Ignite Creation Date:
2024-05-06 @ 3:47 PM
Last Modification Date:
2024-10-26 @ 1:56 PM
Study NCT ID:
NCT04751383
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-07-11
First Post:
2021-02-11
Brief Title:
Testing the Combination of Two Immunotherapy Drugs Magrolimab and Dinutuximab in Patients With Relapsed or Refractory Neuroblastoma or Relapsed Osteosarcoma
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
Phase 1 Trial of Hu5F9-G4 Magrolimab Combined With Dinutuximab in Children and Young Adults With Relapsed and Refractory Neuroblastoma or Relapsed Osteosarcoma
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 phase I trial is to find out the best dose possible benefits andor side effects of magrolimab in combination with dinutuximab in treating patients with neuroblastoma that has come back relapsed or does not respond to treatment refractory or relapsed osteosarcoma Magrolimab and dinutuximab are monoclonal antibodies that may interfere with the ability of tumor cells to grow and spread The combination of magrolimab and dinutuximab may shrink or stabilize relapsed or refractory neuroblastoma or relapsed osteosarcoma In addition this trial may help researchers find out if it is safe to give magrolimab and dinutuximab after surgery to remove tumors from the lungs
Detailed Description:
PRIMARY OBJECTIVES
I Determine the safety and tolerability of Hu5F9-G4 magrolimab in combination with dinutuximab in children and young adults with relapsedrefractory RR neuroblastoma NBL or relapsed osteosarcoma
II Determine the recommended phase 2 dose RP2D of Hu5F9-G4 magrolimab given in combination with dinutuximab in children and young adults
III Determine the safety and feasibility of administering Hu5F9-G4 magrolimab in combination with dinutuximab to patients that undergo pulmonary resection of metastatic osteosarcoma within three weeks of surgery
SECONDARY OBJECTIVES
I Determine the pharmacokinetics PK of Hu5F9-G4 magrolimab in children and young adults
II Evaluate the event free survival EFS in two cohorts of patients who are treated at the recommended phase 2 dose RP2D measurable relapsed osteosarcoma and patients with pulmonary relapse undergoing resection and compare to historical controls
III Observe and record anti-tumor activity IV Evaluate the overall response rate ORR of patients in the NBL cohorts measurable RR NBL and evaluable RR NBL and osteosarcoma patients measurable relapsed osteosarcoma in the expansion cohorts treated at the RP2D
EXPLORATORY OBJECTIVES
I To explore biomarkers of response and resistance including genomic CD47 expression Fc receptor FcR polymorphisms SIRPa polymorphisms and KiR phenotype and immunologic dinutuximab human anti-chimeric antibody HACA magrolimab anti-drug antibody ADA peripheral and bone marrow immune subsets and circulating cytokines
II To explore biomarkers of response in the tumor microenvironment through multiplexed ion beam imaging MIBI on resected tissue or archival tissues including comparison of pre- and post- treatment tumor tissues from patients undergoing staged resection of pulmonary osteosarcoma
OUTLINE This is a dose de-escalation study of magrolimab with fixed-dose dinutuximab followed by a dose-expansion study Patients are assigned to 1 of 2 arms
ARM A Patients receive magrolimab intravenously IV and dinutuximab IV on study Patients also undergo computed tomography CT magnetic resonance imaging MRI and blood sample collection on study as well as bone marrow aspiration and biopsy throughout the trial
ARM B Patients receive magrolimab IV and dinutuximab IV on study Patients with pulmonary osteosarcoma may undergo surgical resection of tumor after cycle 1 After surgery these patients continue receiving magrolimab and dinutuximab on study Patients also undergo CT MRI and collection of blood samples on study as well as bone marrow aspiration and biopsy throughout the trial
After completion of study treatment patients are followed up at months 2 4 6 9 and 12 and then yearly until year 5 or until disease progression
I Determine the safety and tolerability of Hu5F9-G4 magrolimab in combination with dinutuximab in children and young adults with relapsedrefractory RR neuroblastoma NBL or relapsed osteosarcoma
II Determine the recommended phase 2 dose RP2D of Hu5F9-G4 magrolimab given in combination with dinutuximab in children and young adults
III Determine the safety and feasibility of administering Hu5F9-G4 magrolimab in combination with dinutuximab to patients that undergo pulmonary resection of metastatic osteosarcoma within three weeks of surgery
SECONDARY OBJECTIVES
I Determine the pharmacokinetics PK of Hu5F9-G4 magrolimab in children and young adults
II Evaluate the event free survival EFS in two cohorts of patients who are treated at the recommended phase 2 dose RP2D measurable relapsed osteosarcoma and patients with pulmonary relapse undergoing resection and compare to historical controls
III Observe and record anti-tumor activity IV Evaluate the overall response rate ORR of patients in the NBL cohorts measurable RR NBL and evaluable RR NBL and osteosarcoma patients measurable relapsed osteosarcoma in the expansion cohorts treated at the RP2D
EXPLORATORY OBJECTIVES
I To explore biomarkers of response and resistance including genomic CD47 expression Fc receptor FcR polymorphisms SIRPa polymorphisms and KiR phenotype and immunologic dinutuximab human anti-chimeric antibody HACA magrolimab anti-drug antibody ADA peripheral and bone marrow immune subsets and circulating cytokines
II To explore biomarkers of response in the tumor microenvironment through multiplexed ion beam imaging MIBI on resected tissue or archival tissues including comparison of pre- and post- treatment tumor tissues from patients undergoing staged resection of pulmonary osteosarcoma
OUTLINE This is a dose de-escalation study of magrolimab with fixed-dose dinutuximab followed by a dose-expansion study Patients are assigned to 1 of 2 arms
ARM A Patients receive magrolimab intravenously IV and dinutuximab IV on study Patients also undergo computed tomography CT magnetic resonance imaging MRI and blood sample collection on study as well as bone marrow aspiration and biopsy throughout the trial
ARM B Patients receive magrolimab IV and dinutuximab IV on study Patients with pulmonary osteosarcoma may undergo surgical resection of tumor after cycle 1 After surgery these patients continue receiving magrolimab and dinutuximab on study Patients also undergo CT MRI and collection of blood samples on study as well as bone marrow aspiration and biopsy throughout the trial
After completion of study treatment patients are followed up at months 2 4 6 9 and 12 and then yearly until year 5 or until disease progression
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
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 |
|---|---|---|---|
| UM1CA228823 | NIH | CTEP | httpsreporternihgovquickSearchUM1CA228823 |
| NCI-2021-00913 | REGISTRY | None | None |
| PED-CITN-03 | OTHER | None | None |
| PED-CITN-03 | OTHER | None | None |
| P30CA015704 | NIH | None | None |
| U01CA154967 | NIH | None | None |