NCT06172296ClinicalTrials.gov

Dinutuximab With Chemotherapy, Surgery and Stem Cell Transplantation for the Treatment of Children With Newly Diagnosed High Risk Neuroblastoma

A Phase 3 Study of Dinutuximab Added to Intensive Multimodal Therapy for Children With Newly Diagnosed High-Risk Neuroblastoma

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Phase 3478 Teilnehmende gesucht179 Studienzentren5 Länder

Kategorien

Onkologie86%Immunologie und Rheumatologie14%

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How this study is set up

The points below are drawn from the public registry record for this study. Each one cites the field or sentence it came from. A dash (—) means the record does not state something — not that it is missing or wrong. Many well-run studies, especially small ones, leave some of these blank.

Present: Registered before enrolment beganFirst posted 2023-12-15; recorded start 2024-04-19
Present: Has a defined primary outcomeA primary outcome measure is listed in the record
Present: The primary outcome states a time frameThe primary outcome measure records a time frame
Present: Participants are randomly assignedAllocation is recorded as randomised
Present: Has a comparison groupThe record lists a placebo or comparator arm, or more than one study arm
Not stated: Open label (no blinding)Masking is recorded as none (open label)
Not stated: An ethics committee is not stated in the registry recordThis registry's ingested record has no ethics-committee field
Not stated: Regulatory oversight (such as an IND or IDE) is not stated in the registry recordThis registry's ingested record has no regulatory-authorisation field
Not stated: A data monitoring committee is not stated in the registry recordThis registry's ingested record has no data-monitoring-committee fieldA data monitoring committee is not required for many smaller studies, and its absence here is not unusual.
Present: No cost to participants is mentioned in the recordChecked the summary, description and eligibility text; no cost-to-participant phrase found
Present: Sponsor has 1548 other studies in this databaseCounted from the lead sponsor named in the record (National Cancer Institute (NCI))
Present: Sponsor has posted results for at least one studyBased on the sponsor’s studies in this database

The record lists 2 conditions.
Lead sponsor type recorded as: US National Institutes of Health.
Intervention regulatory context: investigational, within a phased regulatory pathway.

These are facts from the public registry record, not a judgement about the study. Discuss any trial with your own doctor before taking part.

What these facts mean, and what to ask · ruleset v1

Trial stature

Three independent measures of this study, described from its registry record — not a recommendation about it. A rigorous study by investigators nobody has heard of is better evidence than a weak study led by a famous one. How these are scored.

Methodological rigourSTRONG

A strong methodological design for a phase 3 study, judged from its ClinicalTrials.gov record.

How this score is built

Randomised allocation20/20
Participants are randomly allocated between arms
Blinding0/20
Open-label
Control arm15/15
Active-comparator control arm
Primary-outcome specificity10/10
Named primary outcome with a defined time frame
Endpoint type10/10
Mortality / MACE endpoint (hard clinical outcome)
Multi-centre8/8
Multi-centre: 178 sites
Data monitoring committee0/7
No data monitoring committee stated
Prospective registration5/5
Registered before the study start date
Protocol / SAP posted0/5
No protocol or SAP posted to the registry

ScaleMEDIUM

A medium-sized study, international in scope: 478 participants (target), run at 179 sites, across 5 countries.

How this score is built

Enrolment26/40
478 participants (target)
Site count25/25
178 sites
Country count7/15
5 countries
Planned duration10/10
Planned over about 69 months
Sponsor scale10/10
National Cancer Institute (NCI) has led 1,534 trials in our corpus

Investigator standingUNKNOWN

We have no verifiable track record for the investigator named on this trial. That is common for early-career investigators and for records held outside ClinicalTrials.gov — it is not a negative signal.

How this score is built

Investigator standing0/100
No investigator recorded in the registry for this trial

These describe the registry record only, and today we hold ClinicalTrials.gov data. Absent fields lower a score, and absence often reflects registration practice rather than study quality. A high-stature trial is not necessarily safer or a better choice for you — enrolling in a large definitive trial can mean a higher chance of receiving placebo, while a small early-phase study may be the only route to a new therapy.

Zusammenfassung

This phase III trial tests how well the addition of dinutuximab to Induction chemotherapy along with standard of care surgical resection of the primary tumor, radiation, stem cell transplantation, and immunotherapy works for treating children with newly diagnosed high-risk neuroblastoma. Dinutuximab is a monoclonal antibody that binds to a molecule called GD2, which is found on the surface of neuroblastoma cells, but is not present on many healthy or normal cells in the body. When dinutuximab binds to the neuroblastoma cells, it helps signal the immune system to kill the tumor cells. This helps the cells of the immune system kill the cancer cells, this is a type of immunotherapy. When chemotherapy and immunotherapy are given together, during the same treatment cycle, it is called chemoimmunotherapy. This clinical trial randomly assigns patients to receive either standard chemotherapy and surgery or chemoimmunotherapy (chemotherapy plus dinutuximab) and surgery during Induction therapy. Chemotherapy drugs administered during Induction include, cyclophosphamide, topotecan, cisplatin, etoposide, vincristine, and doxorubicin. These drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing or by stopping them from spreading. Upon completion of 5 cycles of Induction therapy, a disease evaluation is completed to determine how well the treatment worked. If the tumor responds to therapy, patients receive a tandem transplantation with stem cell rescue. If the tumor has little improvement or worsens, patients receive chemoimmunotherapy on Extended Induction. During Extended Induction, dinutuximab is given with irinotecan, temozolomide. Patients with a good response to therapy move on to Consolidation therapy, when very high doses of chemotherapy are given at two separate points to kill any remaining cancer cells. Following, transplant, radiation therapy is given to the site where the cancer originated (primary site) and to any other areas that are still active at the end of Induction. The final stage of therapy is Post-Consolidation. During Post-Consolidation, dinutuximab is given with isotretinoin, with the goal of maintaining the response achieved with the previous therapy. Adding dinutuximab to Induction chemotherapy along with standard of care surgical resection of the primary tumor, radiation, stem cell transplantation, and immunotherapy may be better at treating children with newly diagnosed high-risk neuroblastoma.

PRIMARY OBJECTIVE: I. To determine if the event-free survival (EFS) of patients with newly diagnosed high-risk neuroblastoma assigned to early chemoimmunotherapy during Induction differs from that of patients who are not assigned to treatment that includes early chemoimmunotherapy. SECONDARY OBJECTIVES: I. To determine if early chemoimmunotherapy during Induction therapy improves end of Induction (EOI) response rates and overall survival (OS) for patients with newly diagnosed high-risk neuroblastoma. II. To determine response rates, EFS, and OS following an Extended Induction regimen with chemoimmunotherapy in patients with progressive disease or a poor response to Induction therapy. III. To compare the toxicities experienced by patients treated with chemoimmunotherapy during Induction versus those experienced by patients treated with standard Induction and to describe toxicities experienced during Extended Induction. IV. To determine GD2 expression on tumor tissue and tumor cells in bone marrow and assess for associations with response and outcome. EXPLORATORY OBJECTIVES: I. To describe the association between tumor and host factors and outcomes in patients receiving protocol therapy. II. To evaluate circulating biomarkers and markers of minimal residual disease at baseline and during therapy, and assess for associations with response and outcome. III. To compare patterns of failure between patients treated with and without dinutuximab during induction. IV. To determine the effect of telomere maintenance mechanisms on end of Induction response rates, EFS, and OS. V. To explore the impact of high-risk neuroblastoma (HRNBL) and its therapy, including the addition of dinutuximab to Induction chemotherapy, on functional and quality of life outcomes in patients with HRNBL, as measured by caregiver (parent/legal guardian) and patient questionnaires. VI. To describe the adequacy of diagnostic biopsy specimens, including those obtained by percutaneous core needle biopsy. VII. To explore the associations between family-reported adverse social determinants of health and both clinical outcomes and biology. VIII. To develop and validate deep learning predictors of Induction response based on diagnostic MIBG scans. (Imaging Objective) IX. To compare institutional versus central determination of overall response, individual response components (primary tumor, soft tissue and bone metastatic disease, and bone marrow metastatic disease), and poor end of induction response (PEIR) and good end of induction response (GEIR) determination. (Imaging Objective) X. To describe late toxicities (including impaired organ function, neuropsychiatric toxicity, and incidence of secondary malignancy) in patients treated with dinutuximab during Induction or Extended Induction to late toxicities in patients who have not received dinutuximab during these phases of therapy. XI. To evaluate whether reduced dose radiotherapy to the primary site clinical target volume (CTV) in patients with complete response of the primary site at EOI results in comparable local control relative to historical cohorts. XII. To compare post-transplant complications between treatment arms, and assess for associations with outcome. XIII. To assess for associations between EOI response (including good end of Induction response \[GEIR\] and poor end of Induction response \[PEIR\]) and individual response components (primary tumor, soft tissue and bone metastatic disease, and bone marrow metastatic disease) with outcome (EFS and OS). XIV. To describe and compare the changes in image-defined risk factors (IDRFs) between patients treated with and without dinutuximab during Induction and associate with surgical outcomes and local failure rates following primary tumor resection. XV. To bank serial samples of blood, bone marrow, and tumor tissue for future research. OUTLINE: Patients receive Induction cycle 1 and are then randomized to 1 of 2 treatment arms. INDUCTION CYCLE 1: Patients receive cyclophosphamide intravenously (IV) over 30 minutes and topotecan IV over 30 minutes on days 1-5 in the absence of unacceptable toxicity. ARM A: INDUCTION CYCLES 2-5: Patients receive cyclophosphamide IV over 30 minutes and topotecan IV over 30 minutes on days 1-5 of cycle 2 in the absence of unacceptable toxicity. Patients then undergo stem cell harvest via apheresis. Patients then receive cisplatin IV over 4 hours and etoposide IV over 2 hours on days 1-3 of cycles 3 and 5, and vincristine IV on day 1, doxorubicin IV over 15 minutes, and cyclophosphamide IV over 1 hour on days 1-2 of cycle 4 in the absence of unacceptable toxicity. Patients undergo primary tumor resection after Induction cycle 4 or 5. Following Induction cycle 5, patients undergo testing to determine response to Induction therapy. Patients with a good tumor response proceed to Consolidation, while patients with a poor tumor response proceed to Extended Induction. EXTENDED INDUCTION: Patients with a poor tumor response or progression during Induction receive temozolomide orally (PO), via nasogastric tube (NG), or via gastric tube (G-tube) on days 1-5, irinotecan IV over 90 minutes on days 1-5, and dinutuximab IV over 10 hours. Treatment repeats every 21 days for up to a maximum of 6 cycles in the absence of disease progression or unacceptable toxicity. If at any time during Extended Induction testing shows a good tumor response, patients proceed to Consolidation. If after 6 cycles of Extended Induction or if at any time progression is noted, patients are removed from the study. CONSOLIDATION: Patients undergo two autologous hematopoietic stem cell transplantations (HSCTs) during Consolidation. Patients receive thiotepa IV over 2 hours on days -7 to -5 and cyclophosphamide IV over 1 hour on days -5 to -2 during HSCT 1. Patients then receive stem cell infusion IV on day 0. Between 6 and 10 weeks after stem cell infusion, patients receive melphalan IV over 30 minutes on days -7 to -5, etoposide IV over 24 hours on days -7 to -4, and carboplatin over 24 hours on days -7 to -4 during HSCT 2. Patients receive stem cell infusion IV on day 0. Between day +42 and day +80 after HSCT 2. Patients receive radiation daily for 12 treatments in the absence of disease progression or unacceptable toxicity. POST CONSOLIDATION: Patients receive dinutuximab IV over 10 hours on days 4-7 and isotretinoin PO twice daily (BID) on days 11-24 of cycles 1-5. Treatment repeats every 28 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive isotretinoin PO BID on days 15-28 for 1 additional cycle, cycle 6. Patients undergo blood and urine sample collection, echocardiogram (ECHO) or multigated acquisition scan (MUGA), bone marrow aspiration and/or biopsy, computed tomography (CT) scan, magnetic resonance imaging (MRI), iodine-123 meta-iodobenzylguanidine (I-MIBG) scan and possible fluorodeoxyglucose position emission tomography (FDG-PET) scan throughout the study. ARM B: INDUCTION CYCLES 2-5: Patients receive cyclophosphamide IV over 30 minutes, topotecan IV over 30 minutes on days 1-5, and dinutuximab IV over 10 hours on days 2-5 of cycle 2 in the absence of unacceptable toxicity. Patients then undergo stem cell harvest via apheresis. Patients receive cisplatin IV over 4 hours and etoposide IV over 2 hours on days 1-3 and dinutuximab IV over 10 hours on days 2-5 of cycles 3 and 5, and vincristine IV on day 1, doxorubicin IV over 15 minutes, and cyclophosphamide IV over 1 hour on days 1-2, and dinutuximab IV over 10 hours on days 2-5 of cycle 4 in the absence of unacceptable toxicity. Patients undergo primary tumor resection after Induction cycle 4 or 5. Following Induction cycle 5, patients undergo testing to determine response to Induction therapy. Patients with a good tumor response proceed to Consolidation, while patients with a poor tumor response proceed to Extended Induction. EXTENDED INDUCTION: Patients with a poor tumor response or progression during Induction receive temozolomide PO, via NG tube, or via G-tube on days 1-5, irinotecan IV over 90 minutes on days 1-5, and dinutuximab IV over 10 hours. Treatment repeats every 21 days for up to a maximum of 6 cycles in the absence of disease progression or unacceptable toxicity. If at any time during Extended Induction testing shows a good tumor response, patients proceed to Consolidation. If after 6 cycles of Extended Induction or if at any time progression is noted, patients are removed from the study. CONSOLIDATION: Patients undergo two autologous HSCTs during Consolidation. Patients receive thiotepa IV over 2 hours on days -7 to -5 and cyclophosphamide IV over 1 hour on days -5 to -2 during HSCT 1. Patients then receive stem cell infusion IV on day 0. Between 6 and 10 weeks after stem cell infusion patients receive melphalan IV over 30 minutes on days -7 to -5, etoposide IV over 24 hours on days -7 to -4, and carboplatin over 24 hours on days -7 to -4 during HSCT 2. Patients receive stem cell infusion IV on day 0. Between day +42 and day +80 after HSCT 2, patients receive radiation daily for 12 treatments in the absence of disease progression or unacceptable toxicity. POST CONSOLIDATION: Patients receive dinutuximab IV over 10 hours on days 4-7 and isotretinoin PO BID on days 11-24 of cycles 1-5. Treatment repeats every 28 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive isotretinoin PO BID on days 15-28 for 1 additional cycle, cycle 6. Patients undergo blood and urine sample collection, ECHO or MUGA, bone marrow aspiration and/or biopsy, CT scan, MRI, I-MIBG scan and possible FDG-PET scan throughout the study. After completion of study treatment, patients are followed up at 3, 6, 9,12, 15, 18, 24, 30, 36, 42, 48, 54, and 60 months and then periodically for up to 10 years from enrollment.

Erkrankungen

Ganglioneuroblastoma, Nodular
Neuroblastoma

Eignung

Eignung
Geschlecht	Alle
Alter	Kein Mindestalter – 30 Years
Gesunde Freiwillige	Nein

Eignung im Wortlaut des Registers

Inclusion Criteria: * Patients must be enrolled on APEC14B1 and have consented to testing through the Molecular Characterization Initiative (MCI), prior to enrollment on ANBL2131 * ≤ 30 years at the time of initial diagnosis with high-risk disease * \* Must have a diagnosis of neuroblastoma (NBL) or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamines * Newly diagnosed, high risk neuroblastoma (HRNBL) defined as one of the following: * Any age with International Neuroblastoma Risk Group (INRG) Stage L2, MS, or M and MYCN amplification * Age ≥ 547 days and INRG stage M regardless of biologic features (clinical MYCN testing not required prior to enrollment) * Any age initially diagnosed with INRG Stage L1 MYCN amplified NBL who have progressed to stage M without systemic chemotherapy * Age ≥ 547 days of age initially diagnosed with INRG Stage L1, L2, or MS who have progressed to stage M without systemic chemotherapy (clinical MYCN testing not required prior to enrollment) * Patients must have a body surface area (BSA) ≥ 0.25 m\^2 * No prior anti-cancer therapy except as outlined below: * Patients initially recognized to have high-risk disease treated with topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing, and with consent * Patients observed or treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high-risk disease but subsequently found to meet the criteria * Patients who received localized emergency radiation to sites of life threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis * Human immunodeficiency virus (HIV) -infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial * A serum creatinine based on age/sex as follows: * 1 month to \< 6 months: Male 0.4 mg/dL and female 0.4mg/dL * 6 months to \< 1 year: Male 0.5 mg/dL and female 0.5 mg/dL * 1 to \< 2 years: Male 0.6 mg/dL and female 0.6 mg/dL * 2 to \< 6 years: Male 0.8 mg/dL and female 0.8 mg/dL * 6 to \< 10 years: Male 1 mg/dL and female 1 mg/dL * 10 to \< 13 years: Male 1.2 mg/dL and female 1.2 mg/dL * 13 to \< 16 years: Male 1.5 mg/dL and female 1.4 mg/dL * ≥ 16 years: Male 1.7 mg/dL and female 1.4 mg/dL * The threshold creatinine values were derived from the Schwartz formula for estimating glomerular filtration rate (GFR) utilizing child length and stature data published by the Centers for Disease Control (CDC) * or a 24-hour urine creatinine clearance ≥ 70 mL/min/1.73 m\^2 or * or a GFR ≥ 70 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method or direct small molecule clearance method (iothalamate or other molecule per institutional standard) * Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility * Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age * Serum glutamic pyruvic transaminase (SGPT) (Alanine aminotransferase \[ALT\]) ≤ 10 x ULN\* * Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L * \* Shortening fraction of ≥ 27% by echocardiogram, or * Ejection fraction of ≥ 50% by echocardiogram or radionuclide angiogram * Ability to tolerate Peripheral Blood Stem Cell (PBSC) collection: No known contraindication to PBSC collection. Examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure Exclusion Criteria: * Patients who are 365-546 days of age with INRG Stage M and MYCN non-amplified NBL, irrespective of additional biologic features * Patients ≥ 547 days of age with INRG Stage L2, MYCN non-amplified NBL, regardless of additional biologic features * Patients with known bone marrow failure syndromes * Patients on chronic immunosuppressive medications (e.g., tacrolimus, cyclosporine, corticosteroids) for reasons other than prevention/treatment of allergic reactions and adrenal replacement therapy are not eligible. Topical and inhaled corticosteroids are acceptable * Patients with a primary immunodeficiency syndrome who require ongoing immune globulin replacement therapy * Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required prior to enrollment for female patients of childbearing potential * Lactating females who plan to breastfeed their infants * Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation * All patients and/or their parents or legal guardians must sign a written informed consent * All institutional, food and drug administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Eignung in einfachen Aussagen

Die Kriterien dieses Eintrags wurden noch nicht in einzelne Aussagen aufgeschlüsselt. Der Registertext oben ist vollständig und ist die maßgebliche Fassung.

Studiendesign

Studiendesign
Studientyp	Interventionell
Phase	Phase 3
Zuteilung	Randomisiert
Interventionsmodell	PARALLEL
Primäres Ziel	TREATMENT
Verblindung	NONE (0)
Teilnahme	478 Teilnehmende gesucht

Sponsor und Mitwirkende

National Cancer Institute (NCI) Sponsor

Studienarme und Interventionen

Arm A (SOC treatment)ACTIVE_COMPARATOR
See detailed description
Arm B (Dinutuximab in induction)EXPERIMENTAL
See detailed description

Interventionen

Eingriff Biospecimen Collection
Undergo blood and urine sample collection
Eingriff Bone Marrow Aspiration
Undergo bone marrow aspiration
Eingriff Bone Marrow Biopsy
Undergo bone marrow biopsy
Arzneimittel Carboplatin
Given IV
Arzneimittel Cisplatin
Given IV
Eingriff Computed Tomography
Undergo CT scan
Arzneimittel Cyclophosphamide
Given IV
Biologikum Dinutuximab
Given IV
Arzneimittel Doxorubicin
Given IV
Eingriff Echocardiography Test
Undergo ECHO
Arzneimittel Etoposide
Given IV
Eingriff FDG-Positron Emission Tomography and Computed Tomography Scan
Undergo FDG PET
Eingriff Hematopoietic Cell Transplantation
Undergo stem cell infusion
Arzneimittel Irinotecan
Given IV
Arzneimittel Isotretinoin
Given PO
Eingriff Leukapheresis
Undergo apheresis
Eingriff Magnetic Resonance Imaging
Undergo MRI
Arzneimittel Melphalan
Given IV
Eingriff Multigated Acquisition Scan
Undergo MUGA
Strahlentherapie Radiation Therapy
Undergo radiation therapy
Eingriff Radionuclide Imaging
Undergo I-MIBG scan
Sonstige Survey Administration
Ancillary studies
Arzneimittel Temozolomide
Given PO or via NG or G tube
Arzneimittel Thiotepa
Given IV
Arzneimittel Topotecan
Given IV
Eingriff Tumor Resection
Undergo tumor resection surgery
Arzneimittel Vincristine
Given IV

Endpunkte

Primärer Endpunkt
Event free survival (EFS)
EFS time is calculated from time of randomization to Arms A or B to first episode of disease relapse or progression, second malignancy, or death, or until last contact if no event has occurred.
Zeitrahmen Up to 3 years
Sekundärer Endpunkt
End of Induction (EOI) response rate
The response rate will be calculated among all evaluable patients at end of Induction. Responders are defined as patients who achieve a \>= partial response per the revised 2017 International Neuroblastoma Response Criteria (INRC)
Zeitrahmen From randomization to end of extended Induction, up to 12 months
Sekundärer Endpunkt
Overall survival (OS)
OS time is calculated from time of randomization to Arms A or B until death, or until last contact if patient is alive.
Zeitrahmen Up to 3 years
Sekundärer Endpunkt
Incidence of adverse events
The proportion of patients with at least one grade 3 or higher non-hematologic toxicity or grade 4 or higher hematologic toxicity during protocol therapy, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0, will be reported.
Zeitrahmen Up to 2 years
Sekundärer Endpunkt
GD2 expression
Dinutuximab binding to pre-therapy patient tumor samples will be measured and categorized as high or low.
Zeitrahmen Up to 12 months
Sonstiger Endpunkt
Association between tumor and host factors and outcomes
A series of univariate and multivariate Cox proportional hazards (for EFS and OS) and logistic regression (for responders vs. non-responders) models will be fit for patients in Arms A and B to evaluate the relationship between tumor and host factors (including tumor ALK and other somatic mutations, copy-number aberrations, gene fusions, gene expression, and pathogenic germline variants) and chemo-immunotherapy during Induction with outcome.
Zeitrahmen Up to 10 years
Sonstiger Endpunkt
Circulating biomarkers and markers of minimal residual disease
Will be assessed by comparing the proportion of patients with detectable vs. non-detectable tumor markers (including circulating tumor deoxyribonucleic acid, circulating free DNA, circulating tumor cells, and immune function profiling) between Arms A and B during and after induction and post-consolidation therapy using chi-squared tests at each individual time point, and Cochran's Q across time points to determine if there is a consistent difference in proportions between arms across time. In addition, the tumor markers will be analyzed as continuous variables using longitudinal data analysis methodology such as mixed effects models or generalized estimating equations as appropriate.
Zeitrahmen Up to 10 years
Sonstiger Endpunkt
Patterns of failure
The impact of early or late chemoimmunotherapy during Induction on the probability of the involvement of a specific disease site at first relapse will be evaluated using Fisher's exact test.
Zeitrahmen Up to 10 years
Sonstiger Endpunkt
Effect of telomere maintenance mechanisms
A series of univariate and multivariate Cox proportional hazards (for EFS and OS) and logistic regression (for responders vs. non-responders) models will be fit for patients in arms A and B to evaluate the relationship between telomere maintenance mechanism and chemoimmunotherapy during Induction with outcome. Patients will be classified into 3 groups by telomere maintenance mechanism (TMM) based on messenger ribonucleic acid expression of TERT and analysis of telomeric DNA C-circles: telomerase (TERT) positive, alternative of lengthening of telomeres (ALT) positive, or no identified TMM.
Zeitrahmen Up to 10 years
Sonstiger Endpunkt
Functional and quality of life outcomes
Will descriptively summarize and compare the total Memorial Symptom Assessment Scale scores, total sub-domain scores, and individual symptom scores between patients randomized to receive dinutuximab during Induction (Arm B) to those of patients randomized to standard Induction (Arm A).
Zeitrahmen At serial time points during Induction, Extended Induction, Post-Consolidation, and at the end of therapy
Sonstiger Endpunkt
Adequacy of diagnostic biopsy specimens
Will be evaluated by descriptively comparing the successful delineation of histologic classification, MYCN amplification status, and ALK status via the traditional method of obtaining tissue for diagnosis, open surgical biopsy, versus the less invasive percutaneous core needle biopsy.
Zeitrahmen At time of tissue collection
Sonstiger Endpunkt
Associations between family-reported adverse social determinants of health and both clinical outcomes and biology
Kaplan-Meier curves of EFS and OS will be generated and used to calculate 3-year EFS and OS estimates. Associations between social determinants of health (SDOH) and survival outcomes and time to receipt of dinutuximab will be evaluated with univariate and multivariate Cox proportional hazard models. Log-binomial regression will be used to estimate risk ratios and 95% CI for the occurrence of dinutuximab consent to randomization and therapy receipt by SDOH exposure. Effect modification of outcomes as a function of poverty, stratified by race/ethnicity, will be explored.
Zeitrahmen Up to 10 years
Sonstiger Endpunkt
Develop and validate deep learning predictors of Induction response (imaging objective)
Scans will be given as input to a convolutional neural network trained to predict EOI response.
Zeitrahmen At diagnosis, EOI, during Extended Induction, and end of Extended Induction
Sonstiger Endpunkt
Compare institutional versus central determination of overall response, individual response components, and PEIR and GEIR determination (imaging objective)
Will be assessed by calculating the percentage of patients receiving the same EOI institutional and centrally reviewed determination of overall response, individual response components (primary tumor, soft tissue and bone metastatic disease, and bone marrow metastatic disease), and PEIR and GEIR. In addition, Cohen's kappa will be calculated to evaluate the concordance in each of these response measures.
Zeitrahmen Up to 10 years
Sonstiger Endpunkt
Incidence of late toxicities
Will be addressed by calculating the proportion of treated patients with each late effect, including but not limited to impaired organ function, neuropsychiatric toxicity, and secondary malignancy. A 95% confidence interval will be placed on each proportion.
Zeitrahmen Up to 10 years
Sonstiger Endpunkt
Reduced dose radiotherapy to the primary site clinical target volume (CTV) in patients with complete response of the primary site at EOI results in comparable local control relative to historical cohorts
The cumulative incidence of local progression (CILP) in patients with complete response of the primary site at EOI and GEIR on this study will be compared to the CILP rate of 11.2±1.8% observed on ANBL0532 using Gray's test.
Zeitrahmen Up to 10 years
Sonstiger Endpunkt
Post-transplant complications
Will be evaluated by calculating the incidence of endothelial injury complications and non-relapse mortality within 100 days of transplant, transplant-associated thrombotic microangiopathy (TA-TMA), severe TA-TMA, and sinusoidal obstruction syndrome (SOS) on Arms A and B and comparing between arms with a chi-squared test. The impact of TA-TMA occurrence on the timing or exclusion of subsequent therapy and interventions utilized to treat the TA-TMA, and associations with outcomes (EFS and OS) will be assessed.
Zeitrahmen Up to 100 days post-transplant
Sonstiger Endpunkt
Associations between end of induction (EOI) response and individual response components
Log-rank tests will be used to explore the association between EOI response (using both the revised INRC and GEIR/PEIR classification) and individual response components (primary tumor, soft tissue and bone metastatic disease, and bone marrow metastatic disease) with outcome (EFS and OS).
Zeitrahmen Up to 10 years
Sonstiger Endpunkt
Changes in image-defined risk factors (IDRF)
The proportion of patients in the analytic cohort for whom each particular IDRF and also the presence of any IDRF is absent prior to surgical resection will be computed. McNemar's test for paired observations will be applied to determine whether there is a difference in the proportion of each IDRF and any IDRF present before and after initial therapy, and conditional logistic regression will be used to compare between treatment arms A and B. The IDRF status after initial therapy and whether there has been a change from diagnosis will be associated with surgical outcome (complete vs. incomplete resection, presence or absence of surgical complications) using chi-squared tests, and compared between treatment arms A and B with the Cochran-Mantel-Haenszel test. The association of IDRF status with presence or absence of local failure after primary tumor resection will also be evaluated using a chi-squared test, and compared between treatment arms A and B with the Cochran-Mantel-Haenszel.
Zeitrahmen Up to 10 years

Daten

Daten
Startdatum	19. April 2024 (tatsächlich)
Primärer Abschluss	31. Dezember 2029 (geschätzt)
Abschluss	31. Dezember 2029 (geschätzt)
Erstveröffentlichung	15. Dezember 2023 (tatsächlich)
Zuletzt aktualisiert	17. September 2026
Ergebnisse veröffentlicht	Im Registereintrag nicht angegeben
Status zuletzt bestätigt	April 2026

Tatsächlich bedeutet, dass das Ereignis eingetreten ist. Geschätzt bedeutet, dass der Sponsor es erwartet. Die beiden bedeuten Unterschiedliches.

Standorte

176 Studienzentren rekrutieren

Australia

Australia
Einrichtung	Stadt	Bundesland oder Region	Status
Royal Children's Hospital	Parkville	Victoria	Rekrutiert
Perth Children's Hospital	Perth	Western Australia	Rekrutiert
Sydney Children's Hospital	Randwick	New South Wales	Rekrutiert
Queensland Children's Hospital	South Brisbane	Queensland	Rekrutiert
The Children's Hospital at Westmead	Westmead	New South Wales	Rekrutiert

Canada

Canada
Einrichtung	Stadt	Bundesland oder Region	Status
Alberta Children's Hospital	Calgary	Alberta	Rekrutiert
University of Alberta Hospital	Edmonton	Alberta	Rekrutiert
IWK Health Centre	Halifax	Nova Scotia	Rekrutiert
McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario	Rekrutiert
Children's Hospital	London	Ontario	Rekrutiert
Centre Hospitalier Universitaire Sainte-Justine	Montreal	Quebec	Rekrutiert
The Montreal Children's Hospital of the MUHC	Montreal	Quebec	Rekrutiert
Children's Hospital of Eastern Ontario	Ottawa	Ontario	Rekrutiert
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)	Québec		Rekrutiert
Jim Pattison Children's Hospital	Saskatoon	Saskatchewan	Rekrutiert
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont	Sherbrooke	Quebec	Rekrutiert
Janeway Child Health Centre	St. John's	Newfoundland and Labrador	Rekrutiert
Hospital for Sick Children	Toronto	Ontario	Rekrutiert
British Columbia Children's Hospital	Vancouver	British Columbia	Rekrutiert
CancerCare Manitoba	Winnipeg	Manitoba	Rekrutiert

New Zealand

New Zealand
Einrichtung	Stadt	Bundesland oder Region	Status
Starship Children's Hospital	Grafton	Auckland	Rekrutiert

Puerto Rico

Puerto Rico
Einrichtung	Stadt	Bundesland oder Region	Status
University Pediatric Hospital	San Juan		Rekrutiert

United States

United States
Einrichtung	Stadt	Bundesland oder Region	Status
Children's Hospital Medical Center of Akron	Akron	Ohio	Rekrutiert
Albany Medical Center	Albany	New York	Rekrutiert
University of New Mexico Cancer Center	Albuquerque	New Mexico	Ausgesetzt
Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	Rekrutiert
C S Mott Children's Hospital	Ann Arbor	Michigan	Rekrutiert
Mission Hospital	Asheville	North Carolina	Rekrutiert
Children's Healthcare of Atlanta - Arthur M Blank Hospital	Atlanta	Georgia	Rekrutiert
Children's Hospital Colorado	Aurora	Colorado	Rekrutiert
Dell Children's Medical Center of Central Texas	Austin	Texas	Rekrutiert
University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	Rekrutiert
Sinai Hospital of Baltimore	Baltimore	Maryland	Rekrutiert
Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	Rekrutiert
Eastern Maine Medical Center	Bangor	Maine	Rekrutiert
Walter Reed National Military Medical Center	Bethesda	Maryland	Rekrutiert
Children's Hospital of Alabama	Birmingham	Alabama	Rekrutiert
Massachusetts General Hospital Cancer Center	Boston	Massachusetts	Rekrutiert
Dana-Farber Cancer Institute	Boston	Massachusetts	Rekrutiert
Roswell Park Cancer Institute	Buffalo	New York	Rekrutiert
University of Vermont and State Agricultural College	Burlington	Vermont	Rekrutiert
UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	Rekrutiert
Medical University of South Carolina	Charleston	South Carolina	Rekrutiert
Novant Health Presbyterian Medical Center	Charlotte	North Carolina	Rekrutiert
Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	Rekrutiert
University of Virginia Cancer Center	Charlottesville	Virginia	Rekrutiert
University of Illinois	Chicago	Illinois	Rekrutiert
University of Chicago Comprehensive Cancer Center	Chicago	Illinois	Rekrutiert
Lurie Children's Hospital-Chicago	Chicago	Illinois	Rekrutiert
Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	Rekrutiert

129 weitere Studienzentren sind im Registereintrag aufgeführt.

Studiendokumente

In diesem Registereintrag sind keine Dokumente verlinkt.

Änderungen im Zeitverlauf

10. August 2026
Studienzentrum hinzugefügt
1 site added (179 total)
178179

https://xmedica.io/trials/ctgov/NCT06172296