12 Participants Needed

Chemotherapy + Stem Cell Rescue for Neuroblastoma

AG
LB
Overseen ByLisa Burke
Age: < 65
Sex: Any
Trial Phase: Phase 2
Sponsor: Masonic Cancer Center, University of Minnesota
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

This is a phase II single center study to administer two courses of myeloablative consolidation chemotherapy each followed by an autologous peripheral blood stem cell (PBSC) rescue in patients with high-risk neuroblastoma who have completed induction chemotherapy (independent of this study). Ideally, patients should begin consolidation chemotherapy no later than 8 weeks after the start of Induction Cycle #5; however it is strongly recommended to begin consolidation within 4-6 weeks after the start of Induction Cycle #5.

Do I need to stop my current medications for the trial?

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.

What data supports the effectiveness of the treatment for neuroblastoma?

Research shows that high-dose chemotherapy with stem cell rescue, including drugs like carboplatin, etoposide, and melphalan, improves event-free survival in patients with high-risk neuroblastoma. Additionally, a regimen including topotecan, thiotepa, and carboplatin has shown favorable results for disease control in neuroblastoma, although it may not prevent relapse in the central nervous system.12345

Is the combination of chemotherapy and stem cell rescue generally safe for treating neuroblastoma?

The combination of chemotherapy drugs like thiotepa, carboplatin, etoposide, and melphalan with stem cell rescue has been studied for neuroblastoma, showing manageable toxicity but with some severe side effects like mucositis (painful inflammation and ulceration of the mucous membranes lining the digestive tract) and gastrointestinal issues. Some studies reported treatment-related deaths and severe toxicities, indicating that while the regimen can be effective, it also carries significant risks.12678

How does the chemotherapy and stem cell rescue treatment for neuroblastoma differ from other treatments?

This treatment combines high-dose chemotherapy drugs like carboplatin, cyclophosphamide, etoposide, melphalan, and thiotepa with stem cell rescue to help patients recover from the intense treatment. It is unique because it uses a combination of drugs that have different toxicity profiles and aims to improve survival in high-risk neuroblastoma patients, although the best regimen is still being studied.1391011

Research Team

AG

Ashish Gupta, MD, PhD

Principal Investigator

Masonic Cancer Center, University of Minnesota

Eligibility Criteria

This trial is for patients under 30 years old with high-risk neuroblastoma who've finished induction chemotherapy. They should show some response to treatment, have no uncontrolled infections, and enough harvested stem cells for transplants. Participants need good liver, heart, lung, and kidney function and must provide consent.

Inclusion Criteria

I was diagnosed with neuroblastoma before turning 30.
My cancer responded to initial treatment or remained stable.
Hematopoietic Recovery from last induction course of chemotherapy
See 3 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Consolidation Course #1

Participants receive thiotepa and cyclophosphamide followed by a PBSC rescue

4-6 weeks
In-patient stay for chemotherapy and PBSC rescue

Consolidation Course #2

Participants receive melphalan, etoposide, and carboplatin followed by a second PBSC rescue

4-6 weeks
In-patient stay for chemotherapy and PBSC rescue

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Treatment Details

Interventions

  • Autologous Stem Cell Infusion
  • Carboplatin
  • Cyclophosphamide
  • Etoposide
  • Granulocyte colony stimulating factor
  • Melphalan
  • Thiotepa
Trial OverviewThe study tests a two-course myeloablative consolidation therapy followed by autologous stem cell rescue in high-risk neuroblastoma patients post-induction chemotherapy. Drugs used include Carboplatin, Thiotepa, Cyclophosphamide, Melphalan, Etoposide along with stem cell infusion and growth factor support.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Patients Treated for NeuroblastomaExperimental Treatment7 Interventions
Consolidation course #1 consists of thiotepa and cyclophosphamide followed by a PBSC rescue. Consolidation course #2 consists of melphalan, etoposide and carboplatin followed by a second PBSC rescue. Post infusion, patients will receive Granulocyte-Colony Stimulating Factor beginning on Day 0 of each consolidation course.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

🇺🇸
Approved in United States as Paraplatin for:
  • Ovarian cancer
  • Testicular cancer
  • Lung cancer
  • Head and neck cancer
  • Brain cancer
🇪🇺
Approved in European Union as Carboplatin for:
  • Ovarian cancer
  • Small cell lung cancer
🇨🇦
Approved in Canada as Carboplatin for:
  • Ovarian cancer
  • Small cell lung cancer
  • Testicular cancer

Find a Clinic Near You

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials
285
Recruited
15,700+

Findings from Research

In a study involving 1347 patients with high-risk neuroblastoma, the high-dose chemotherapy regimen of busulfan and melphalan resulted in a significantly better 3-year event-free survival rate of 50% compared to 38% for the carboplatin, etoposide, and melphalan regimen.
The busulfan and melphalan treatment also led to fewer severe adverse events, with only 4% of patients experiencing life-threatening toxicities, compared to 10% in the carboplatin, etoposide, and melphalan group, suggesting it is a safer option for patients.
Busulfan and melphalan versus carboplatin, etoposide, and melphalan as high-dose chemotherapy for high-risk neuroblastoma (HR-NBL1/SIOPEN): an international, randomised, multi-arm, open-label, phase 3 trial.Ladenstein, R., Pötschger, U., Pearson, ADJ., et al.[2022]
Topotecan, used in a myeloablative regimen with thiotepa and carboplatin, showed promising efficacy in treating poor-prognosis tumors, particularly in neuroblastoma and brain tumors, with a follow-up of up to 32 months revealing significant event-free survival rates.
The treatment was associated with manageable toxicities, although severe mucositis and other complications were noted, indicating that while the regimen is effective, careful monitoring for side effects is necessary.
Topotecan combined with myeloablative doses of thiotepa and carboplatin for neuroblastoma, brain tumors, and other poor-risk solid tumors in children and young adults.Kushner, BH., Cheung, NK., Kramer, K., et al.[2013]
In a study of high-risk neuroblastoma patients undergoing autologous stem cell rescue, those treated with the carboplatin/etoposide/melphalan (CEM) regimen required longer use of antibiotics, antihypertensives, and analgesics compared to those treated with busulfan/melphalan (BuMel).
Patients receiving BuMel had a longer median hospitalization duration and a higher incidence of mechanical ventilation and sinusoidal obstruction syndrome (SOS), indicating that while CEM may require more supportive care resources, BuMel may lead to more severe complications.
Resource Utilization and Toxicities After Carboplatin/Etoposide/Melphalan and Busulfan/Melphalan for Autologous Stem Cell Rescue in High-Risk Neuroblastoma Using a National Administrative Database.Desai, AV., Seif, AE., Li, Y., et al.[2018]

References

Busulfan and melphalan versus carboplatin, etoposide, and melphalan as high-dose chemotherapy for high-risk neuroblastoma (HR-NBL1/SIOPEN): an international, randomised, multi-arm, open-label, phase 3 trial. [2022]
Topotecan combined with myeloablative doses of thiotepa and carboplatin for neuroblastoma, brain tumors, and other poor-risk solid tumors in children and young adults. [2013]
Resource Utilization and Toxicities After Carboplatin/Etoposide/Melphalan and Busulfan/Melphalan for Autologous Stem Cell Rescue in High-Risk Neuroblastoma Using a National Administrative Database. [2018]
Topotecan, thiotepa, and carboplatin for neuroblastoma: failure to prevent relapse in the central nervous system. [2013]
[Clinical evaluation of A 1 protocol in advanced neuroblastoma]. [2015]
Pilot study of high-dose vincristine, etoposide, carboplatin and melphalan with autologous bone marrow rescue in advanced neuroblastoma. [2019]
Feasibility and Safety of Treosulfan, Melphalan, and Thiotepa-Based Megachemotherapy with Autologous or Allogeneic Stem Cell Transplantation in Heavily Pretreated Children with Relapsed or Refractory Neuroblastoma. [2020]
Effect of amifostine on neuroblastoma during high dose chemotherapy: in vivo and in vitro investigations. [2013]
Acute Complications After High-Dose Chemotherapy and Stem-Cell Rescue in Pediatric Patients With High-Risk Neuroblastoma Treated in Countries With Different Resources. [2019]
10.United Statespubmed.ncbi.nlm.nih.gov
Etoposide and carboplatin in neuroblastoma: a French Society of Pediatric Oncology phase II study. [2017]
Toxicity of single-day high-dose vincristine, melphalan, etoposide and carboplatin consolidation with autologous bone marrow rescue in advanced neuroblastoma. [2019]