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
Study Overview
Status
Conditions
Intervention / Treatment
- Drug: Carboplatin
- Drug: Etoposide
- Procedure: Magnetic Resonance Imaging
- Drug: Cisplatin
- Procedure: Biospecimen Collection
- Drug: Cyclophosphamide
- Other: Survey Administration
- Drug: Vincristine
- Radiation: Radiation Therapy
- Drug: Doxorubicin
- Drug: Irinotecan
- Procedure: Computed Tomography
- Drug: Melphalan
- Drug: Topotecan
- Procedure: Bone Marrow Aspiration
- Drug: Isotretinoin
- Drug: Thiotepa
- Biological: Dinutuximab
- Drug: Temozolomide
- Procedure: Bone Marrow Biopsy
- Drug: Dexrazoxane
- Procedure: Bone Scan
- Procedure: FDG-Positron Emission Tomography and Computed Tomography Scan
- Procedure: Hematopoietic Cell Transplantation
- Procedure: Leukapheresis
- Procedure: Tumor Resection
Detailed Description
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. Patients are then randomized to 1 of 2 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 2-4: 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 4 hours on days 1-3 of cycle 3 and vincristine IV on day 1 and dexrazoxane IV over 5-15 minutes, doxorubicin over 15 minutes, and cyclophosphamide over 1 hours on days 1-2 of cycle 4 in the absence of unacceptable toxicity. Patients undergo testing to determine response and proceed to surgery followed by induction cycle 5 or extended induction.
INDUCTION CYCLE 5: Patients receive cisplatin IV over 4 hours and etoposide IV over 2 hours on days 1-3 in the absence of unacceptable toxicity. Patients with a response to therapy proceed to consolidation.
EXTENDED INDUCTION: Patients whose cancer did not respond 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 dinutuximan IV over 10 hours. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Patients receive thiotepa IV over 2 hours on days -7 to -5 and cyclophosphamide IV over 1 hour on days -5 to -2. 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. Patients receive stem cell infusion IV on day 0. Between day +42 and day +80 after second transplant, 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 each cycle. 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.
Patients undergo bone marrow aspiration and/or biopsy, computed tomography (CT) scan, magnetic resonance imaging (MRI), iodine-123 meta-iodobenzylguanidine (I-MIBG) scan and fluorodeoxyglucose position emission tomography (FDG-PET) scan throughout the study.
ARM B:
INDUCTION CYCLES 2-4: 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 4 hours on days 1-3 and dinutuximab IV on days 2-5 on cycle 3 and vincristine IV on day 1 and dexrazoxane IV over 5-15 minutes, doxorubicin over 15 minutes, and cyclophosphamide over 1 hours on days 1-2, and dinutuximab IV over 10 hours on days 2-5 of cycle 4 in the absence of unacceptable toxicity. Patients then undergo testing to determine response and proceed to surgery followed by induction cycle 5 or extended induction.
INDUCTION CYCLE 5: Patients receive cisplatin IV over 4 hours and etoposide IV over 2 hours on days 1-3 and dinutuximab IV on days 2-5 in the absence of unacceptable toxicity. Patients with a response to therapy proceed to consolidation.
EXTENDED INDUCTION: Patients receive temozolomide PO, via NG, or via G-tube on days 1-5, irinotecan IV over 90 minutes on days 1-5, and dinutuximan IV over 10 hours. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity
CONSOLIDATION: Patients receive thiotepa IV over 2 hours on days -7 to -5 and cyclophosphamide IV over 1 hour on days -5 to -2. 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. Patients receive stem cell infusion IV on day 0. Between day +42 and day +80 after second transplant, 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 each cycle. 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.
Patients undergo bone marrow aspiration and/or biopsy, CT scan, MRI, I-MIBG scan and FGD-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.
Study Type
Enrollment (Estimated)
Phase
- Phase 3
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
Accepts Healthy Volunteers
Description
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 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 (eg, 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 derived from the Schwartz formula for estimating glomerular filtration rate (GFR) utilizing child length and stature data published by the CDC or
- a 24-hour urine creatinine clearance ≥ 70 mL/min/1.73 m^2 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 (eg, 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Active Comparator: Arm A (SOC treatment)
See detailed description
|
Given IV
Other Names:
Given IV
Other Names:
Undergo MRI
Other Names:
Given IV
Other Names:
Undergo blood sample collection
Other Names:
Given IV
Other Names:
Ancillary studies
Given IV
Other Names:
Undergo radiation therapy
Other Names:
Given IV
Other Names:
Given IV
Undergo CT scan
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Undergo bone marrow aspiration
Given PO
Other Names:
Given IV
Other Names:
Given PO or via NG or G tube
Other Names:
Undergo bone marrow biopsy
Other Names:
Given IV
Other Names:
Undergo MIBG scan
Other Names:
Undergo FDG PET
Other Names:
Undergo stem cell infusion
Other Names:
Undergo apheresis
Other Names:
Undergo tumor resection surgery
|
|
Experimental: Arm B (Dinutuimab in induction)
See detailed description
|
Given IV
Other Names:
Undergo MRI
Other Names:
Given IV
Other Names:
Undergo blood sample collection
Other Names:
Given IV
Other Names:
Ancillary studies
Given IV
Other Names:
Undergo radiation therapy
Other Names:
Given IV
Other Names:
Given IV
Undergo CT scan
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Undergo bone marrow aspiration
Given PO
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given PO or via NG or G tube
Other Names:
Undergo bone marrow biopsy
Other Names:
Given IV
Other Names:
Undergo MIBG scan
Other Names:
Undergo FDG PET
Other Names:
Undergo stem cell infusion
Other Names:
Undergo tumor resection surgery
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Event free survival (EFS)
Time Frame: From time of randomization to first episode of disease relapse or progression post-randomization, first occurrence of a second malignancy, or death, whichever occurs first, up to 12 years
|
An intent-to-treat log-rank test comparison of EFS starting from the time of randomization between the standard Children's Oncology Group (COG) induction therapy with or without extended Induction (arm A) and induction chemoimmunotherapy (arm B) with or without extended induction arms will be performed.
A final analysis two-sided p-value <0.05 will indicate success.
In addition, a sensitivity analysis will be performed consisting of a log-rank test comparison of EFS starting from the time of randomization between patients treated without dinutuximab during induction or extended induction (patients on arm A with GEIR) versus patients treated with dinutuximab during Induction (arm B) who do not receive extended induction.
|
From time of randomization to first episode of disease relapse or progression post-randomization, first occurrence of a second malignancy, or death, whichever occurs first, up to 12 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
End of induction (EOI) response rate
Time Frame: From randomization to end of extended induction
|
Will be evaluated per the 2017 revised International Neuroblastoma Response Criteria (INRC), with patients categorized as good end of induction response (GEIR) or poor end of induction response (PEIR) and also assigned standard INRC overall EOI response.
Will be assessed with an intent-to-treat log-rank test comparison of overall survival (OS) starting from the time of randomization between the standard COG induction therapy with or without extended induction (arm A) and induction chemoimmunotherapy (arm B) with or without extended induction.
Depending on the sample size, a chi-square or Fisher's exact test will be used to evaluate the difference in EOI response rates in these two arms.
Response will be determined using both the revised INRC and GEIR/PEIR classification.
|
From randomization to end of extended induction
|
|
Overall survival
Time Frame: Time to death, up to 12 years
|
Response rates at the end of extended Induction (defined as the last complete disease evaluation prior to consolidation or removal from protocol therapy), 3-year EFS with 95% confidence interval (CI), and 3-year OS with 95% CI will be calculated for arm A and arm B patients that receive an extended induction regimen with chemoimmunotherapy due to PD or a PEIR to Induction therapy.
Response will be determined using both the revised INRC and GEIR/PEIR classification.
|
Time to death, up to 12 years
|
|
Incidence of adverse events
Time Frame: Up to 12 years
|
Common terminology criteria for adverse events (CTCAE) version (v) 5.0 will be used to tabulate grade ≥ 3 non-hematologic and grade ≥ 4 hematologic toxicities.
Will be compared with a Fisher's exact/chi-square test.
In addition, the rates of grade ≥ 3 non-hematologic and grade ≥ 4 hematologic toxicities experienced during extended induction will be tabulated.
|
Up to 12 years
|
|
GD2 expression
Time Frame: At baseline, end of induction, extended induction, post consolidation, relapse/progression and primary tumor resection
|
Dinutuximab binding to pre-therapy patient tumor samples will be measured and categorized as high or low.
Will evaluate for an association between GD2 binding and event-free survival.
|
At baseline, end of induction, extended induction, post consolidation, relapse/progression and primary tumor resection
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Association between tumor and host factors and outcomes
Time Frame: Up to 12 years
|
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.
|
Up to 12 years
|
|
Circulating biomarkers and markers of minimal residual disease
Time Frame: Up to 12 years
|
Will be assessed by comparing the proportion of patients with detectable vs. non-detectable tumor markers (including circulating tumor deoxyribonucleic acid [ctDNA], circulating free DNA [cfDNA], circulating tumor cells [CTCs], 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 (GEE) as appropriate.
|
Up to 12 years
|
|
Patterns of failure
Time Frame: During induction therapy
|
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.
|
During induction therapy
|
|
Effect of telomere maintenance mechanisms
Time Frame: Up to 12 years
|
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 (mRNA) expression of TERT and analysis of telomeric DNA C-circles: telomerase (TERT) positive, alternative of lengthening of telomeres (ALT) positive, or no identified TMM.
|
Up to 12 years
|
|
Functional and quality of life outcomes
Time Frame: At serial time points during induction, extended induction, post-consolidation, and at the end of therapy
|
we will descriptively summarize and compare the total Memorial Symptom Assessment Scale (MSAS) 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).
|
At serial time points during induction, extended induction, post-consolidation, and at the end of therapy
|
|
Adequacy of diagnostic biopsy specimens
Time Frame: At time of tissue collection
|
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.
|
At time of tissue collection
|
|
Associations between family-reported adverse social determinants of health and both clinical outcomes and biology
Time Frame: Up to 12 years
|
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.
|
Up to 12 years
|
|
Develop and validate deep learning predictors of induction response (imaging objective)
Time Frame: At diagnosis, EOI (pre-consolidation), during extended induction, and end of extended induction (pre-consolidation)
|
Scans will be given as input to a convolutional neural network trained to predict EOI response.
|
At diagnosis, EOI (pre-consolidation), during extended induction, and end of extended induction (pre-consolidation)
|
|
Compare institutional versus central determination of overall response, individual response components, and PEIR and GEIR determination (imaging objective)
Time Frame: Up to 12 years
|
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.
|
Up to 12 years
|
|
Incidence of late toxicities
Time Frame: Up to 12 years
|
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.
|
Up to 12 years
|
|
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
Time Frame: Up to 12 years
|
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 ANBL0532^88 using Gray's test.
|
Up to 12 years
|
|
Post-transplant complications
Time Frame: Up to 100 days post transplant
|
Will be evaluated by calculating the incidence of endothelial injury complications (EICs) and non-relapse mortality (NRM) 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.
|
Up to 100 days post transplant
|
|
Associations between end of induction (EOI) response and individual response components
Time Frame: Up to 12 years
|
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).
|
Up to 12 years
|
|
Changes in image-defined risk factors (IDRF)
Time Frame: Up to 12 years
|
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 and compared between treatment arms A and B with the Wilcoxon rank-sum test.
|
Up to 12 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Sara M Federico, Children's Oncology Group
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroectodermal Tumors, Primitive
- Neuroectodermal Tumors, Primitive, Peripheral
- Neuroblastoma
- Ganglioneuroblastoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Protective Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Cardiotonic Agents
- Dermatologic Agents
- Micronutrients
- Antibiotics, Antineoplastic
- Vitamins
- Keratolytic Agents
- Topoisomerase I Inhibitors
- Cyclophosphamide
- Carboplatin
- Etoposide
- Etoposide phosphate
- Cisplatin
- Temozolomide
- Podophyllotoxin
- Irinotecan
- Melphalan
- Doxorubicin
- Liposomal doxorubicin
- Antibodies, Monoclonal
- Vincristine
- Daunorubicin
- Topotecan
- Thiotepa
- Dinutuximab
- Tretinoin
- Isotretinoin
- Dexrazoxane
- Razoxane
- Mechlorethamine
- Nitrogen Mustard Compounds
- Vitamin A
- 3,6-bis(5-chloro-2-piperidyl)-2,5-piperazinedione
Other Study ID Numbers
- NCI-2023-08530 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- U10CA180886 (U.S. NIH Grant/Contract)
- ANBL2131 (Other Identifier: CTEP)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Neuroblastoma
-
Children's Oncology GroupNational Cancer Institute (NCI)Active, not recruitingStage 4S Neuroblastoma | Ganglioneuroblastoma | Stage 2A Neuroblastoma | Stage 2B Neuroblastoma | Stage 3 Neuroblastoma | Stage 4 Neuroblastoma | Stage 1 Neuroblastoma | Stage 2 NeuroblastomaUnited States, Canada, Australia, New Zealand
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Neuroblastoma | Disseminated Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S NeuroblastomaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)Active, not recruitingLocalized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S Neuroblastoma | Ganglioneuroblastoma | Stage 4 NeuroblastomaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)Active, not recruitingRecurrent Neuroblastoma | Stage 4S Neuroblastoma | Stage 2A Neuroblastoma | Stage 2B Neuroblastoma | Stage 3 Neuroblastoma | Stage 4 NeuroblastomaUnited States, Canada, Australia, New Zealand
-
National Cancer Institute (NCI)Active, not recruitingRecurrent Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S Neuroblastoma | Stage 4 NeuroblastomaUnited States, Canada, Australia, New Zealand, Puerto Rico
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S Neuroblastoma | Stage 4 NeuroblastomaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
-
Children's Oncology GroupNational Cancer Institute (NCI)RecruitingLocalized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S Neuroblastoma | Ganglioneuroblastoma | Stage 4 NeuroblastomaUnited States, Puerto Rico, Canada, Australia, New Zealand, Netherlands, Saudi Arabia, Switzerland
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4 NeuroblastomaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedLocalized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S NeuroblastomaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Neuroblastoma | Disseminated Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Stage 4S NeuroblastomaUnited States
Clinical Trials on Carboplatin
-
Eisai Inc.CompletedCancerUnited States, Austria, India
-
Samyang Biopharmaceuticals CorporationCompleted
-
NHS Greater Glasgow and ClydeCompletedOvarian Cancer | Fallopian Tube Cancer | Primary Peritoneal Cavity CancerUnited Kingdom, Australia, New Zealand
-
Duke UniversityCompletedBrain and Central Nervous System TumorsUnited States, Canada
-
National Cancer Institute (NCI)Children's Oncology GroupCompletedBrain and Central Nervous System TumorsUnited States, Canada, Puerto Rico, Australia, Netherlands, New Zealand, Switzerland
-
All India Institute of Medical Sciences, New DelhiCouncil of Scientific and Industrial Research, IndiaUnknownIntraocular RetinoblastomaIndia
-
National Cancer Institute (NCI)CompletedBreast Cancer | Ovarian CancerUnited States
-
AkesoRecruitingAdvanced Squamous Non Small Cell Lung CancerChina
-
H. Lee Moffitt Cancer Center and Research InstituteNational Cancer Institute (NCI)CompletedUnspecified Adult Solid Tumor, Protocol SpecificUnited States
-
Eli Lilly and CompanyCompletedLung NeoplasmsUnited States