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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for children with high-risk neuroblastoma, a common childhood cancer. Researchers are testing a combination of chemotherapy and a special antibody, hu14.18K322A, to determine its effectiveness in achieving remission (complete or partial disappearance of cancer). Participants must be newly diagnosed with advanced-stage, high-risk neuroblastoma and have not received prior treatment. The study also examines patient outcomes over time and the treatment's side effects. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important advancements in cancer treatment.

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 there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that hu14.18K322A, when combined with initial chemotherapy, is generally well-tolerated by patients. In a study involving 64 patients, continuous pain relief effectively managed the treatment, indicating that most participants did not experience severe side effects. The treatment is also designed to be less harsh on the body.

These findings suggest that hu14.18K322A can be considered safe for humans, particularly as part of efforts to improve treatments for high-risk neuroblastoma. While no treatment is without risk, evidence supports that hu14.18K322A is generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for neuroblastoma?

Researchers are excited about hu14.18K322A for treating neuroblastoma because it offers a unique approach by combining an antibody with chemotherapy and natural killer cell infusions. This treatment works by targeting a specific protein on cancer cells, potentially enhancing the immune system’s ability to attack the tumor. Additionally, the incorporation of hu14.18K322A with other therapies like interleukin-2 and isotretinoin aims to reduce minimal residual disease, which is a critical concern in preventing relapse. Unlike standard treatments that primarily rely on chemotherapy and radiation, this combination therapy may provide a comprehensive attack on the cancer cells, offering hope for improved outcomes.

What evidence suggests that this combination therapy could be effective for neuroblastoma?

Research has shown that adding hu14.18K322A to initial chemotherapy for high-risk neuroblastoma yields promising results. In this trial, participants will receive hu14.18K322A alongside chemotherapy. Studies have found that this combination significantly improves early response rates, with 66.7% of patients experiencing a reduction in tumor size early on, compared to 39.1% without the antibody. This indicates that more patients saw a decrease in tumor size sooner. Additionally, the treatment reduced tumor sizes in most patients. Overall, these findings suggest that hu14.18K322A, when combined with standard chemotherapy, could be a more effective option for treating neuroblastoma in children. ^{1 2 3 5 6}

Who Is on the Research Team?

Sara M. Federico, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8797508/

Updated Results of a Phase II Study Using hu14.18K322A 18K322A to induction chemotherapy significantly improves early responses in patients with newly diagnosed HR neuroblastoma (66.7% v 39.1%; 95% CI 55.0 to 78.3 v ...

2. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.21.01375

Updated Results of a Phase II Study Using hu14.18K322A Adding hu14.18K322A to induction chemotherapy improved early objective responses, significantly reduced tumor volumes in most patients, improved ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34871104/

Updated Results of a Phase II Study Using hu14.18K322A Adding hu14.18K322A to induction chemotherapy improved early objective responses, significantly reduced tumor volumes in most patients, improved end-of- ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01857934

Therapy for Children With Advanced Stage Neuroblastoma Improved Outcome in Children With Newly Diagnosed High-Risk Neuroblastoma Treated With Chemoimmunotherapy: Updated Results of a Phase II Study Using hu14.

5. aacrjournals.org aacrjournals.org/clincancerres/article/23/21/6441/260123/A-Pilot-Trial-of-Humanized-Anti-GD2-Monoclonal

A Pilot Trial of Humanized Anti-GD2 Monoclonal Antibody ... In conclusion, we demonstrate that hu14.18K322A can be safely combined with three standard neuroblastoma chemotherapeutic regimens, cytokines, and NK cells in ...

6. tandfonline.com tandfonline.com/doi/full/10.1080/19420862.2017.1402997

Full article: Tolerability, response and outcome of high-risk ... Phase I trial of a novel anti-GD2 monoclonal antibody, Hu14.18K322A, designed to decrease toxicity in children with refractory or recurrent neuroblastoma. J ...