NCT01857934

Therapy for Children With Advanced Stage Neuroblastoma

Neuroblastoma Protocol 2012: Therapy for Children With Advanced Stage High-Risk Neuroblastoma

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 153 (actual)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Neuroblastoma is the most common extracranial solid tumor in childhood, with nearly 50% of patients presenting with widespread metastatic disease. The current treatment for this group of high-risk patients includes intensive multi-agent chemotherapy (induction) followed by myeloablative therapy with stem-cell rescue (consolidation) and then treatment of minimal residual disease (MRD) with isotretinoin. Recently a new standard of care was established by enhancing the treatment of MRD with the addition of a monoclonal antibody (ch14.18) which targets a tumor-associated antigen, the disialoganglioside GD2, which is uniformly expressed by neuroblasts. Despite improvement in 2-year event-free survival (EFS) of 20%, more than one-third of children with high-risk neuroblastoma (HR defined in) still cannot be cured by this approach. Therefore, novel therapeutic approaches are needed for this subset of patients. This study will be a pilot Phase II study of a unique anti-disialoganglioside (anti-GD2) monoclonal antibody (mAb) called hu14.18K322A, given with induction chemotherapy. PRIMARY OBJECTIVE: * To study the efficacy \[response: complete remission + partial remission (CR+PR)\] to two initial courses of cyclophosphamide and topotecan combined with hu14.18K322A (4 doses/course followed by GM-CSF) in previously untreated children with high-risk neuroblastoma. * To estimate the event-free survival of patients with newly diagnosed high-risk neuroblastoma treated with the addition of hu14.18K322A to treatment. SECONDARY OBJECTIVES: * To study the feasibility of delivering hu14.18K322A to 6 cycles induction chemotherapy and describe the antitumor activity (CR+PR) of this 6 course induction therapy. * To estimate local control and pattern of failure associated with focal intensity modulated or proton beam radiation therapy dose delivery in high-risk abdominal neuroblastoma. * To describe the tolerability of four doses of hu14.18K322A with allogeneic natural killer (NK) cells from an acceptable parent, in the immediate post-transplant period \[day +2 - +5 after peripheral blood stem cell (PBSC) infusion\] in consenting participants. * To describe the tolerability of hu14.18K322A with interleukin-2 and GM-CSF as treatment for minimal residual disease (MRD).

Detailed description

The phases of the study are: 1. Screening phase: Tests and evaluations will be done before treatment starts. 2. Induction phase: Includes chemotherapy plus hu14.18K322A mAb. Participants will also have surgery during this part of the study to remove as much tumor as possible. 3. Consolidation/Intensification phase: Includes high doses of chemotherapy and blood stem cell transplantation with additional, experimental "minimal residual disease" (MRD) treatment. Participants will also get radiation treatment to all sites of the tumor(s) after recovery from the stem cell transplant. 4. Maintenance/MRD treatment phase: With immune therapy in addition to the standard treatment with the drug isotretinoin.

Conditions

• Neuroblastoma

Interventions

Type	Name	Description
DRUG	cyclophosphamide	Given intravenously (IV)
DRUG	topotecan	Given IV
BIOLOGICAL	hu14.18K322A	Given IV
PROCEDURE	peripheral blood stem cell harvest	Following evaluation and approval by a member of the transplant staff and completion of the consent form by the participant, collection of peripheral blood stem cells (PBSC) may take place.
PROCEDURE	surgical resection	The primary tumor will be resected surgically following two initial courses of chemotherapy, if feasible. Patients who are unable to have their primary tumor resected after the initial two courses of induction chemotherapy will undergo surgery for resection of the primary tumor mass and careful lymph node staging.
DRUG	cisplatin	Given IV
DRUG	etoposide	Given IV
DRUG	doxorubicin	Given IV
DRUG	vincristine	Given IV
DRUG	busulfan	Given IV
DRUG	melphalan	Given IV
BIOLOGICAL	peripheral blood stem cell transplantation	Transplantation of previously harvested peripheral blood stem cells.
BIOLOGICAL	natural killer cell infusion	Natural killer (NK) cells obtained from a suitable donor will be given together with hu14.18K322A prior to early hematopoietic cell recovery. In the event there is not a suitable parental donor, consenting participants will receive an additional course of hu14.18K322A.
RADIATION	radiation therapy	Radiation therapy to the primary and metastatic disease sites will follow peripheral blood stem cell transplant with the exception of any patient requiring emergent radiotherapy. External beam radiotherapy will be delivered to the primary site and select metastatic and bulky nodal sites.
BIOLOGICAL	GM-CSF	Given subcutaneously (SQ)
BIOLOGICAL	G-CSF	Given subcutaneously (SQ)
DRUG	mesna	Given IV
DRUG	levetiracetam	Given IV
BIOLOGICAL	interleukin-2	Given by continuous infusion during MRD maintenance, and SQ during induction.
DRUG	Isotretinoin	Given orally (PO)
DEVICE	CliniMACS	The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.

Timeline

• Start date: 2013-07-05
• Primary completion: 2021-10-21
• Completion: 2025-12-31
• First posted: 2013-05-20
• Last updated: 2026-04-16
• Results posted: 2023-02-24

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study