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

מגייסמקבל משתתפים כעת, לפי רשומת המרשם.

יצירת קשר עם המחקר

בקצרה

שלב 3דרושים 478 משתתפים179 אתרים5 מדינות

קטגוריות

אונקולוגיה86%אימונולוגיה וראומטולוגיה14%

רשום במרשם אחד

ClinicalTrials.govNCT06172296פתיחת רשומה זו ב־ClinicalTrials.govסונכרן לפני 3 ימים

מחקר יחיד יכול להיות רשום בכמה מרשמים. אנו מציגים אותו פעם אחת ומקשרים לכל רשומה שברשותנו.

מידע הניסוי מוצג כפי שפורסם על ידי המרשם, בשפת המקור שלו.

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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.

תקציר

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.

מצבים רפואיים

Ganglioneuroblastoma, Nodular
Neuroblastoma

זכאות

זכאות
מין	הכול
גילאים	ללא מינימום – 30 Years
מתנדבים בריאים	לא

זכאות כפי שנכתבה במרשם

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

זכאות במשפטים פשוטים

הקריטריונים של רשומה זו טרם פורקו למשפטים נפרדים. טקסט המרשם שלמעלה שלם והוא הגרסה המחייבת.

תכנון המחקר

תכנון המחקר
סוג המחקר	התערבותי
שלב	שלב 3
הקצאה	אקראי
מודל ההתערבות	PARALLEL
מטרה ראשית	TREATMENT
הסתרה	NONE (0)
גיוס	דרושים 478 משתתפים

נותן חסות ושותפים

National Cancer Institute (NCI) נותן חסות

זרועות והתערבויות

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

התערבויות

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

מדדי תוצאה

מדד תוצאה ראשוני
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.
מסגרת זמן Up to 3 years
מדד תוצאה משני
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)
מסגרת זמן From randomization to end of extended Induction, up to 12 months
מדד תוצאה משני
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.
מסגרת זמן Up to 3 years
מדד תוצאה משני
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.
מסגרת זמן Up to 2 years
מדד תוצאה משני
GD2 expression
Dinutuximab binding to pre-therapy patient tumor samples will be measured and categorized as high or low.
מסגרת זמן Up to 12 months
מדד תוצאה אחר
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.
מסגרת זמן Up to 10 years
מדד תוצאה אחר
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.
מסגרת זמן Up to 10 years
מדד תוצאה אחר
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.
מסגרת זמן Up to 10 years
מדד תוצאה אחר
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.
מסגרת זמן Up to 10 years
מדד תוצאה אחר
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).
מסגרת זמן At serial time points during Induction, Extended Induction, Post-Consolidation, and at the end of therapy
מדד תוצאה אחר
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.
מסגרת זמן At time of tissue collection
מדד תוצאה אחר
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.
מסגרת זמן Up to 10 years
מדד תוצאה אחר
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.
מסגרת זמן At diagnosis, EOI, during Extended Induction, and end of Extended Induction
מדד תוצאה אחר
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.
מסגרת זמן Up to 10 years
מדד תוצאה אחר
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.
מסגרת זמן Up to 10 years
מדד תוצאה אחר
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.
מסגרת זמן Up to 10 years
מדד תוצאה אחר
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.
מסגרת זמן Up to 100 days post-transplant
מדד תוצאה אחר
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).
מסגרת זמן Up to 10 years
מדד תוצאה אחר
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.
מסגרת זמן Up to 10 years

תאריכים

תאריכים
תאריך התחלה	19 באפריל 2024 (בפועל)
סיום ראשוני	31 בדצמבר 2029 (משוער)
סיום	31 בדצמבר 2029 (משוער)
פורסם לראשונה	15 בדצמבר 2023 (בפועל)
עודכן לאחרונה	17 בספטמבר 2026
התוצאות פורסמו	לא צוין ברשומת המרשם
המצב אומת לאחרונה	אפריל 2026

בפועל פירושו שהאירוע התרחש. משוער פירושו שנותן החסות צופה אותו. שתי המשמעויות שונות זו מזו.

מיקומים

176 אתרים מגייסים

Australia

Australia
מתקן	עיר	מדינה או אזור	מצב
Royal Children's Hospital	Parkville	Victoria	מגייס
Perth Children's Hospital	Perth	Western Australia	מגייס
Sydney Children's Hospital	Randwick	New South Wales	מגייס
Queensland Children's Hospital	South Brisbane	Queensland	מגייס
The Children's Hospital at Westmead	Westmead	New South Wales	מגייס

Canada

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

New Zealand

New Zealand
מתקן	עיר	מדינה או אזור	מצב
Starship Children's Hospital	Grafton	Auckland	מגייס

Puerto Rico

Puerto Rico
מתקן	עיר	מדינה או אזור	מצב
University Pediatric Hospital	San Juan		מגייס

United States

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

129 אתרים נוספים מצוינים ברשומת המרשם.

מסמכי המחקר

לא צורפו מסמכים ברשומת מרשם זו.

שינויים לאורך זמן

10 באוגוסט 2026
אתר נוסף
1 site added (179 total)
178179

מרשם: ClinicalTrials.gov · NCT########

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