Chemotherapy + Stem Cell Rescue for Neuroblastoma
Recruiting in Palo Alto (17 mi)
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Masonic Cancer Center, University of Minnesota
Disqualifiers: Uncontrolled infection, Inadequate organ function, others
No Placebo Group
Prior Safety Data
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
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
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Trial 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 (Biological)
- Carboplatin (Alkylating agents)
- Cyclophosphamide (Alkylating agents)
- Etoposide (Topoisomerase II inhibitors)
- Granulocyte colony stimulating factor (Biological)
- Melphalan (Alkylating agents)
- Thiotepa (Alkylating agents)
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:
πΊπΈ Approved in United States as Paraplatin for:
- Ovarian cancer
- Testicular cancer
- Lung cancer
- Head and neck cancer
- Brain cancer
πͺπΊ Approved in European Union as Carboplatin for:
- Ovarian cancer
- Small cell lung cancer
π¨π¦ Approved in Canada as Carboplatin for:
- Ovarian cancer
- Small cell lung cancer
- Testicular cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Masonic Cancer Center, University of MinnesotaMinneapolis, MN
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Who Is Running the Clinical Trial?
Masonic Cancer Center, University of MinnesotaLead Sponsor
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]High-dose chemotherapy with haemopoietic stem-cell rescue improves event-free survival in patients with high-risk neuroblastoma; however, which regimen has the greatest patient benefit has not been established. We aimed to assess event-free survival after high-dose chemotherapy with busulfan and melphalan compared with carboplatin, etoposide, and melphalan.
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]Topotecan appears to be relatively unaffected by the most common multidrug resistance mechanisms, may potentiate cytotoxicity of alkylators, has good penetration into the central nervous system, is active against a variety of neoplasms, and has myelosuppression as its paramount toxicity. We present our experience with a myeloablative regimen that includes topotecan. Twenty-one patients with poor-prognosis tumors and intact function of key organs received topotecan 2 mg/m2 by 30-min intravenous (i.v.) infusion on days -8, -7, -6, -5, -4; thiotepa 300 mg/m2 by 3 h i.v. infusion on days -8, -7, -6; and carboplatin by 4 h i.v. infusion on days -5, -4, -3 with a daily dose derived from the pediatric Calvert formula, using a targeted area under the curve of seven mg/ml* min ( approximately 500 mg/m2/day). Stem cell rescue was on day 0. The patients were 1 to 29 (median 4) years old; 18 were in complete remission (CR) and three in partial remission (PR). Early toxicities were severe mucositis and erythema with superficial peeling in all patients and a seizure, hypertension, and renal insufficiency followed by veno-occlusive disease in one patient each. Post-transplant treatment included radiotherapy alone (four patients) or plus biological agents (11 patients with neuroblastoma). With a follow-up of 6+ to 32+ (median 11+) months, event-free survivors include 10/11 neuroblastoma patients (first CR), 4/5 brain tumor patients (second PR or CR), 1/3 patients with metastatic Ewing's sarcoma (first or second CR), and a patient transplanted for multiply recurrent immature ovarian teratoma; a patient with desmoplastic small round-cell tumor (second PR) had progressive disease at 8 months. Favorable results for disease control, manageable toxicity, and the antitumor profiles of topotecan, thiotepa, and carboplatin, support use of this three-drug regimen in the treatment of neuroblastoma and brain tumors; applicability to other tumors is still uncertain.
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]High-dose chemotherapy with autologous stem cell rescue (ASCR) is a key component of high-risk neuroblastoma therapy. Resources required to support patients treated with ASCR conditioning regimens [carboplatin/etoposide/melphalan (CEM) and busulfan/melphalan (BuMel)] have not been directly compared.
Topotecan, thiotepa, and carboplatin for neuroblastoma: failure to prevent relapse in the central nervous system. [2013]We report on a three-drug myeloablative regimen designed to consolidate remission and to prevent central nervous system (CNS) relapse of high-risk neuroblastoma (NB). Sixty-six NB patients received topotecan 2 mg/m2/day, x 4 days; thiotepa 300 mg/m2/day, x 3 days; and carboplatin approximately 500 mg/m2/day, x 3 days. Post-SCT treatments included radiotherapy, immunotherapy, 13-cis-retinoic acid, +/-oral etoposide. Significant nonhematologic toxicities were mucositis and skin-related in all patients, convulsions in three patients, and cardiac failure and venocclusive disease of liver in one patient each. Grade 2 hepatotoxicity led to truncating cytoreduction in two patients; both later relapsed in brain. Among 46 patients transplanted in first complete/very good partial remission (CR/VGPR), event-free survival is 54% (s.e.+/-8%) at 36 months post-SCT; notable events were three non-NB-related deaths (adenovirus on day +9, bowel necrosis at 5 months, multiorgan failure at seven months) and four relapses in brain. Of 12 patients transplanted with evidence of NB, two became long-term event-free survivors and two relapsed in the brain. Of eight patients transplanted in second or greater CR/VGPR, one became a long-term event-free survivor and seven relapsed though not in the CNS. This regimen has manageable toxicity but does not prevent CNS relapse.
[Clinical evaluation of A 1 protocol in advanced neuroblastoma]. [2015]For the purpose of studying clinical evaluation of A 1 protocol for advanced neuroblastoma, chemotherapy with vincristine, cyclophosphamide, THP-adriamycin and cisplatin was performed in 8 pediatric patients with advanced neuroblastoma undergoing second look operation (4) or delayed primary operation (4). Tumor volume measured on CT, histological finding of tumor obtained at operation, blood and urinary tumor marker level were studied.
Pilot study of high-dose vincristine, etoposide, carboplatin and melphalan with autologous bone marrow rescue in advanced neuroblastoma. [2019]The efficacy and toxicity of a high-dose multiagent consolidation regimen, OMEC (vincristine, melphalan, etoposide and carboplatin), with autologous bone marrow rescue was studied in patients with poor-prognosis neuroblastoma, 20 patients were treated with OMEC, 18 after induction chemotherapy and 2 following relapse. All patients received, per m2, vincristine 4 mg, etoposide 1 g, carboplatin 1.0-1.75 g and melphalan 180 mg followed by bone marrow rescue. 4 patients (20%) died of treatment-related complications. Severe gastrointestinal toxicity occurred in all of these patients, and in 75% of patients overall. 1 of 5 patients with evaluable disease achieved complete remission. 13 patients (65%) have relapsed a median of 10 months (range 3-26) after receiving OMEC. Thus, OMEC was not more effective, yet more toxic, than high-dose melphalan given alone, and the use of similar multiagent regimens with overlapping toxicities in advanced neuroblastoma appears inadvisable.
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]The prognosis of resistant or relapsing children with neuroblastoma remains very poor, and the search for new therapies is ongoing. In this analysis, we assessed the toxicity of a treosulfan, melphalan, and thiotepa (TMT) regimen in 17 children with recurrent or refractory neuroblastoma who underwent stem cell transplantation (SCT). For allogeneic SCT, fludarabine and antithymocyte globulin were added. The stem cell source was autologous in 8 patients, haploidentical in 8 patients, and a matched unrelated donor in 1 patient. The reported nonhematologic toxicities included grade 3 mucositis, grade 1 to 3 hypertransaminasemia, and in 3 patients, veno-occlusive disease. No neurologic, cardiac, or dermatologic toxicities were observed. The probability of overall survival (OS) in patients with primary resistance was superior to that in patients with relapsed disease (100% versus 22.6%; P = .046). Post-transplantation dinutuximab beta immunotherapy was associated with superior 5-year OS (66.7% versus 11.4%; P = .0007). The use of an allogeneic donor, previous autologous SCT with busulfan and melphalan, and pretreatment with high-dose metaiodobenzylguanidine therapy demonstrated no effect on outcomes. In 4 patients, TMT megatherapy alone was enough to achieve complete remission. The TMT conditioning regimen was well tolerated in heavily pretreated patients with neuroblastoma. The manageable toxicity and addition of new anticancer drugs with optional post-SCT immunotherapy or chemotherapy support further trials with the TMT regimen in patients with neuroblastoma.
Effect of amifostine on neuroblastoma during high dose chemotherapy: in vivo and in vitro investigations. [2013]Amifostine (Ethyol, WR-2721) has been clinically used in combination with high dose therapy of neuroblastoma stage 4 with melphalan, carboplatin and VP-16 in 14 patients. The amifostine group was compared to a historical control group of 24 comparably-treated patients. There were no significant differences regarding the time of hematological recovery, the duration of hospitalization, the duration of antibiotic treatment and the extent of renal toxicity. However, in contrast to four patients of the control group, no patient in the amifostine group developed such severe mucositis that artificial ventilation became necessary. Pretreatment of neuroblastoma cell lines for 30 minutes with amifostine and the free thiol(WR-1065) did not reduce the cytotoxic effects of melphalan, carboplatin and VP-16. Evidence was obtained that the uptake of the activated thiol could be achieved by a polyamine transporter. Taken together, the data do not support the use of amifostine in high dose chemotherapy of neuroblastoma prior to autologous stem cell transplantation. However, amifostine may be more effective in conventional neuroblastoma therapy where protection of bone marrow stem cells is necessary.
Acute Complications After High-Dose Chemotherapy and Stem-Cell Rescue in Pediatric Patients With High-Risk Neuroblastoma Treated in Countries With Different Resources. [2019]High-dose chemotherapy with autologous stem-cell rescue (SCR) is a key component of high-risk neuroblastoma (HRNB) therapy. Carboplatin, etoposide, and melphalan (CEM) or busulfan and melphalan (Bu/Mel) are the most evaluated, effective high-dose chemotherapy for HRNB on the basis of results from major cooperative group studies. Toxicity profiles vary between these regimens, and practice variation exists regarding the preferred high-dose therapy (HDT). We sought to evaluate the safety of HDT and autologous SCR for HRNB in a resource-limited country (Egypt) compared with the resource-rich United States.
Etoposide and carboplatin in neuroblastoma: a French Society of Pediatric Oncology phase II study. [2017]A phase II study of etoposide (VP 16) and carboplatin (CBDCA) was performed in patients with metastatic neuroblastoma (NB). The aim of the study was to find an alternative treatment for induction with different toxicities than the VP 16/cisplatin (CDDP) combination.
Toxicity of single-day high-dose vincristine, melphalan, etoposide and carboplatin consolidation with autologous bone marrow rescue in advanced neuroblastoma. [2019]16 unselected patients with advanced neuroblastoma were given high-dose consolidation chemotherapy with vincristine, melphalan, etoposide and carboplatin over 5 h followed by autologous bone marrow rescue. 3 patients died from treatment-related toxicity, 2 from disease, 1 is alive with disease and 10 are alive and disease-free a median of 12.5 months (range 2-38 months) after bone marrow rescue. All had bone marrow toxicity, most mucositis and 6 had seizures. Renal failure was unexpectedly severe. In the last 3 patients, administration of carboplatin was delayed by 18 h in an attempt to reduce renal damage. The results show that this regimen produces significant morbidity and has a high mortality. Although the overall outcome is encouraging, too few patients have been studied to gauge its efficacy. Whether such aggressive consolidation is necessary in heavily pretreated children with neuroblastoma remains unknown.