Dinutuximab With Chemotherapy, Surgery and Stem Cell Transplantation for the Treatment of Children With Newly Diagnosed High Risk Neuroblastoma

Summary

This phase III trial tests how well the addition of dinutuximab to Induction chemotherapy along with standard of care surgical resection of the primary tumor, radiation, stem cell transplantation, and immunotherapy works for treating children with newly diagnosed high-risk neuroblastoma. Dinutuximab is a monoclonal antibody that binds to a molecule called GD2, which is found on the surface of neuroblastoma cells, but is not present on many healthy or normal cells in the body. When dinutuximab binds to the neuroblastoma cells, it helps signal the immune system to kill the tumor cells. This helps the cells of the immune system kill the cancer cells, this is a type of immunotherapy. When chemotherapy and immunotherapy are given together, during the same treatment cycle, it is called chemoimmunotherapy. This clinical trial randomly assigns patients to receive either standard chemotherapy and surgery or chemoimmunotherapy (chemotherapy plus dinutuximab) and surgery during Induction therapy. Chemotherapy drugs administered during Induction include, cyclophosphamide, topotecan, cisplatin, etoposide, vincristine, and doxorubicin. These drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing or by stopping them from spreading. Upon completion of 5 cycles of Induction therapy, a disease evaluation is completed to determine how well the treatment worked. If the tumor responds to therapy, patients receive a tandem transplantation with stem cell rescue. If the tumor has little improvement or worsens, patients receive chemoimmunotherapy on Extended Induction. During Extended Induction, dinutuximab is given with irinotecan, temozolomide. Patients with a good response to therapy move on to Consolidation therapy, when very high doses of chemotherapy are given at two separate points to kill any remaining cancer cells. Following, transplant, radiation therapy is given to the site where the cancer originated (primary site) and to any other areas that are still active at the end of Induction. The final stage of therapy is Post-Consolidation. During Post-Consolidation, dinutuximab is given with isotretinoin, with the goal of maintaining the response achieved with the previous therapy. Adding dinutuximab to Induction chemotherapy along with standard of care surgical resection of the primary tumor, radiation, stem cell transplantation, and immunotherapy may be better at treating children with newly diagnosed high-risk neuroblastoma.

Conditions

• Ganglioneuroblastoma, Nodular
• Neuroblastoma

Interventions

PROCEDURE

Biospecimen Collection

Undergo blood and urine sample collection

PROCEDURE

Bone Marrow Aspiration

Undergo bone marrow aspiration

PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow biopsy

DRUG

Carboplatin

Given IV

DRUG

Cisplatin

Given IV

PROCEDURE

Computed Tomography

Undergo CT scan

DRUG

Cyclophosphamide

Given IV

BIOLOGICAL

Dinutuximab

Given IV

DRUG

Doxorubicin

Given IV

PROCEDURE

Echocardiography Test

Undergo ECHO

DRUG

Etoposide

Given IV

PROCEDURE

FDG-Positron Emission Tomography and Computed Tomography Scan

Undergo FDG PET

PROCEDURE

Hematopoietic Cell Transplantation

Undergo stem cell infusion

DRUG

Irinotecan

Given IV

DRUG

Isotretinoin

Given PO

PROCEDURE

Leukapheresis

Undergo apheresis

PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

DRUG

Melphalan

Given IV

PROCEDURE

Multigated Acquisition Scan

Undergo MUGA

RADIATION

Radiation Therapy

Undergo radiation therapy

PROCEDURE

Radionuclide Imaging

Undergo I-MIBG scan

OTHER

Survey Administration

Ancillary studies

DRUG

Temozolomide

Given PO or via NG or G tube

DRUG

Thiotepa

Given IV

DRUG

Topotecan

Given IV

PROCEDURE

Tumor Resection

Undergo tumor resection surgery

DRUG

Vincristine

Given IV

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Sara M Federico · Children's Oncology Group

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Max Age

30 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-04-19

Primary Completion

2029-12-31

Completion

2029-12-31

FDA Drug

Yes

Countries

• United States
• Australia
• Canada
• New Zealand
• Puerto Rico

Study Locations