Reduced Chemotherapy and Monoclonal Antibody Therapy 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: Memorial Sloan Kettering Cancer Center
Disqualifiers: Severe organ dysfunction, Pregnancy, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?The purpose of this study is to find out whether N10 chemotherapy is a safe and effective treatment for children with high-risk neuroblastoma.
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.
What data supports the effectiveness of the drug DANYELZA (naxitamab) for treating neuroblastoma?
Naxitamab, marketed as DANYELZA, has been approved by the FDA for treating high-risk neuroblastoma in patients who have relapsed or have not responded to other treatments. It has shown effectiveness in combination with another drug, granulocyte-macrophage colony-stimulating factor, in improving outcomes for these patients.
12345Is naxitamab safe for use in humans?
Naxitamab, used for treating neuroblastoma, has been shown to be generally safe in humans, with common side effects like pain, rash, and cough being manageable. Serious side effects like capillary leak syndrome and long-term toxicities were not observed in studies, and the treatment is often administered in outpatient settings.
12467What makes the drug DANYELZA unique for treating neuroblastoma?
DANYELZA (naxitamab) is unique because it is a humanized monoclonal antibody that specifically targets the GD2 receptor on neuroblastoma cells, and it can be administered on an outpatient basis, making it more convenient for patients. It is particularly used for high-risk neuroblastoma that has relapsed or is resistant to other treatments, offering a new option for these challenging cases.
13589Eligibility Criteria
This trial is for children with high-risk neuroblastoma. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and may need parental consent.Inclusion Criteria
I have been diagnosed with neuroblastoma based on tests.
Signed informed consent indicating awareness of the investigational nature of this treatment
My cancer is a specific type of neuroblastoma with certain genetic features.
+2 more
Exclusion Criteria
I do not have severe problems with my kidneys, heart, liver, brain, lungs, blood, or stomach.
Inability to comply with protocol requirements
Pregnancy
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Induction Chemotherapy
Participants receive 4 cycles of induction chemotherapy
12 weeks
Monoclonal Antibody-Based Therapy
Participants receive 2 cycles of mAb-based therapy to assess response
6 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests N10 chemotherapy's safety and effectiveness in treating high-risk neuroblastoma in children. It involves a combination of drugs: DANYELZA, Sargramostim, Carboplatin, Irinotecan, Temozolomide, Topotecan, Doxorubicin, Cytoxan (Cyclophosphamide), Ifosfamide, Vincristine and Etoposide.
1Treatment groups
Experimental Treatment
Group I: Participants with NeuroblastomaExperimental Treatment11 Interventions
Participants will receive 4 cycles of induction chemotherapy followed by a response-based intervention.
DANYELZA is already approved in United States for the following indications:
🇺🇸 Approved in United States as DANYELZA for:
- High-risk neuroblastoma in the bone or bone marrow that has come back (relapsed) or that did not respond to previous treatment (refractory), and has shown a partial response, minor response, or stable disease to prior therapy
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Memorial Sloan Kettering Cancer CenterNew York, NY
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Who Is Running the Clinical Trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
References
Outpatient administration of naxitamab in combination with granulocyte-macrophage colony-stimulating factor in patients with refractory and/or relapsed high-risk neuroblastoma: Management of adverse events. [2023]Naxitamab is a humanized GD2-binding monoclonal antibody that received accelerated approval from the U.S. Food and Drug Administration for refractory or relapsed high-risk neuroblastoma limited to bone or bone marrow. Trial 201 (NCT03363373) is an ongoing global clinical trial to evaluate the efficacy and safety of naxitamab in combination with granulocyte-macrophage colony-stimulating factor in this population.
Naxitamab: First Approval. [2021]Naxitamab (DANYELZA®, naxitamab-gqgk) is a humanised (IgG1) anti-GD2 (hu3F8) monoclonal antibody was developed by the Memorial Sloan Kettering Cancer Center (with commercial rights licenced to Y-mAbs therapeutics Inc.) for the treatment of neuroblastoma, osteosarcoma and other GD2-positive cancers. Naxitamab was recently granted accelerated approval by the US FDA for marketing as treatment (in combination with granulocyte-macrophage colony-stimulating factor) for paediatric patients at least one year of age and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow demonstrating a partial response, minor response, or stable disease to prior therapy. This article summarizes the milestones in the development of naxitamab leading to this first approval.
Anti-G(D2) antibody treatment of minimal residual stage 4 neuroblastoma diagnosed at more than 1 year of age. [2020]To eradicate minimal residual disease with anti-G(D2) monoclonal antibody 3F8 in stage 4 neuroblastoma (NB) diagnosed at more than 1 year of age.
Naxitamab combined with granulocyte-macrophage colony-stimulating factor as consolidation for high-risk neuroblastoma patients in complete remission. [2022]Naxitamab is a humanized anti-disialoganglioside (GD2) monoclonal antibody approved for treatment of bone/bone marrow refractory high-risk neuroblastoma (HR-NB). Compassionate use (CU) expanded access program at Hospital Sant Joan de Deu permitted treatment of patients in complete remission (CR). We here report the survival, toxicity, and relapse pattern of patients in first or second CR treated with naxitamab and sargramostim (GM-CSF).
Implementation of immunotherapy into the treatment of neuroblastoma - single center experience with the administration of dinutuximab and management of its adverse effects. [2021]Neuroblastoma is the most common extracranial solid tumour of childhood with extremely heterogeneous bio-logical and clinical behaviour. Despite advances in its treatment, the long-term prognosis of patients with a high-risk and relapsed neuroblastoma remains poor. The implementation of immunotherapy into the treatment protocols has the potential to improve it. Dinutuximab, a chimeric monoclonal antibody, leads to the apoptosis of tumour cells through binding to the GD2 receptor. The article aim is to present the first experience of our centre with dinutuximab treatment.
Early Salvage Chemo-Immunotherapy with Irinotecan, Temozolomide and Naxitamab Plus GM-CSF (HITS) for Patients with Primary Refractory High-Risk Neuroblastoma Provide the Best Chance for Long-Term Outcomes. [2023]Patients with high-risk neuroblastoma (HR-NB) who are unable to achieve a complete response (CR) to induction therapy have worse outcomes. We investigated the combination of humanized anti-GD2 mAb naxitamab (Hu3F8), irinotecan (I), temozolomide (T), and sargramostim (GM-CSF)-HITS-against primary resistant HR-NB. Eligibility criteria included having a measurable chemo-resistant disease at the end of induction (EOI) treatment. Patients were excluded if they had progressive disease (PD) during induction. Prior anti-GD2 mAb and/or I/T therapy was permitted. Each cycle, administered four weeks apart, comprised Irinotecan 50 mg/m2/day intravenously (IV) plus Temozolomide 150 mg/m2/day orally (days 1-5); naxitamab 2.25 mg/kg/day IV on days 2, 4, 8 and 10, (total 9 mg/kg or 270 mg/m2 per cycle), and GM-CSF 250 mg/m2/day subcutaneously was used (days 6-10). Toxicity was measured using CTCAE v4.0 and responses through the modified International Neuroblastoma Response Criteria (INRC). Thirty-four patients (median age at treatment initiation, 4.9 years) received 164 (median 4; 1-12) HITS cycles. Toxicities included myelosuppression and diarrhea, which was expected with I/T, and pain and hypertension, expected with naxitamab. Grade ≥3-related toxicities occurred in 29 (85%) of the 34 patients; treatment was outpatient. The best responses were CR = 29% (n = 10); PR = 3% (n = 1); SD = 53% (n = 18); PD = 5% (n = 5). For cohort 1 (early treatment), the best responses were CR = 47% (n = 8) and SD = 53% (n = 9). In cohort 2 (late treatment), the best responses were CR = 12% (n = 2); PR = 6% (n = 1); SD = 53% (n = 9); and PD = 29% (n = 5). Cohort 1 had a 3-year OS of 84.8% and EFS 54.4%, which are statistically significant improvements (EFS p = 0.0041 and OS p = 0.0037) compared to cohort 2. In conclusion, naxitamab-based chemo-immunotherapy is effective against primary chemo-resistant HR-NB, increasing long-term outcomes when administered early during the course of treatment.
Immunotherapy with anti-GD2 monoclonal antibody in infants with high-risk neuroblastoma. [2022]Anti-GD2 monoclonal antibodies (mAb) improve the prognosis of high-risk neuroblastoma (HR-NB). Worldwide experience almost exclusively involves toddlers and older patients treated after multimodality or second-line therapies, that is, many months postdiagnosis. In contrast, at our center, infants received anti-GD2 mAbs because this immunotherapy started during or immediately after induction chemotherapy. We now report on the feasibility, safety, and long-term survival in this vulnerable age group. Thirty-three HR-NB patients were <19 months old when started on 3F8 (murine mAb; n = 21) or naxitamab (humanized-3F8; n = 12), with 30″ to 90″ intravenous infusions. Patients received analgesics and antihistamines. Common toxicities (pain, urticaria, cough) were manageable, allowing outpatient treatment. Capillary leak, posterior reversible encephalopathy syndrome, and mAb-related long-term toxicities did not occur. Two 3F8 cycles were aborted due to bradycardia (a preexisting condition) and asthmatic symptoms, respectively. One patient received ½ dose of Day 1 naxitamab because of hypotension; full doses were subsequently administered. Post-mAb treatments included chemotherapy, radiotherapy, and anti-NB vaccine. Among 3F8 patients, 17/21 are in complete remission off all treatment at 5.6+ to 24.1+ (median 13.4+) years from diagnosis. Among naxitamab patients, 10/12 remain relapse-free post-mAb at 1.7+ to 4.3+ (median 3.1+) years from diagnosis. Toxicity was similar with short outpatient infusions and matched that observed with these and other anti-GD2 mAbs in older patients. These findings were reassuring given that naxitamab is dosed >2.5× higher (~270 mg/m2 /cycle) than 3F8, dinutuximab, and dinutuximab beta (70-100 mg/m2 /cycle). HR-NB in infants proved to be highly curable.
Improved Outcome in Children With Newly Diagnosed High-Risk Neuroblastoma Treated With Chemoimmunotherapy: Updated Results of a Phase II Study Using hu14.18K322A. [2023]We evaluated whether combining a humanized antidisialoganglioside monoclonal antibody (hu14.18K322A) throughout therapy improves early response and outcomes in children with newly diagnosed high-risk neuroblastoma.
Murine anti-GD2 monoclonal antibody 3F8 combined with granulocyte-macrophage colony-stimulating factor and 13-cis-retinoic acid in high-risk patients with stage 4 neuroblastoma in first remission. [2021]Anti-GD2 monoclonal antibody (MoAb) combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) has shown efficacy against neuroblastoma (NB). Prognostic variables that could influence clinical outcome were explored.