Therapy for Children With Advanced Stage Neuroblastoma

• Status: Active, not recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

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
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: St. Jude Children's Research Hospital
• Collaborators: Cookies for Kids' Cancer; CURE Childhood Cancer, Inc.
• Treatments: Aldesleukin; Antibodies; Antibodies, Monoclonal; Busulfan; Cisplatin; Cyclophosphamide; Dinutuximab; Doxorubicin; Etiracetam; Etoposide; Etoposide phosphate; Immunoglobulins; Interleukin-2; Isotretinoin; Lenograstim; Levetiracetam; Liposomal doxorubicin; Mechlorethamine; Melphalan; Molgramostim; Sargramostim; Topotecan; Vincristine

Criteria

PARTICIPANT Inclusion Criteria:

• Participants <19 years of age (eligible until 19th birthday).

• Newly diagnosed, advanced stage, high-risk neuroblastoma defined as one of the following:

• Children < 1 year with International Neuroblastoma Staging System (INSS) stage 2a, 2b, 3, 4 or 4S disease AND MYCN amplification (>10 copies, or greater than four-fold increase in MYCN signal as compared to reference signal).

• INSS 2a or 2b disease AND MYCN amplification, regardless of age or additional biologic features

• INSS stage 3 AND:

1. MYCN amplification (>10 copies, or greater than four-fold increase in MYCN signal as compared to reference signal, regardless of age or additional biologic features

2. Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN status

• INSS stage 4 and:

1. MYCN amplification, regardless of age or additional biologic features

2. Age > 18 months (> 547 days) regardless of biologic features

3. Age 12 - 18 months (365 - 547 days) with any of the following three unfavorable biologic features (MYCN amplification, unfavorable pathology and/or DNA index =1) or any biologic feature that is indeterminant/unknown

• Children at least 365 days initially diagnosed with: INSS stage 1, 2, 4S who progressed to a stage 4 without interval chemotherapy.

• Histologic proof of neuroblastoma or positive bone marrow for tumor cells with increased urine catecholamines.

• Adequate renal and hepatic function (serum creatinine <3 x upper limit of normal for age, AST< 3 x upper limit of normal).

• No prior therapy, unless an emergency situation requires local tumor treatment (discuss with principal investigator).

• Written, informed consent according to institutional guidelines.

PARTICIPANT Exclusion Criteria:

• Any evidence, as judged by the investigator, of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease).

• Pregnant or breast feeding (female of child-bearing potential).

• Children with INSS 4 disease, age <18 months with all 3 favorable biologic features (non-amplified MYCN, favorable pathology and DNA index >1).

DONOR Inclusion Criteria:

• Potential donor is a biologic parent

• Potential donor is at least 18 years of age.