Study Results
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View full resultsBasic Information
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ACTIVE_NOT_RECRUITING
PHASE2
153 participants
INTERVENTIONAL
2013-07-05
2025-12-31
Brief Summary
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PRIMARY OBJECTIVE:
* To study the efficacy \[response: complete remission + partial remission (CR+PR)\] to two initial courses of cyclophosphamide and topotecan combined with hu14.18K322A (4 doses/course followed by GM-CSF) in previously untreated children with high-risk neuroblastoma.
* To estimate the event-free survival of patients with newly diagnosed high-risk neuroblastoma treated with the addition of hu14.18K322A to treatment.
SECONDARY OBJECTIVES:
* To study the feasibility of delivering hu14.18K322A to 6 cycles induction chemotherapy and describe the antitumor activity (CR+PR) of this 6 course induction therapy.
* To estimate local control and pattern of failure associated with focal intensity modulated or proton beam radiation therapy dose delivery in high-risk abdominal neuroblastoma.
* To describe the tolerability of four doses of hu14.18K322A with allogeneic natural killer (NK) cells from an acceptable parent, in the immediate post-transplant period \[day +2 - +5 after peripheral blood stem cell (PBSC) infusion\] in consenting participants.
* To describe the tolerability of hu14.18K322A with interleukin-2 and GM-CSF as treatment for minimal residual disease (MRD).
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Detailed Description
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1. Screening phase: Tests and evaluations will be done before treatment starts.
2. Induction phase: Includes chemotherapy plus hu14.18K322A mAb. Participants will also have surgery during this part of the study to remove as much tumor as possible.
3. Consolidation/Intensification phase: Includes high doses of chemotherapy and blood stem cell transplantation with additional, experimental "minimal residual disease" (MRD) treatment. Participants will also get radiation treatment to all sites of the tumor(s) after recovery from the stem cell transplant.
4. Maintenance/MRD treatment phase: With immune therapy in addition to the standard treatment with the drug isotretinoin.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Treatment
Participants receive IV hu14.18K322A with each course of chemotherapy (cyclophosphamide, topotecan, cyclophosphamide, doxorubicin, vincristine, cisplatin, and etoposide). Mesna will be given prior to and after cyclophosphamide infusion. Peripheral blood stem cell harvest (PBSC) and surgical resection of primary tumor will be performed, if feasible. Intensification therapy includes busulfan, melphalan, and levetiracetam with peripheral blood stem cell transplantation. A course of hu14.18K322A with natural killer cell infusion will be given to consenting participants. Radiation therapy will follow PBSC transplant with the exception of any patient requiring emergent radiotherapy. MRD treatment includes hu14.18K322A, G-CSF, GM-CSF, interleukin-2 and isotretinoin.
Cells for infusion are prepared using the CliniMACS System.
cyclophosphamide
Given intravenously (IV)
topotecan
Given IV
hu14.18K322A
Given IV
peripheral blood stem cell harvest
Following evaluation and approval by a member of the transplant staff and completion of the consent form by the participant, collection of peripheral blood stem cells (PBSC) may take place.
surgical resection
The primary tumor will be resected surgically following two initial courses of chemotherapy, if feasible. Patients who are unable to have their primary tumor resected after the initial two courses of induction chemotherapy will undergo surgery for resection of the primary tumor mass and careful lymph node staging.
cisplatin
Given IV
etoposide
Given IV
doxorubicin
Given IV
vincristine
Given IV
busulfan
Given IV
melphalan
Given IV
peripheral blood stem cell transplantation
Transplantation of previously harvested peripheral blood stem cells.
natural killer cell infusion
Natural killer (NK) cells obtained from a suitable donor will be given together with hu14.18K322A prior to early hematopoietic cell recovery. In the event there is not a suitable parental donor, consenting participants will receive an additional course of hu14.18K322A.
radiation therapy
Radiation therapy to the primary and metastatic disease sites will follow peripheral blood stem cell transplant with the exception of any patient requiring emergent radiotherapy. External beam radiotherapy will be delivered to the primary site and select metastatic and bulky nodal sites.
GM-CSF
Given subcutaneously (SQ)
G-CSF
Given subcutaneously (SQ)
mesna
Given IV
levetiracetam
Given IV
interleukin-2
Given by continuous infusion during MRD maintenance, and SQ during induction.
Isotretinoin
Given orally (PO)
CliniMACS
The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.
Interventions
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cyclophosphamide
Given intravenously (IV)
topotecan
Given IV
hu14.18K322A
Given IV
peripheral blood stem cell harvest
Following evaluation and approval by a member of the transplant staff and completion of the consent form by the participant, collection of peripheral blood stem cells (PBSC) may take place.
surgical resection
The primary tumor will be resected surgically following two initial courses of chemotherapy, if feasible. Patients who are unable to have their primary tumor resected after the initial two courses of induction chemotherapy will undergo surgery for resection of the primary tumor mass and careful lymph node staging.
cisplatin
Given IV
etoposide
Given IV
doxorubicin
Given IV
vincristine
Given IV
busulfan
Given IV
melphalan
Given IV
peripheral blood stem cell transplantation
Transplantation of previously harvested peripheral blood stem cells.
natural killer cell infusion
Natural killer (NK) cells obtained from a suitable donor will be given together with hu14.18K322A prior to early hematopoietic cell recovery. In the event there is not a suitable parental donor, consenting participants will receive an additional course of hu14.18K322A.
radiation therapy
Radiation therapy to the primary and metastatic disease sites will follow peripheral blood stem cell transplant with the exception of any patient requiring emergent radiotherapy. External beam radiotherapy will be delivered to the primary site and select metastatic and bulky nodal sites.
GM-CSF
Given subcutaneously (SQ)
G-CSF
Given subcutaneously (SQ)
mesna
Given IV
levetiracetam
Given IV
interleukin-2
Given by continuous infusion during MRD maintenance, and SQ during induction.
Isotretinoin
Given orally (PO)
CliniMACS
The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Newly diagnosed, advanced stage, high-risk neuroblastoma defined as one of the following:
* Children \< 1 year with International Neuroblastoma Staging System (INSS) stage 2a, 2b, 3, 4 or 4S disease AND MYCN amplification (\>10 copies, or greater than four-fold increase in MYCN signal as compared to reference signal).
* INSS 2a or 2b disease AND MYCN amplification, regardless of age or additional biologic features
* INSS stage 3 AND:
1. MYCN amplification (\>10 copies, or greater than four-fold increase in MYCN signal as compared to reference signal, regardless of age or additional biologic features
2. Age \> 18 months (\> 547 days) with unfavorable pathology, regardless of MYCN status
* INSS stage 4 and:
1. MYCN amplification, regardless of age or additional biologic features
2. Age \> 18 months (\> 547 days) regardless of biologic features
3. Age 12 - 18 months (365 - 547 days) with any of the following three unfavorable biologic features (MYCN amplification, unfavorable pathology and/or DNA index =1) or any biologic feature that is indeterminant/unknown
* Children at least 365 days initially diagnosed with: INSS stage 1, 2, 4S who progressed to a stage 4 without interval chemotherapy.
* Histologic proof of neuroblastoma or positive bone marrow for tumor cells with increased urine catecholamines.
* Adequate renal and hepatic function (serum creatinine \<3 x upper limit of normal for age, AST\< 3 x upper limit of normal).
* No prior therapy, unless an emergency situation requires local tumor treatment (discuss with principal investigator).
* Written, informed consent according to institutional guidelines.
* Potential donor is a biologic parent
* Potential donor is at least 18 years of age.
Exclusion Criteria
* Pregnant or breast feeding (female of child-bearing potential).
* Children with INSS 4 disease, age \<18 months with all 3 favorable biologic features (non-amplified MYCN, favorable pathology and DNA index \>1).
18 Years
ALL
No
Sponsors
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Cookies for Kids' Cancer
OTHER
CURE Childhood Cancer, Inc.
OTHER
St. Jude Children's Research Hospital
OTHER
Responsible Party
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Principal Investigators
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Sara M. Federico, MD
Role: PRINCIPAL_INVESTIGATOR
St. Jude Children's Research Hospital
Locations
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St. Jude Children's Research Hospital
Memphis, Tennessee, United States
Countries
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References
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Furman WL, McCarville B, Shulkin BL, Davidoff A, Krasin M, Hsu CW, Pan H, Wu J, Brennan R, Bishop MW, Helmig S, Stewart E, Navid F, Triplett B, Santana V, Santiago T, Hank JA, Gillies SD, Yu A, Sondel PM, Leung WH, Pappo A, Federico SM. Improved Outcome in Children With Newly Diagnosed High-Risk Neuroblastoma Treated With Chemoimmunotherapy: Updated Results of a Phase II Study Using hu14.18K322A. J Clin Oncol. 2022 Feb 1;40(4):335-344. doi: 10.1200/JCO.21.01375. Epub 2021 Dec 6.
Nguyen R, Sahr N, Sykes A, McCarville MB, Federico SM, Sooter A, Cullins D, Rooney B, Janssen WE, Talleur AC, Triplett BM, Anthony G, Dyer MA, Pappo AS, Leung WH, Furman WL. Longitudinal NK cell kinetics and cytotoxicity in children with neuroblastoma enrolled in a clinical phase II trial. J Immunother Cancer. 2020 Mar;8(1):e000176. doi: 10.1136/jitc-2019-000176.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Document Type: Informed Consent Form
Related Links
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St. Jude Children's Research Hospital
Clinical Trials Open at St. Jude
Other Identifiers
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NB2012
Identifier Type: -
Identifier Source: org_study_id
NCI-2013-00034
Identifier Type: REGISTRY
Identifier Source: secondary_id
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