligand B7-H6 are prognostic of EFS or OS
OUTLINE Patients stratified with biopsy-confirmed post-ASCT persistent disease who are also enrolled on Childrens Oncology Group COG-A3973 or COG-ANBL0532 are assigned to treatment Arm II Patients in the first set of strata are randomized to 1 of 2 treatment arms
ARM I Beginning on day 56-85 post-ASCT patients receive isotretinoin orally PO twice daily BID for 14 days Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity Patients may cross over to Arm II provided they have not experienced disease progression and have not received any further anti-neuroblastoma therapy following completion of isotretinoin therapy closed to accrual as of 4162009
ARM II Beginning on day 56-85 post-ASCT patients receive immunotherapy comprising sargramostim GM-CSF subcutaneously SC or intravenously IV over 2 hours on days 0-13 during courses 1 3 and 5 and dinutuximab IV over 10-20 hours on days 3-6 of courses 1-5 Patients also receive aldesleukin IV continuously on days 0-3 and 7-10 during courses 2 and 4 Immunotherapy repeats every 28 days for 5 courses in the absence of disease progression or unacceptable toxicity Patients also receive isotretinoin as in Arm I beginning on day 11 of immunotherapy
After completion of study treatment patients are followed up periodically for 10 years
I Determine if monoclonal antibody Ch1418 dinutuximab cytokines isotretinoin 13-cis-retinoic acid or RA improves event free survival after myeloablative therapy and stem cell rescue as compared to RA alone in high risk neuroblastoma patients who have achieved a pre-autologous stem cell transplant ASCT response of complete response CR very good partial response VGPR or partial response PR
SECONDARY OBJECTIVES
I Determine if monoclonal antibody Ch1418 cytokines isotretinoin 13-cis-retinoic acid or RA improves overall survival after myeloablative therapy and stem cell rescue as compared to RA alone in high risk neuroblastoma patients who have achieved a pre-ASCT response of CR VGPR or PR
II Determine if immunotherapy RA improves event free survival and overall survival as compared to RA alone in the subgroup of high risk International Neuroblastoma Staging System INSS stage 4 neuroblastoma patients who have achieved a pre-ASCT response of CR VGPR or PR
III Determine the toxicities of the combination of monoclonal antibody Ch1418 with cytokines
IV To compare the outcome data of the patients with persistent disease documented by biopsy Stratum 07 to the historical data for the analogous patients from Childrens Cancer Group CCG-3981
V To further describe and refine the event free survival EFS and overall survival OS estimates and baseline characteristics for subjects receiving Ch1418 cytokines RA following cessation of the randomized portion of the study
VI To further describe the safety and toxicity of Ch1418 cytokines RA under the new administration guidelines implemented following cessation of the randomized portion of the study with focus on a number of courses delivered per subject b number of dose reductions or stoppage ch1418 andor interleukin IL-2 and c number of toxic deaths
TERTIARY OBJECTIVES
I In the subgroup of neuroblastoma patients who have achieved a pre-ASCT response of CR VGPR or PR determine if there is a difference between the two randomized regimens in reducing the minimal residual disease MRD burden as detected by the following parameters meta-iodobenylguanidine MIBG scan immunocytology IC of blood and bone marrow samples reverse transcriptase-polymerase chain reaction RT-PCR for tyrosine hydroxylase phosphoglycolate phosphatase PGP 95 and melanoma antigen family A 1 MAGE-1 in blood and bone marrow
II Determine if change from baseline of MRD is associated with event free and overall survival
III Determine whether tumor biology at diagnosis correlates with event-free and overall survival for either of the randomized regimens
IV To explore the relationship between antibody-dependent cellular cytoxicity ADCC and EFS
V To determine a descriptive profile of human anti-chimeric antibody HACA during immunotherapy
VI To determine the variability of 13-cis-retinoic-acid pharmacokinetics and relationship to pharmacogenomic parameters and determine if these levels andor genetic variations correlate with EFS or systemic toxicity
VII To determine the potential effect of ch1418 on cardiac repolarization and to evaluate ch1418 plasma levels
VIII To determine if the presence of naturally occurring anti-glycan antibodies correlates with allergic reactions and blood levels of ch1418
IX To determine if the genotype of Fc receptor FcR and killer cell immunoglobulin-like receptor KirKir-ligand correlate with EFS
X To determine if natural killer cell p30-related protein NKp30 isoform expression and single nucleotide polymorphism SNP and circulating ligand B7-H6 are prognostic of EFS or OS
OUTLINE Patients stratified with biopsy-confirmed post-ASCT persistent disease who are also enrolled on Childrens Oncology Group COG-A3973 or COG-ANBL0532 are assigned to treatment Arm II Patients in the first set of strata are randomized to 1 of 2 treatment arms
ARM I Beginning on day 56-85 post-ASCT patients receive isotretinoin orally PO twice daily BID for 14 days Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity Patients may cross over to Arm II provided they have not experienced disease progression and have not received any further anti-neuroblastoma therapy following completion of isotretinoin therapy closed to accrual as of 4162009
ARM II Beginning on day 56-85 post-ASCT patients receive immunotherapy comprising sargramostim GM-CSF subcutaneously SC or intravenously IV over 2 hours on days 0-13 during courses 1 3 and 5 and dinutuximab IV over 10-20 hours on days 3-6 of courses 1-5 Patients also receive aldesleukin IV continuously on days 0-3 and 7-10 during courses 2 and 4 Immunotherapy repeats every 28 days for 5 courses in the absence of disease progression or unacceptable toxicity Patients also receive isotretinoin as in Arm I beginning on day 11 of immunotherapy
After completion of study treatment patients are followed up periodically for 10 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| U10CA098543 | NIH | CTEP | httpsreporternihgovquickSearchU10CA098543 |
| NCI-2009-01064 | REGISTRY | None | None |
| s14-01661 | None | None | None |
| COG-ANBL0032 | None | None | None |
| PANBL0032_A33PAMDREVW01 | None | None | None |
| CDR0000069018 | None | None | None |
| ANBL0032 | None | None | None |
| ANBL0032 | OTHER | None | None |
| ANBL0032 | OTHER | None | None |
| U10CA180886 | NIH | None | None |
| U10CA030969 | NIH | None | None |