Combination Therapy for Neuroblastoma

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: St. Jude Children's Research Hospital

Disqualifiers: Severe systemic disease, Pregnancy, Others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

153 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is the combination therapy for neuroblastoma, including hu14.18K322A, safe for humans?

The research articles do not provide specific safety data for hu14.18K322A or the combination therapy for neuroblastoma. However, cabozantinib, another treatment for relapsed neuroblastoma, was found to have manageable side effects in children, suggesting that some treatments for neuroblastoma can be safe with proper dose adjustments. ^{1 2 3 4 5}

What makes the drug hu14.18K322A unique for treating neuroblastoma?

The drug hu14.18K322A is unique for treating neuroblastoma because it is an immunotherapy that targets a specific molecule on cancer cells, potentially offering a more targeted approach compared to traditional chemotherapy, which can affect both cancerous and healthy cells. ^{5 6 7 8 9}

What is the purpose of this trial?

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).

Research Team

Sara M. Federico, MD

Principal Investigator

St. Jude Children's Research Hospital

Eligibility Criteria

This trial is for children under 19 with high-risk neuroblastoma, a type of cancer. They must have specific stages of the disease and certain genetic features like MYCN amplification. Kids who've had no prior treatment except in emergencies can join. Parents may donate cells if they're over 18. Children with severe diseases or girls who are pregnant can't participate.

Inclusion Criteria

I have been newly diagnosed with advanced, high-risk neuroblastoma.

I am under 19 years old.

My child's cancer progressed to stage 4 without chemotherapy after initial diagnosis.

Exclusion Criteria

My child has a specific stage 4 neuroblastoma.

I do not have any severe or uncontrolled illnesses.

I am currently pregnant or breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction

Participants receive chemotherapy plus hu14.18K322A mAb and undergo surgery to remove as much tumor as possible

24 weeks

Multiple visits (in-person)

Consolidation/Intensification

High doses of chemotherapy and blood stem cell transplantation with additional MRD treatment and radiation therapy

24-26 weeks

Multiple visits (in-person)

Maintenance/MRD treatment

Immune therapy in addition to standard treatment with isotretinoin

8-12 months

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Periodic visits (in-person)

Treatment Details

Interventions

• hu14.18K322A

Trial Overview The trial tests a new antibody called hu14.18K322A combined with chemotherapy to see if it helps kids with neuroblastoma enter remission (disease improvement). It also looks at whether this treatment extends the time patients live without their disease getting worse and how well radiation therapy works on abdominal tumors.

Participant Groups

Group I: Treatment Experimental Treatment 21 Interventions

Participants receive IV hu14.18K322A with each course of chemotherapy (cyclophosphamide, topotecan, cyclophosphamide, doxorubicin, vincristine, cisplatin, and etoposide). Mesna will be given prior to and after cyclophosphamide infusion. Peripheral blood stem cell harvest (PBSC) and surgical resection of primary tumor will be performed, if feasible. Intensification therapy includes busulfan, melphalan, and levetiracetam with peripheral blood stem cell transplantation. A course of hu14.18K322A with natural killer cell infusion will be given to consenting participants. Radiation therapy will follow PBSC transplant with the exception of any patient requiring emergent radiotherapy. MRD treatment includes hu14.18K322A, G-CSF, GM-CSF, interleukin-2 and isotretinoin. Cells for infusion are prepared using the CliniMACS System.

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Cookies for Kids' Cancer

Collaborator

Trials

7

Recruited

360+

CURE Childhood Cancer, Inc.

Collaborator

Trials

5

Recruited

230+

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Molecularly Targeted Therapy for Neuroblastoma. [2020]

2. Japan pubmed.ncbi.nlm.nih.gov

Results of a phase II trial for high-risk neuroblastoma treatment protocol JN-H-07: a report from the Japan Childhood Cancer Group Neuroblastoma Committee (JNBSG). [2020]

3. England pubmed.ncbi.nlm.nih.gov

A phase II study of irinotecan in children with relapsed or refractory neuroblastoma: a European cooperation of the Société Française d'Oncologie Pédiatrique (SFOP) and the United Kingdom Children Cancer Study Group (UKCCSG). [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Cabozantinib for relapsed neuroblastoma: Single institution case series. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Synthetic lethal screen identifies NF-κB as a target for combination therapy with topotecan for patients with neuroblastoma. [2022]

6. China pubmed.ncbi.nlm.nih.gov

[Clinical efficacy of combined therapy in children with stage 4 neuroblastoma]. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Current and future strategies for relapsed neuroblastoma: challenges on the road to precision therapy. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Translational Strategies for Repotrectinib in Neuroblastoma. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Lapatinib potentiates cytotoxicity of YM155 in neuroblastoma via inhibition of the ABCB1 efflux transporter. [2022]