Therapy for Children With Advanced Stage Neuroblastoma
Status:
Active, not recruiting
Trial end date:
2023-12-01
Target enrollment:
Participant gender:
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).
Phase:
Phase 2
Details
Lead Sponsor:
St. Jude Children's Research Hospital
Collaborators:
Cookies for Kids' Cancer CURE Childhood Cancer, Inc.